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Sponsored by: |
National Institute of Neurological Disorders and Stroke (NINDS) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00039832 |
This study will evaluate the safety and effectiveness of two types of blood thinners, abciximab (ReoPro) and reteplase (Retavase) for restoring normal brain blood flow after ischemic stroke (stroke resulting from a blood clot in the brain).
The only therapy approved by the Food and Drug Administration to treat ischemic stroke is the clot buster drug rt-PA. This treatment, however, is effective only if begun within 3 hours of onset of the stroke and most patients do not get to the hospital early enough to benefit from it. There is thus a pressing need to develop effective stroke treatments that can be initiated more than 3 hours after onset.
Patients between 18 and 80 years of age who have experienced a mild or moderate acute stroke between 3 and 24 hours before starting study drugs may be eligible for this study. Candidates will be screened with a physical examination, blood tests and a magnetic resonance imaging (MRI) scan (if an MRI was not done during the stroke evaluation).
All participants will receive ReoPro. Some will also receive Retavase, which may boost the effectiveness of ReoPro. Retavase is administered in a single dose through a needle in the vein over 2 minutes. ReoPro is infused into the vein over 12 hours. Patients will be monitored with physical examinations, blood tests, computed tomography (CT) scans, and three or four MRI scans of the brain to evaluate both the response to treatment and side effects of the drugs. An MRI scan will be done 24 hours, 5 days and 30 days after starting the study medication, and possibly during screening for this study.
CT involves the use of specialized x-rays to obtain images of the brain. The patient lies still in the scanner for a short time while the X-ray images are formed. MRI uses a strong magnetic field and radio waves to demonstrate structural and chemical changes in tissue. MRI is more sensitive than x-ray in evaluating acute stroke. The patient lies on a table in a metal cylinder (the scanner) while the pictures are being taken. During part of the MRI, a medicine called gadolinium contrast is injected in a vein. This medicine brightens the images, creating better pictures of the blood flow.
Condition | Intervention | Phase |
---|---|---|
Cerebrovascular Accident |
Drug: Abciximab and Reteplase |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | ReoPro Retavase Reperfusion of Stroke Safety Study - Imaging Evaluation |
Estimated Enrollment: | 72 |
Study Start Date: | March 2002 |
Study Completion Date: | May 2008 |
Primary Completion Date: | May 2008 (Final data collection date for primary outcome measure) |
Objectives: This is a clinical trial to determine an acceptable dose of reteplase in combination with a fixed dose of abciximab for ischemic stroke 3-24 hours from onset.
Study Population: Patients will be selected by criteria to minimize likelihood of toxicity and maximize likelihood of response. These criteria include age 18-80 years old, acute ischemic stroke of moderate severity (NIH Stroke Scale less than or equal to 16 and lesion volume on diffusion MRI less than approximately one third of the volume of the middle cerebral artery territory), positive MRI evidence of hypoperfusion corresponding to the acute stroke symptoms, no MRI evidence of chronic micro-hemorrhages, and no other clinical, radiological or laboratory features associated with risk of hemorrhage with thrombolytic therapy.
Design: The study is open-label, dose escalation, safety and proof of principle study of the combination of intravenous abciximab and reteplase. A fixed dose of abciximab will be used in all patients: 0.25 mg/kg bolus (to a maximum of 30 mg) followed by a 0.125 microgram/kg/minute infusion (to a maximum of 10.0 microgram/minute) for 12 hours. The five dosing groups for the reteplase dose are 0 U, 2.5 U, 5.0 U, 7.5 U, and 10.0 U. A maximum of 72 patients will be treated using an adaptive statistical design, in which data on both the response and toxicity will be used to determine the dose for subsequent patients, thereby minimizing exposure to either ineffective or toxic doses. Non-investigational patient management will be standardized across all patients according to the NIH Stroke Center Clinical Care Pathway.
