Cardiovascular Inflammation Reduction Trial "CIRT"

Recruiting

Phase 3 Results N/A

Update History

25 Aug '17
A location was updated in Coral Gables.
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The overall status was updated to "Terminated" at Gonzalez MD & Aswad MD Health Ser.
A location was updated in Cutler Bay.
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The overall status was updated to "Terminated" at American Research Institute, Inc..
A location was updated in Doral.
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The overall status was updated to "Terminated" at Infinite Clinical Research.
A location was updated in Hialeah.
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The overall status was updated to "Terminated" at Qway Research.
A location was updated in Hialeah.
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The overall status was updated to "Terminated" at State of the Art Research.
A location was updated in Hialeah.
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The overall status was updated to "Terminated" at Nova Clinical Research Clinic.
A location was updated in Miami Lakes.
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The overall status was updated to "Terminated" at Veritas Research Corp..
A location was updated in Miami Springs.
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The overall status was updated to "Terminated" at Ocean Blue Medical Research Center.
A location was updated in Miami.
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The overall status was updated to "Terminated" at LG Diagnostics, Inc..
A location was updated in Miami.
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The overall status was updated to "Terminated" at Team Medical Research.
A location was updated in Miami.
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The overall status was updated to "Terminated" at GAD Research Center.
A location was updated in Miami.
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The overall status was updated to "Terminated" at Sanitas Research.
A location was updated in Miami.
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The overall status was updated to "Terminated" at Segui - Med Care Research.
A location was updated in Miami.
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The overall status was updated to "Terminated" at D De La Vega MD Research Group.
A location was updated in Pembroke Pines.
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The overall status was updated to "Terminated" at Broward Research Center.
A location was updated in Pembroke Pines.
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The overall status was updated to "Terminated" at Sandoval - Broward Research Center.
A location was updated in Sweetwater.
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The overall status was updated to "Terminated" at Lenus Research & Medical Group.
14 Jul '17
The Summary of Purpose was updated.
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The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack or multiple coronary blockages. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).
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The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack or multiple coronary blockages. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).
The description was updated.
New
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease in the past will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
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While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease in the past will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
The gender criteria for eligibility was updated to "All."
The eligibility criteria were updated.
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Inclusion Criteria: - Age ≥ 18 years at screening - Documented past history of myocardial infarction OR past evidence of multivessel coronary artery disease by angiography. - To qualify on the basis of past history of myocardial infarction, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be past angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
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Inclusion Criteria: - Age ≥ 18 years at screening - Documented past history of myocardial infarction OR past evidence of multivessel coronary artery disease by angiography. - To qualify on the basis of past history of myocardial infarction, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be past angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
A location was updated in Birmingham.
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The overall status was updated to "Withdrawn" at University of Alabama Birmingham.
A location was updated in Phoenix.
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The overall status was updated to "Withdrawn" at Maricopa Integrated Health System.
A location was updated in Hot Springs.
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The overall status was updated to "Withdrawn" at Michael A. Frais, Cardiologist, P.A..
A location was updated in Monterey.
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The overall status was updated to "Withdrawn" at Central Coast Cardiology.
A location was updated in Moreno Valley.
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The overall status was updated to "Withdrawn" at Spectrum Clinical Research Institute, Inc..
A location was updated in Hialeah.
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The overall status was updated to "Withdrawn" at Diaz - Max. Rehabilitation Center, Inc..
A location was updated in Jacksonville.
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The overall status was updated to "Withdrawn" at Baptist Heart Specialists.
A location was updated in Miami Lakes.
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The overall status was updated to "Withdrawn" at Espinosa - Miami Lakes Research Inc..
A location was updated in Miami.
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The overall status was updated to "Withdrawn" at Gonzalez - Lone Star Research Center.
A location was updated in Miami.
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The overall status was updated to "Withdrawn" at Bioclinical Research Alliance Inc..
A location was updated in Miami.
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The overall status was updated to "Withdrawn" at Garcia - Abel & Buchheim PR, Inc..
A location was updated in Miami.
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The overall status was updated to "Withdrawn" at Cardiovascular Research Center of South Florida.
A location was updated in Tamarac.
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The overall status was updated to "Withdrawn" at Better Care Med of Tamarac.
