POSITIVE Stroke Clinical Trial

Active, not recruiting

Phase N/A Results N/A

Update History

4 Oct '17
The Summary of Purpose was updated.
New
Primary Endpoint: The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, with appropriate image selection, treated with mechanical thrombectomy within 6-12 hours of symptom onset have less stroke related disability and improved good functional outcomes as compared to those treated with best MT with respect to endpoint defined as: • 90-day global disability assessed via the modified Rankin score (mRS), analyzed using raw mRS scores. Statistical details can be found in section 7.2. Secondary Endpoints: - 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS - Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days - Mortality at 30 and 90 days - Intracranial hemorrhage with neurological deterioration (NIHSS worsening >4) within 24 hours of randomization - Procedure related serious adverse events (SAE's) - Arterial revascularization measured by TICI 2b or 3 following device use
Old
Primary Endpoint: The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, with appropriate image selection, treated with mechanical thrombectomy within 6-12 hours of symptom onset have less stroke related disability and improved good functional outcomes as compared to those treated with best MT with respect to endpoint defined as: • 90-day global disability assessed via the modified Rankin score (mRS), analyzed using raw mRS scores. Statistical details can be found in section 7.2. Secondary Endpoints: - 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS - Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days - Mortality at 30 and 90 days - Intracranial hemorrhage with neurological deterioration (NIHSS worsening >4) within 24 hours of randomization - Procedure related serious adverse events (SAE's) - Arterial revascularization measured by TICI 2b or 3 following device use
The description was updated.
New
Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has shown potential benefit out to 4.5 hours. Mechanical thrombectomy for AIS patients has been shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression of thrombectomy devices over the last several years has resulted in faster recanalization times while maintaining a high degree of safety. This has resulted in improved patient outcomes, similar to prior randomized trial data showing improved outcomes over medical therapy or earlier devices. Data from the MERCI trial suggests that patients > 85 as well as those with a baseline NIHSS score > 30 are unlikely to benefit from thrombectomy. Patients with rapidly improving neurologic deficits likely will have an excellent recovery with conventional care, precluding the ability to detect a beneficial treatment effect of thrombectomy. Pilot data incorporating physiologic imaging has shown that appropriate patients can be selected for thrombectomy. This selection methodology has shown the ability to maintain the same level of safety and efficacy as those patients treated in the highly selective environment of a clinical trial, despite presenting far beyond accepted time based standards. Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population, particularly since no data currently is available addressing the comparability of imaging penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be reproducible at multiple centers and with different imaging modalities. However, all prospective interventional stroke studies performed to date have been restricted by the 8-hour time window.
Old
Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has shown potential benefit out to 4.5 hours. Mechanical thrombectomy for AIS patients has been shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression of thrombectomy devices over the last several years has resulted in faster recanalization times while maintaining a high degree of safety. This has resulted in improved patient outcomes, similar to prior randomized trial data showing improved outcomes over medical therapy or earlier devices. Data from the MERCI trial suggests that patients > 85 as well as those with a baseline NIHSS score > 30 are unlikely to benefit from thrombectomy. Patients with rapidly improving neurologic deficits likely will have an excellent recovery with conventional care, precluding the ability to detect a beneficial treatment effect of thrombectomy. Pilot data incorporating physiologic imaging has shown that appropriate patients can be selected for thrombectomy. This selection methodology has shown the ability to maintain the same level of safety and efficacy as those patients treated in the highly selective environment of a clinical trial, despite presenting far beyond accepted time based standards. Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population, particularly since no data currently is available addressing the comparability of imaging penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be reproducible at multiple centers and with different imaging modalities. However, all prospective interventional stroke studies performed to date have been restricted by the 8-hour time window.
The gender criteria for eligibility was updated to "All."
The eligibility criteria were updated.
