Glyburide Advantage in Malignant Edema and Stroke Pilot "GAMES-PILOT"

Completed

Phase 1/2 Results

Update History

10 Jun '14
The Summary of Purpose was updated.
New
The study objective is to assess the feasibility of enrolling, evaluating, and treating with RP-1127 (Glyburide for Injection) severe anterior circulation ischemic stroke patients, whether or not treated with standard of care IV rtPA. Patients must be between 18-80 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 - 210 cm3, and time from symptom onset to start of study infusion must be ≤10 hr.
Old
The study objective is to assess the feasibility of enrolling, evaluating, and treating with RP-1127 (Glyburide for Injection) severe anterior circulation ischemic stroke patients, whether or not treated with standard of care IV rtPA. Patients must be between 18-60 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 - 210 cm3, and time from symptom onset to start of study infusion must be ≤10 hr.
21 Mar '12
A location was updated in Chicago.
New
The overall status was removed for Rush University Medical Center.
A location was updated in Baltimore.
New
The overall status was removed for University of Maryland Medical Center.
A location was updated in Boston.
New
The overall status was removed for Massachusetts General Hospital.
A location was updated in Pittsburgh.
New
The overall status was removed for University of Pittsburgh Medical Center.
6 Oct '11
The Summary of Purpose was updated.
New
The study objective is to assess the feasibility of enrolling, evaluating, and treating with RP-1127 (Glyburide for Injection) severe anterior circulation ischemic stroke patients, whether or not treated with standard of care IV rtPA. Patients must be between 18-60 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 - 210 cm3, and time from symptom onset to start of study infusion must be ≤10 hr.
Old
The study objective is to assess the feasibility of enrolling, evaluating, and treating with RP-1127 (Glyburide for Injection) severe anterior circulation ischemic stroke patients, whether or not treated with standard of care IV rtPA. Patients must be between 18-60 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 - 210 cm3, and time from symptom onset to start of study infusion must be ?10 hr.
The eligibility criteria were updated.
New
Inclusion Criteria: - A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory. - Pre-morbid mRS 0 - 1. - A baseline DWI lesion between 82 cm3 and 210 cm3 on MRI. - Patients treated with IV rtPA should meet established criteria for IV rtPA administration in the 0-3 and 3-4.5 hr time periods, respectively. - The time to the start of infusion of study compound must be ≤ 10 hr after time of symptom onset - Age ≥18 years and ≤70 years. - Provision of written informed consent by the patient or from a legally authorized representative according to institutional guidelines and national regulations. Exclusion Criteria: - Evidence from imaging or pre-enrollment investigation of any diagnosis other than acute ischemic stroke likely to cause the presenting symptoms and signs. - Commitment to decompressive craniectomy (DC) prior to enrollment, or follow-ing enrollment and prior to start of study compound. - Treatment with IA rtPA or by mechanical means for clot disruption or with hypo-thermia. - Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators. - Pre-morbid mRS ≥ 2. - Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ≥ 2 on item 1a on the NIHSS); loss of other brain stem reflexes attributable to herniation according to the investigator's judgment. - CT or MRI evidence of hemorrhage or anteroseptal/pineal shift greater ≥2 mm prior to enrollment. - Rapidly improving symptoms. - Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of < 30 mL/min/1.73 m2. - Severe liver disease or ALT, AST, or bilirubin >2 times normal. - Blood glucose <55 mg/dL at enrollment or immediately prior to administration of RP-1127, or a clinically significant history of hypoglycemia. - Diagnosis of decompensated heart failure (e.g. clinical diagnosis of pulmonary edema, chest x-ray consistent with heart failure, tachypnea > 20, etc.) - Sulfonylurea treatment within 30 days. - Known allergy to sulfa or specific allergy to sulfonylurea drugs. - Known G6PD enzyme deficiency. - Pregnancy or breast-feeding. Women must be either post-menopausal (judged by the investigator), permanently sterilized or, if of childbearing age, must have a negative test for pregnancy obtained before enrollment. - Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <3 months not related to current stroke, or those unlikely to be com-pliant with follow up. - Patients who, in the opinion of the investigator, are not suitable for the study (rea-son to be documented).
Old
Inclusion Criteria: - A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory. - Pre-morbid mRS 0 - 1. - A baseline DWI lesion between 82 cm3 and 210 cm3 on MRI. - Patients treated with IV rtPA should meet established criteria for IV rtPA administration in the 0-3 and 3-4.5 hr time periods, respectively. - The time to the start of infusion of study compound must be ? 10 hr after time of symptom onset - Age ?18 years and ?70 years. - Provision of written informed consent by the patient or from a legally authorized representative according to institutional guidelines and national regulations. Exclusion Criteria: - Evidence from imaging or pre-enrollment investigation of any diagnosis other than acute ischemic stroke likely to cause the presenting symptoms and signs. - Commitment to decompressive craniectomy (DC) prior to enrollment, or follow-ing enrollment and prior to start of study compound. - Treatment with IA rtPA or by mechanical means for clot disruption or with hypo-thermia. - Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators. - Pre-morbid mRS ? 2. - Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ? 2 on item 1a on the NIHSS); loss of other brain stem reflexes attributable to herniation according to the investigator's judgment. - CT or MRI evidence of hemorrhage or anteroseptal/pineal shift greater ?2 mm prior to enrollment. - Rapidly improving symptoms. - Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of < 30 mL/min/1.73 m2. - Severe liver disease or ALT, AST, or bilirubin >2 times normal. - Blood glucose <55 mg/dL at enrollment or immediately prior to administration of RP-1127, or a clinically significant history of hypoglycemia. - Diagnosis of decompensated heart failure (e.g. clinical diagnosis of pulmonary edema, chest x-ray consistent with heart failure, tachypnea > 20, etc.) - Sulfonylurea treatment within 30 days. - Known allergy to sulfa or specific allergy to sulfonylurea drugs. - Known G6PD enzyme deficiency. - Pregnancy or breast-feeding. Women must be either post-menopausal (judged by the investigator), permanently sterilized or, if of childbearing age, must have a negative test for pregnancy obtained before enrollment. - Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <3 months not related to current stroke, or those unlikely to be com-pliant with follow up. - Patients who, in the opinion of the investigator, are not suitable for the study (rea-son to be documented).