A location was updated in Virginia Gardens.
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The overall status was updated to "Withdrawn" at Almonte -Virginia Gardens Research.
A location was updated in Conyers.
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The overall status was updated to "Withdrawn" at Rockdale Medical Research Associates.
A location was updated in Valparaiso.
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The overall status was updated to "Withdrawn" at Northwest Indiana Cardiovascular Physicians.
A location was updated in Kansas City.
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The overall status was updated to "Withdrawn" at Saint Luke's Lipid & Diabetes Research.
A location was updated in Lake Success.
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The overall status was updated to "Withdrawn" at ProHealth Care Associates.
A location was updated in Enola.
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The overall status was updated to "Withdrawn" at Gadani Associates.
A location was updated in Channelview.
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The overall status was updated to "Withdrawn" at Willits - Aztec Clinical Research, Inc..
A location was updated in Irving.
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The overall status was updated to "Withdrawn" at Healthcare Associates of Irving.
A location was updated in Pasadena.
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The overall status was updated to "Withdrawn" at Med-Olam Clinical Research, Llc.
A location was updated in Huntington.
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The overall status was updated to "Withdrawn" at Marshall Cardiology.
A location was updated in Toronto.
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The overall status was updated to "Withdrawn" at Women's College Hospital.
25 May '16
A location was updated in Bakersfield.
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The overall status was updated to "Withdrawn" at Central Cardiology Medical Clinic.
A location was updated in Imperial.
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The overall status was updated to "Withdrawn" at Sun Valley Research Center.
A location was updated in Lomita.
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The overall status was updated to "Withdrawn" at Torrance Clinical Research Inc.
A location was updated in Rancho Mirage.
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The overall status was updated to "Withdrawn" at Eisenhower Desert Cardiology Center.
A location was updated in Celebration.
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The overall status was updated to "Withdrawn" at Florida Lung, Asthma and Sleep Specialists.
A location was updated in Fort Myers.
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The overall status was updated to "Withdrawn" at Golden Medical Research, LLC.
A location was updated in Hollywood.
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The overall status was updated to "Withdrawn" at Medical Research Center of Florida.
A location was updated in Miami.
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The overall status was updated to "Withdrawn" at Infinity Research Solutions Inc.
A location was updated in Miami.
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The overall status was updated to "Withdrawn" at A.M. Medical Center & Research.
A location was updated in New Smyma Beach.
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The overall status was updated to "Withdrawn" at Edgewater Medical Research, Inc..
A location was updated in Plantation.
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The overall status was updated to "Withdrawn" at Nova Clinical Research Collaborative.
A location was updated in Plantation.
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The overall status was updated to "Withdrawn" at NOVA Clinical Research Collaborative.
A location was updated in Zephyrhills.
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The overall status was updated to "Withdrawn" at Premier Heart and Vascular Center.
A location was updated in Aurora.
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The overall status was updated to "Withdrawn" at Fox Valley Clinical Research Center.
A location was updated in Peoria.
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The overall status was updated to "Withdrawn" at Unity Point Health CVD Services.
A location was updated in Bossier City.
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The overall status was updated to "Withdrawn" at Grace Research, LLC.
A location was updated in Zachary.
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The overall status was updated to "Withdrawn" at Southern Clinical Research.
A location was updated in Hagerstown.
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The overall status was updated to "Withdrawn" at Hagerstown Heart.
A location was updated in Takoma Park.
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The overall status was updated to "Withdrawn" at Washington Adventist Hospital.
A location was updated in Kansas City.
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The overall status was updated to "Withdrawn" at Truman Medical Center.
A location was updated in Las Vegas.
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The overall status was updated to "Withdrawn" at Accent Clinical Trials.
A location was updated in New York.
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The overall status was updated to "Withdrawn" at Axis Clinical Trials.
A location was updated in New York.
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The overall status was updated to "Withdrawn" at Columbia University Medical Center.
A location was updated in Columbia.
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The overall status was updated to "Withdrawn" at SleepMed of South Carolina.
A location was updated in Dallas.
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The overall status was updated to "Withdrawn" at Dallas Va Medical Center.
A location was updated in Houston.
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The overall status was updated to "Withdrawn" at Cardiology Consultants of Houston.
A location was updated in San Antonio.
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The overall status was updated to "Withdrawn" at Cardiac Research Associates.