Outcome Measures: The primary efficacy endpoint for response will be reperfusion by MRI 24 hours after start of therapy. The primary safety endpoint for determination of toxicity will be any one of the following: symptomatic intracranial hemorrhage (ICH), major systemic hemorrhage, or other serious adverse event related to study drug administration, including death, within 48 hours from start of therapy. The maximum acceptable rate of toxicity will be 10% of patients treated at any dose level and the minimum acceptable rate of response will be 50% of patients treated at any dose level. The outcomes will be monitored by a Data and Safety Monitoring Committee, which will have the authority to stop or recommend modifications of the trial for safety concerns. Other clinical outcome variables and imaging variables will be recorded and analyzed in secondary and exploratory analyses. If an acceptable dose is identified, then that will be investigated in a subsequent randomized placebo-controlled trial.
Ages Eligible for Study: | 18 Years to 80 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Patients may be enrolled in the study only if they meet all of the following criteria:
Diagnosis of acute ischemic stroke with onset between 3 and 24 hours prior to planned start of study drugs.
Acute ischemic stroke is defined as a measurable neurological deficit of sudden onset, presumed secondary to focal cerebral ischemia, and not otherwise attributable to ICH or another disease process. Stroke onset will be defined as the time the patient was last known to be without the new clinical deficit. Patients whose deficits have worsened in the last 24 hours are not eligible if their first symptoms started more than 24 hours before.
If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be intact. A careful history is important to determine when the patient was last without the presenting deficits.
EXCLUSION CRITERIA:
Patients will be excluded from the study for any of the following reasons:
General:
Patients who would refuse blood transfusions if medically indicated.
Stroke Related:
Baseline NIHSS greater than 16.
MRI/CT Related:
Satellite DWI hyperintensity with corresponding hyperintensity on T2 weighted image or FLAIR in a vascular territory different than the index stroke (this is evidence of a new ischemic lesion possibly greater than 24 hours in duration).
Safety Related:
Congenital or acquired coagulopathy (e.g. secondary to anticoagulants causing either of the following:
Potentially Interfering with Outcome Assessment:
Serum creatinine, AST or ALT greater than 3 times the upper limit of normal for the local laboratory.
Drug Related:
United States, District of Columbia | |
Washington Hospital Center | |
Washington, District of Columbia, United States, 20010 | |
United States, Maryland | |
Suburban Hospital | |
Bethesda, Maryland, United States, 20814 | |
Washington Adventist Hospital | |
Takoma Park, Maryland, United States | |
Germany | |
Ruprecht Karl Heidelberg Hospital | |
Heidelberg, Germany |
Responsible Party: | National Institutes of Health ( Steven J. Warach, M.D./National Institute of Neurological Disorders and Stroke ) |
Study ID Numbers: | 020154, 02-N-0154 |
Study First Received: | June 12, 2002 |
Last Updated: | August 24, 2009 |
ClinicalTrials.gov Identifier: | NCT00039832 History of Changes |
Health Authority: | United States: Federal Government |
Stroke Abciximab Reteplase MRI Cerebral Blood Flow |
Anticoagulants Cerebral Infarction Stroke Vascular Diseases Central Nervous System Diseases Abciximab Fibrinolytic Agents Cardiovascular Agents Ischemia |
Brain Diseases Cerebrovascular Disorders Fibrin Modulating Agents Reteplase Brain Ischemia Platelet Aggregation Inhibitors Brain Infarction Infarction |
Anticoagulants Molecular Mechanisms of Pharmacological Action Cerebral Infarction Hematologic Agents Stroke Nervous System Diseases Vascular Diseases Central Nervous System Diseases Abciximab Fibrinolytic Agents Cardiovascular Agents |
Brain Diseases Cerebrovascular Disorders Pharmacologic Actions Fibrin Modulating Agents Therapeutic Uses Reteplase Brain Ischemia Platelet Aggregation Inhibitors Cardiovascular Diseases Brain Infarction |