New
Inclusion Criteria: 1. Age 18 and older (i.e., candidates must have had their 18th birthday) 2. NIHSS ≥8 at the time of neuroimaging 3. Presenting or persistent symptoms within 6-12 hours of when groin puncture can be obtained 4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1 bifurcation) 5. The operator feels that the stroke can be appropriately treated with traditional endovascular techniques (endovascular mechanical thrombectomy without adjunctive devices such as stents) 6. Pts are within 6-12 hours of symptom onset, that have received IV-tPA without improvement in symptoms are eligible for this study. Patients presenting earlier than 6 hours should be treated according to local standard of care. 7. Pre-event Modified Rankin Scale score 0-1 8. Consenting requirements met according to local IRB Exclusion Criteria: 1. Patient is less than 6-hours from symptom onset 2. Rapidly improving neurologic examination 3. Absence of large vessel occlusion on non-invasive imaging 4. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory 5. Absence of an associated large penumbra as defined by physiologic imaging according to standard of practice at the participating institution 6. Any intracranial hemorrhage in the last 90 days 7. Known irreversible bleeding disorder 8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 2.5 or institutionally equivalent prothrombin time of 2.5 times normal 9. Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction 10. Inability to tolerate, clinically documented evidence in medical history of adverse reaction to, or contraindication to medications used in treatment of the stroke 11. Contraindication to CT and MRI (i.e., iodine contrast allergy or other condition that prohibits imaging from either CT or MRI) 12. Known allergy to contrast used in angiography that cannot be medically controlled 13. Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL) 14. Women who are currently pregnant or breast-feeding (Women of child-bearing potential must have a negative pregnancy test prior to the study procedure (either serum or urine) 15. Evidence of active infection (indicated by fever at or over 99.9 °F and/or open draining wound) at the time of randomization 16. Current use of cocaine or other vasoactive substance 17. Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 90 days 18. Patients who lack the necessary mental capacity to participate or are unwilling or unable to comply with the protocol's follow up appointment schedule (based on the investigator's judgment) Head CT or MRI Scan Exclusion Criteria - Presence of blood on imaging (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.) - High density lesion consistent with hemorrhage of any degree - Significant mass effect with midline shift - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan or ASPECTS of < 7; Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment
Old
Inclusion Criteria: 1. Age 18 and older (i.e., candidates must have had their 18th birthday) 2. NIHSS ≥8 at the time of neuroimaging 3. Presenting or persistent symptoms within 6-12 hours of when groin puncture can be obtained 4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1 bifurcation) 5. The operator feels that the stroke can be appropriately treated with traditional endovascular techniques (endovascular mechanical thrombectomy without adjunctive devices such as stents) 6. Pts are within 6-12 hours of symptom onset, that have received IV-tPA without improvement in symptoms are eligible for this study. Patients presenting earlier than 6 hours should be treated according to local standard of care. 7. Pre-event Modified Rankin Scale score 0-1 8. Consenting requirements met according to local IRB Exclusion Criteria: 1. Patient is less than 6-hours from symptom onset 2. Rapidly improving neurologic examination 3. Absence of large vessel occlusion on non-invasive imaging 4. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory 5. Absence of an associated large penumbra as defined by physiologic imaging according to standard of practice at the participating institution 6. Any intracranial hemorrhage in the last 90 days 7. Known irreversible bleeding disorder 8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 2.5 or institutionally equivalent prothrombin time of 2.5 times normal 9. Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction 10. Inability to tolerate, clinically documented evidence in medical history of adverse reaction to, or contraindication to medications used in treatment of the stroke 11. Contraindication to CT and MRI (i.e., iodine contrast allergy or other condition that prohibits imaging from either CT or MRI) 12. Known allergy to contrast used in angiography that cannot be medically controlled 13. Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL) 14. Women who are currently pregnant or breast-feeding (Women of child-bearing potential must have a negative pregnancy test prior to the study procedure (either serum or urine) 15. Evidence of active infection (indicated by fever at or over 99.9 °F and/or open draining wound) at the time of randomization 16. Current use of cocaine or other vasoactive substance 17. Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 90 days 18. Patients who lack the necessary mental capacity to participate or are unwilling or unable to comply with the protocol's follow up appointment schedule (based on the investigator's judgment) Head CT or MRI Scan Exclusion Criteria - Presence of blood on imaging (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.) - High density lesion consistent with hemorrhage of any degree - Significant mass effect with midline shift - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan or ASPECTS of < 7; Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment
A location was updated in Jacksonville.
New
The overall status was removed for Baptist Health.
A location was updated in Worcester.
New
The overall status was removed for Univesity of Massachusetts-Worcester.
A location was updated in Trenton.
New
The overall status was removed for Captial Health.
A location was updated in Albany.
New
The overall status was removed for Albany Medical Center.
A location was updated in Buffalo.
New
The overall status was removed for University of Buffalo Neurosurgery.
A location was updated in Stony Brook.
New
The overall status was removed for Stony Brook Medical Center.
A location was updated in Cleveland.
New
The overall status was removed for Cleveland Clinic.
A location was updated in Columbus.
New
The overall status was removed for Ohio Health.
A location was updated in Charleston.
New
The overall status was removed for Medical University of South Carolina.