A location was updated in San Antonio.
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The overall status was updated to "Withdrawn" at Cardiac Research Associates.
A location was updated in Kelowna.
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The overall status was updated to "Withdrawn" at The Medical Arts Health Research Group.
A location was updated in Fort Erie.
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The overall status was updated to "Withdrawn" at C & L Research.
A location was updated in Hawkesbury.
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The overall status was updated to "Withdrawn" at Source Unique Clinic.
A location was updated in Kitchener.
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The overall status was updated to "Withdrawn" at KMH Cardiology & Diagnostics: Kitchener.
A location was updated in Thornbury.
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The overall status was updated to "Withdrawn" at Blue Mountain Corn Health Center.
17 Nov '15
The description was updated.
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While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease in the past will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
Old
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease in the past will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
The eligibility criteria were updated.
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Inclusion Criteria: - Age ≥ 18 years at screening - Documented past history of myocardial infarction OR past evidence of multivessel coronary artery disease by angiography. - To qualify on the basis of past history of myocardial infarction, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be past angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
Old
Inclusion Criteria: - Age ≥ 18 years at screening - Documented past history of myocardial infarction OR past evidence of multivessel coronary artery disease by angiography. - To qualify on the basis of past history of myocardial infarction, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be past angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
A location was updated in Tucson.
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The overall status was updated to "Withdrawn" at U of Arizona Medical Center South Campus.
A location was updated in Tucson.
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The overall status was updated to "Withdrawn" at University of Arizona Sarver Heart Center.
A location was updated in Beverly Hills.
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The overall status was updated to "Withdrawn" at Ram Dandillaya MD, Inc..
A location was updated in Los Angeles.
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The overall status was updated to "Withdrawn" at Anthony Mills M.D., Inc..
A location was updated in Los Angeles.
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The overall status was updated to "Withdrawn" at Shervin Eshaghian M.D., Inc. (Beverly Hills Cardiology).
A location was updated in Pismo Beach.
New
The overall status was updated to "Withdrawn" at Arroya Medical Group.
A location was updated in Doral.
New
The overall status was updated to "Withdrawn" at Continental Research Corp.
A location was updated in Kissimmee.
New
The overall status was updated to "Withdrawn" at Hope Medical Research.
A location was updated in Port Charlotte.
New
The overall status was updated to "Withdrawn" at Cardiology Associates.
A location was updated in Elizabethtown.
New
The overall status was updated to "Withdrawn" at Krishnan Challappa M.D. PSC.
A location was updated in Mt. Sterling.
New
The overall status was updated to "Withdrawn" at Paul McLaughlin MD.
A location was updated in Annapolis.
New
The overall status was updated to "Withdrawn" at Cardiac Consultants, LLC.
A location was updated in Baltimore.
New
The overall status was updated to "Withdrawn" at Sinai Hospital of Baltimore.
A location was updated in Hattiesburg.
New
The overall status was updated to "Withdrawn" at Hattiesburg Clinic.
A location was updated in Brooklyn.
New
The overall status was updated to "Withdrawn" at R.K. Medical Center.
A location was updated in New York.
New
The overall status was updated to "Withdrawn" at Associate In Internal Medicine Practice.
A location was updated in Pinehurst.
New
The overall status was updated to "Withdrawn" at Pinehurst Medical Clinic, Inc..
A location was updated in Springfield.
New
The overall status was updated to "Withdrawn" at Apex Medical Research, Inc..
A location was updated in Yardley.
New
The overall status was updated to "Withdrawn" at Jeffry A. Lindenbaum DO, PC.
A location was updated in Irmo.
New
The overall status was updated to "Withdrawn" at SC Internal Medicine Associates: Irmo.
A location was updated in Manning.
New
The overall status was updated to "Withdrawn" at Marva D. Williams M.D..
A location was updated in Plano.
New
The overall status was updated to "Withdrawn" at Medical Clinic of North Texas.
A location was updated in Stuart.
New
The overall status was updated to "Withdrawn" at Patrick County Family Practice, PC.
A location was updated in Bolton.
New
The overall status was updated to "Withdrawn" at Goodfellow Medical Centre.
A location was updated in Brampton.
New
The overall status was updated to "Withdrawn" at Wexford Medical Clinic.
A location was updated in Markham.
New
The overall status was updated to "Withdrawn" at Seva Cardiac Centre.
A location was updated in Mississauga.
New
The overall status was updated to "Withdrawn" at Dixie Medical Group.
A location was updated in Windsor.
New
The overall status was updated to "Withdrawn" at Windsor Cardiac Centre.
A location was updated in Saint-Lambert.
New
The overall status was updated to "Withdrawn" at Neufort Inc..
6 Jun '15
A location was updated in Los Angeles.
New
The overall status was updated to "Withdrawn" at Axis Clinical Trials.
A location was updated in Los Angeles.
New
The overall status was updated to "Withdrawn" at Axis Clinical Trials.
A location was updated in National City.
New
The overall status was updated to "Withdrawn" at Albert Sharf, MD.
A location was updated in Wildomar.
New
The overall status was updated to "Withdrawn" at Shiva Heart Center.
A location was updated in Miami.
New
The overall status was updated to "Withdrawn" at Life Spring Research Foundation.
A location was updated in Boise.
New
The overall status was updated to "Withdrawn" at Saint Alphonsus Regional Medical Center.
A location was updated in Hollywood.
New
The overall status was updated to "Withdrawn" at Phillip J. Bean Medical Center.
A location was updated in Pikesville.
New
The overall status was updated to "Withdrawn" at Woodholme Cardiovascular Associates.
A location was updated in Detroit.
New
The overall status was updated to "Withdrawn" at Harris & Associates, PC.
A location was updated in Jersey City.
New
The overall status was updated to "Withdrawn" at Total Cardiology Care, LLC.
A location was updated in Toms River.
New
The overall status was updated to "Withdrawn" at Shore Health Group.
A location was updated in Manhasset.
New
The overall status was updated to "Withdrawn" at Long Island Cardiovascular Consultants.
A location was updated in Washington.
New
The overall status was updated to "Withdrawn" at The Washington Hospital- Cardiovascular Consultants.
A location was updated in West Reading.
New
The overall status was updated to "Withdrawn" at Reading Hospital.
A location was updated in Houston.
New
The overall status was updated to "Withdrawn" at Baylor College of Medicine.
A location was updated in Live Oak.
New
The overall status was updated to "Withdrawn" at Methodist Hospital San Antonio TX.
A location was updated in Southlake.
New
The overall status was updated to "Withdrawn" at Southlake Clinical Trials.
A location was updated in Oshawa.
New
The overall status was updated to "Withdrawn" at King Street Medical Clinic.
A location was updated in Toronto.
New
The overall status was updated to "Withdrawn" at Barbara Erdelyi Medicine Prof Corp.
A location was updated in Mont Royal.
New
The overall status was updated to "Withdrawn" at L'enjeu Medical Center.
A location was updated in Rio Grande.
New
The overall status was updated to "Withdrawn" at Denis Ruiz-Serrano, MD.
25 Nov '14
The description was updated.
New
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past or have angiographically demonstrated multivessel coronary artery disease in the past will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
Old
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past 5 years or have angiographically demonstrated multivessel coronary artery disease in the past five years will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
The eligibility criteria were updated.
New
Inclusion Criteria: - Age ≥ 18 years at screening - Documented past history of myocardial infarction OR past evidence of multivessel coronary artery disease by angiography. - To qualify on the basis of past history of myocardial infarction, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be past angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
Old
Inclusion Criteria: - Age ≥ 18 years at screening - Documented myocardial infarction within the past five years OR evidence of multivessel coronary artery disease by angiography in the past 5 years. - To qualify on the basis of a myocardial infarction in the past 5 years, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be angiographic evidence within the past 5 years of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
14 Nov '13
The Summary of Purpose was updated.
New
The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack or multiple coronary blockages. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).
Old
The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).
The description was updated.
New
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have either suffered documented myocardial infarction in the past 5 years or have angiographically demonstrated multivessel coronary artery disease in the past five years will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
Old
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable post-myocardial infarction patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have suffered documented myocardial infarction in the past five years will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of recurrent myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
The eligibility criteria were updated.