A location was updated in Chattanooga.
New
The overall status was removed for Tennessee Interventional Associates.
A location was updated in Memphis.
New
The overall status was removed for Methodist Healthcare - Memphis.
A location was updated in Nashville.
New
The overall status was removed for Vanderbilt University.
A location was updated in Morgantown.
New
The overall status was removed for West Virginia University.
A location was updated in Madison.
New
The overall status was removed for Wisconsin University.
3 Oct '15
The Summary of Purpose was updated.
New
Primary Endpoint: The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, with appropriate image selection, treated with mechanical thrombectomy within 6-12 hours of symptom onset have less stroke related disability and improved good functional outcomes as compared to those treated with best MT with respect to endpoint defined as: • 90-day global disability assessed via the modified Rankin score (mRS), analyzed using raw mRS scores. Statistical details can be found in section 7.2. Secondary Endpoints: - 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS - Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days - Mortality at 30 and 90 days - Intracranial hemorrhage with neurological deterioration (NIHSS worsening >4) within 24 hours of randomization - Procedure related serious adverse events (SAE's) - Arterial revascularization measured by TICI 2b or 3 following device use
Old
The primary objective of this randomized trial is to determine the safety and efficacy of intra-arterial reperfusion in Acute Ischemic Stroke (AIS) patients ineligible for IV-tPA as selected by physiologic imaging criteria.
The description was updated.
New
Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has shown potential benefit out to 4.5 hours. Mechanical thrombectomy for AIS patients has been shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression of thrombectomy devices over the last several years has resulted in faster recanalization times while maintaining a high degree of safety. This has resulted in improved patient outcomes, similar to prior randomized trial data showing improved outcomes over medical therapy or earlier devices. Data from the MERCI trial suggests that patients > 85 as well as those with a baseline NIHSS score > 30 are unlikely to benefit from thrombectomy. Patients with rapidly improving neurologic deficits likely will have an excellent recovery with conventional care, precluding the ability to detect a beneficial treatment effect of thrombectomy. Pilot data incorporating physiologic imaging has shown that appropriate patients can be selected for thrombectomy. This selection methodology has shown the ability to maintain the same level of safety and efficacy as those patients treated in the highly selective environment of a clinical trial, despite presenting far beyond accepted time based standards. Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population, particularly since no data currently is available addressing the comparability of imaging penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be reproducible at multiple centers and with different imaging modalities. However, all prospective interventional stroke studies performed to date have been restricted by the 8-hour time window.
Old
Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has shown potential benefit out to 4.5 hours. IAT for AIS patients has been shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression of IAT devices over the last several years has resulted in faster recanalization times while maintaining a high degree of safety. This has resulted in improved patient outcomes, similar to prior randomized trial data showing improved outcomes over medical therapy or earlier devices. Data from the MERCI trial suggests that patients > 85 as well as those with a baseline NIHSS score > 30 are unlikely to benefit from embolectomy. Patients with rapidly improving neurologic deficits likely will have an excellent recovery with conventional care, precluding the ability to detect a beneficial treatment effect of embolectomy. Pilot data incorporating physiologic imaging has shown that appropriate patients can be selected for IAT. This selection methodology has shown the ability to maintain the same level of safety and efficacy as those patients treated in the highly selective environment of a clinical trial, despite presenting far beyond accepted time based standards. Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population, particularly since no data currently is available addressing the comparability of imaging penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be reproducible at multiple centers and with different imaging modalities. However, all prospective interventional stroke studies performed to date have been restricted by the 8 hour time window. Currently there are no active studies assessing the safety and efficacy of IAT for patients presenting outside of the IV-tPA selection window when selected by physiologic imaging. The primary aim of acute ischemic stroke treatment is restoring a patient that is severely neurologically impaired due to a blockage of a major brain blood vessel back to their previous functional status. Identification and selection of appropriate patients is always paramount to good clinical outcomes. Evidence supports the safety of IAT for patients presenting with AIS within 8 hours. Pilot data support IAT in some patients after 8 hours based on selection using physiological perfusion imaging. The purpose of this randomized trial is to demonstrate the safety and efficacy of mechanical thrombectomy over medical therapy (MT) for treating acute ischemic stroke patients ineligible for IV-tPA with persistent symptoms within a 12 hour time window from symptom onset as selected by physiologic perfusion imaging criteria.
The eligibility criteria were updated.