New
Inclusion Criteria: - Age ≥ 18 years at screening - Documented myocardial infarction within the past five years OR evidence of multivessel coronary artery disease by angiography in the past 5 years. - To qualify on the basis of a myocardial infarction in the past 5 years, the event must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - To qualify on the basis of multivessel coronary disease, there must be angiographic evidence within the past 5 years of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis. The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening. - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
Old
Inclusion Criteria: - Age ≥ 18 years at screening - Documented myocardial infarction within the past five years, completed any planned coronary revascularization procedures associated with the qualifying event, and have been clinically stable for at least 60 days prior to screening; the qualifying prior myocardial infarction must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 4,000/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
6 Apr '13
The description was updated.
New
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable post-myocardial infarction patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in (maximum 8 weeks), eligible participants who have suffered documented myocardial infarction in the past five years will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in (maximum 8 weeks) designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of recurrent myocardial infarction, stroke, or cardiovascular death. Secondary and tertiary endpoints include all-cause mortality, coronary revascularization, incident congestive heart failure, incident peripheral artery disease, incident venous thrombosis, clinically significant aortic stenosis, incident atrial fibrillation, incident diabetes among those with metabolic syndrome but not diabetes at study entry, and hemoglobin A1c (HbA1c) control among those with diabetes at study entry. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
Old
While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable post-myocardial infarction patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in, eligible participants who have suffered documented myocardial infarction in the past five years will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of recurrent myocardial infarction, stroke, or cardiovascular death. Secondary endpoints include all-cause mortality, incident diabetes among those with metabolic syndrome at study entry; hemoglobin A1c (HbA1c) control among those with diabetes at study entry; incident venous thrombosis; incident congestive heart failure, and incident atrial fibrillation. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
The eligibility criteria were updated.
New
Inclusion Criteria: - Age ≥ 18 years at screening - Documented myocardial infarction within the past five years, completed any planned coronary revascularization procedures associated with the qualifying event, and have been clinically stable for at least 60 days prior to screening; the qualifying prior myocardial infarction must be documented either by hospital records or by evidence on current ECG of Q waves in two contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar - History of type 2 diabetes or metabolic syndrome at time of study enrollment - Willingness to participate as evidenced by signing the study informed consent Exclusion Criteria: - Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of < 3 years; - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - White blood cell count < 4,000/ul, hematocrit < 32 percent, or platelet count < 75,000/ul - Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN); - Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation; - History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week - Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed. - Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. - Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible; - Current indication for methotrexate therapy; - Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions. - Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol. - New York Heart Association Class IV congestive heart failure.
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Inclusion Criteria: - Documented myocardial infarction within the past five years AND - Type 2 diabetes AND/OR metabolic syndrome - Completed any planned coronary revascularization procedures - Medically stable for at least 60 days prior to screening - Age ≥ 18 years at screening Exclusion Criteria: - Chronic liver disease - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - Chronic infectious disease - Interstitial lung disease or pulmonary fibrosis - Myeloproliferative disease in past 5 years - HIV positive - Requirement for, or intolerance to, methotrexate or folate - History of non-basal cell malignancy or treatment for lymphoproliferative disease in past 5 yr - Requirement for use of drugs that alter folate metabolism - History of alcohol abuse or unwillingness to limit consumption to < 4 drinks per week - Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed - Men who plan to father children during the study period or are unwilling to use contraception - Life expectancy < 3 years or unlikely to comply in judgment of investigator - Chronic use of oral or IV steroid therapy or other immunosuppressive or biologic response modifiers - History of hepatitis B or C - Chronic pericardial effusion, pleural effusion or ascites - New York Heart Association Class IV heart failure
16 Nov '12
The description was updated.