New
Inclusion Criteria: 1. Age 18 and older (i.e., candidates must have had their 18th birthday) 2. NIHSS ≥8 at the time of neuroimaging 3. Presenting or persistent symptoms within 6-12 hours of when groin puncture can be obtained 4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1 bifurcation) 5. The operator feels that the stroke can be appropriately treated with traditional endovascular techniques (endovascular mechanical thrombectomy without adjunctive devices such as stents) 6. Pts are within 6-12 hours of symptom onset, that have received IV-tPA without improvement in symptoms are eligible for this study. Patients presenting earlier than 6 hours should be treated according to local standard of care. 7. Pre-event Modified Rankin Scale score 0-1 8. Consenting requirements met according to local IRB Exclusion Criteria: 1. Patient is less than 6-hours from symptom onset 2. Rapidly improving neurologic examination 3. Absence of large vessel occlusion on non-invasive imaging 4. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory 5. Absence of an associated large penumbra as defined by physiologic imaging according to standard of practice at the participating institution 6. Any intracranial hemorrhage in the last 90 days 7. Known irreversible bleeding disorder 8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 2.5 or institutionally equivalent prothrombin time of 2.5 times normal 9. Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction 10. Inability to tolerate, clinically documented evidence in medical history of adverse reaction to, or contraindication to medications used in treatment of the stroke 11. Contraindication to CT and MRI (i.e., iodine contrast allergy or other condition that prohibits imaging from either CT or MRI) 12. Known allergy to contrast used in angiography that cannot be medically controlled 13. Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL) 14. Women who are currently pregnant or breast-feeding (Women of child-bearing potential must have a negative pregnancy test prior to the study procedure (either serum or urine) 15. Evidence of active infection (indicated by fever at or over 99.9 °F and/or open draining wound) at the time of randomization 16. Current use of cocaine or other vasoactive substance 17. Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 90 days 18. Patients who lack the necessary mental capacity to participate or are unwilling or unable to comply with the protocol's follow up appointment schedule (based on the investigator's judgment) Head CT or MRI Scan Exclusion Criteria - Presence of blood on imaging (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.) - High density lesion consistent with hemorrhage of any degree - Significant mass effect with midline shift - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan or ASPECTS of < 7; Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment
Old
Inclusion Criteria: 1. Age 18 to 80 years (i.e., candidates must have had their 18th birthday, but not had their 81st birthday). 2. NIHSS ≥8 at the time of neuroimaging 3. Presenting or persistent symptoms within 12 hours of when groin puncture can be obtained 4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1 bifurcation). 5. The operator feels that the stroke can be appropriately treated with traditional endovascular techniques (endovascular thrombectomy without adjunctive devices such as stents). 6. Pre-event Modified Rankin Scale score 0-1 7. Consenting requirements met according to local IRB Exclusion Criteria: 1. Pt eligible for IV-tPA therapy. 2. Rapidly improving neurologic examination. 3. Absence of large vessel occlusion on non-invasive imaging. 4. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory 5. Absence of an associated large penumbra as defined by physiologic imaging according to standard of practice at the participating institution 6. Subarachnoid hemorrhage in the past 60 days 7. Any intracranial hemorrhage in the last 90 days 8. Known irreversible bleeding disorder 9. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with INR > 2.5 or institutionally equivalent prothrombin time of 2.5 times normal. 10. Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction 11. Inability to tolerate, clinically documented evidence in medical history of adverse reaction or contraindication to medications used in treatment of the stroke 12. Contraindication to CT and MRI (ie. Iodine contrast allergy, or other condition that prohibits imaging from either CT or MRI) 13. Known allergy to contrast used in angiography that cannot be medically controlled 14. Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL) 15. Pregnancy, breast-feeding, or positive pregnancy test [either serum or urine] (Woman of child-bearing potential must have a negative pregnancy test prior to the study procedure.) 16. Evidence of active infection [indicated by fever (at or over 99.9 °F) and/or open draining wound] at the time of randomization 17. Current use of cocaine or other vasoactive substance 18. Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 90 days. 19. Based on investigator's judgment, patient does not have the necessary mental capacity to participate or is unwilling or unable to comply with protocol follow up appointment schedule. 20. Currently participating in another interventional (drug, device, etc) research project Head CT or MRI Scan Exclusion Criteria - Presence of blood on imaging (SAH, ICH, etc). - High density lesion consistent with hemorrhage of any degree. - Significant mass effect with midline shift. - Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan or ASPECTS of < 7. Sulcal effacement and / or loss of grey-white differentiation alone are not contraindications for treatment.
18 Oct '13
A location was updated in Charleston.
New
The overall status was removed for Medical University of South Carolina.