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While inflammation contributes crucially to atherothrombosis, it is unknown whether inhibition of inflammation per se will lower vascular event rates. The primary aim of the Cardiovascular Inflammation Reduction Trial (CIRT) is to directly test the inflammatory hypothesis of atherothrombosis by evaluating whether or not low-dose methotrexate (LDM) will reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable post-myocardial infarction patients with type 2 diabetes or metabolic syndrome, conditions associated with an enhanced pro-inflammatory response. CIRT is a randomized, double-blind, placebo-controlled, multi-center, event-driven trial that will randomize 7,000 men and women from the United States and Canada. Following a five- to six-week open-label run-in, eligible participants who have suffered documented myocardial infarction in the past five years will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM. The target methotrexate dose among those allocated to active therapy is 15 to 20 mg po per week, a dose within the range of that commonly used for the treatment of rheumatoid arthritis. All study participants will additionally receive 1.0 mg oral folate to be taken daily six days per week. LDM complications will be minimized through education programs for all investigators and coordinators, through enhanced communication with study participants, by limiting enrollment to those with no evidence of malignancy, hepatitis, renal dysfunction, chronic infection, pulmonary disease, or other risk factors for toxicity; by conducting an initial 5- to 6-week active-therapy run-in designed to eliminate individuals who are either intolerant of or unable to adhere to treatment before randomization; and through regular monitoring of liver function and hematologic indices using a centralized methodology designed to ensure participant safety, allow for dose adjustments while maintaining the study blind, and provide an efficient method to address issues of compliance and follow-up on a cost-effective centralized basis. The primary trial endpoint is the rate of recurrent myocardial infarction, stroke, or cardiovascular death. Secondary endpoints include all-cause mortality, incident diabetes among those with metabolic syndrome at study entry; hemoglobin A1c (HbA1c) control among those with diabetes at study entry; incident venous thrombosis; incident congestive heart failure, and incident atrial fibrillation. The trial is event driven such that in the absence of extreme effects, the trial will conclude after accrual of at least 530 primary endpoints, an effect estimated to provide 90 percent power to detect a 25 percent relative risk reduction. The potential clinical impact of CIRT is broad as it has sufficient power to directly address core issues in the inflammatory hypothesis of atherothrombosis, and thus, if successful, will open major new directions for cardiovascular treatment.
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None.
The eligibility criteria were updated.
New
Inclusion Criteria: - Documented myocardial infarction within the past five years AND - Type 2 diabetes AND/OR metabolic syndrome - Completed any planned coronary revascularization procedures - Medically stable for at least 60 days prior to screening - Age ≥ 18 years at screening Exclusion Criteria: - Chronic liver disease - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - Chronic infectious disease - Interstitial lung disease or pulmonary fibrosis - Myeloproliferative disease in past 5 years - HIV positive - Requirement for, or intolerance to, methotrexate or folate - History of non-basal cell malignancy or treatment for lymphoproliferative disease in past 5 yr - Requirement for use of drugs that alter folate metabolism - History of alcohol abuse or unwillingness to limit consumption to < 4 drinks per week - Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed - Men who plan to father children during the study period or are unwilling to use contraception - Life expectancy < 3 years or unlikely to comply in judgment of investigator - Chronic use of oral or IV steroid therapy or other immunosuppressive or biologic response modifiers - History of hepatitis B or C - Chronic pericardial effusion, pleural effusion or ascites - New York Heart Association Class IV heart failure
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Inclusion Criteria: - Documented myocardial infarction within the past five years AND - Type 2 diabetes OR metabolic syndrome - Completed any planned coronary revascularization procedures - Medically stable for at least 60 days prior to screening - Age ≥ 18 years at screening Exclusion Criteria: - Chronic liver disease - Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease - Chronic infectious disease - Chronic pulmonary disease, such as COPD/emphysema, interstitial lung disease or pulmonary fibrosis - Myeloproliferative disease in past 5 years - HIV positive - Requirement for, or intolerance to, methotrexate or folate - History of non-basal cell malignancy or treatment for lymphoproliferative disease in past 5 yr - Requirement for use of drugs that alter folate metabolism - History of alcohol abuse or unwillingness to limit consumption to ≤ 3 drinks per week - Woman of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed - Men who plan to father children during the study period or are unwilling to use barrier methods of contraception - Life expectancy < 3 years or unlikely to comply in judgment of investigator - Chronic use of oral or IV steroid therapy or other immunosuppressive or biologic response modifiers (see drug list in Manual of Operations) - History of hepatitis B or C - Chronic pericardial effusion, pleural effusion or ascites - New York Heart Association Class IV heart failure
27 Jun '12
The Summary of Purpose was updated.
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The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack. This trial is funded by the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH).
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The Cardiovascular Inflammation Reduction Trial (CIRT) is a randomized clinical trial investigating whether taking low-dose methotrexate reduces heart attacks, strokes, or death in people with type 2 diabetes or metabolic syndrome that have had a heart attack.
Trial was updated to "Phase 3."