ReoPro and Retavase to Treat Acute Stroke

Launched by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) · Sep 25, 2002

Keywords

ClinConnect Summary

Objectives: This is the companion protocol to the ROSIE protocol. This clinical trial will determine an acceptable dose of reteplase in combination with a fixed dose of abciximab for ischemic stroke 3-24 hours from onset in patients screened with brain CT rather than MRI (as required by the ROSIE protocol). The importance of this study relative to ROSIE will be its relevance to the large proportion of acute stroke patients who cannot have a screening MRI, because of contraindications or unavailability of emergency MRI at their hospital.

Study Population: Patients will be selected by criter...

Gender

ALL

Eligibility criteria

• • INCLUSION CRITERIA
• 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.
• • Disabling neurological deficit attributable to the acute stroke at the start of study drugs.
• • NIHSS less than or equal to16
• • Age 18 - 80 years, inclusive.
• • Patients not evaluable for the ROSIE protocol because of MRI contraindication or MRI unavailability or technically inadequate diffusion and perfusion MRI.
• • EXCLUSION CRITERIA
• Patients will be excluded from the study for any of the following reasons:
• • General
• • Current participation in another study with an investigational drug or device within, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final assessment in this trial.
• • Time interval since stroke onset of less than 24 hours is impossible to determine with high degree of confidence.
• • Symptoms suggestive of subarachnoid hemorrhage, even if CT scan is negative for hemorrhage.
• • Evidence of acute myocardial infarction defined as having at least two of the following three features: 1) Chest pain suggestive of cardiac ischemia 2) EKG findings of ST elevation of more greater than 0.2 mV in 2 contiguous leads, new onset left bundle branch block, ST segment depression, or T-wave inversion 3) Elevated troponin I
• • Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
• • Patients who would refuse blood transfusions if medically indicated
• • Stroke Related
• • Neurological deficit that has led to stupor or coma (NIHSS level of consciousness score greater than or equal to 2).
• • High clinical suspicion of septic embolus.
• • Minor stroke with non-disabling deficit or rapidly improving neurological symptoms.
• • Baseline NIHSS greater than 16.
• • MRI/CT Related
• • Evidence of acute or chronic ICH by head CT.
• • CT evidence of non-vascular cause for the neurological symptoms.
• • Signs of mass effect causing shift of midline structures.
• • Patient excluded from the ROSIE protocol by MRI findings.
• • Acute ischemic changes on CT larger than approximately one third of the territory of the middle cerebral artery territory by qualitative assessment.
• • Safety Related
• • Persistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greater than 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control.
• • Anticipated need for major surgery within 72 hours after start of study drugs, e.g., carotid endarterectomy, hip fracture repair.
• • Any intracranial surgery, serious head trauma (any head injury that required hospitalization), or stroke within the past 3 months.
• • Stroke within the past 3 months.
• • History of ICH at any time in the past.
• • Major trauma at the time of stroke, e.g., hip fracture.
• • Blood glucose greater than 200 mg/dl.
• • Presence or history of intracranial neoplasm or arteriovenous malformation.
• • Intracranial aneurysm, unless surgically treated greater than 3 months.
• • Major hemorrhage in past 21 days.
• • Major surgery, serious trauma, lumbar puncture, arterial puncture at a non-compressible site, or biopsy of a parenchymal organ in last 14 days. Major surgical procedures include but are not limited to the following: major thoracic or abdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy or other vascular surgery, and organ transplant. For non-listed procedures, the operating surgeon should be consulted to assess the risk.
• • Presumed or documented history of vasculitis.
• • Known systemic bleeding disorder, e.g., von Willebrand's disease, hemophilia, others.
• • Platelet count less than 100,000 cells/mL.
• Congenital or acquired coagulopathy (e.g., secondary to anticoagulants) causing either of the following:
• • 1. Activated partial thromboplastin time (aPTT) prolongation greater than 2 seconds above the upper limit of normal for local laboratory, except if due to isolated factor XII deficiency. Protamine sulfate reversal of heparin effect does not alleviate this criterion.
• • 2. INR greater than or equal to 1.4. Patients receiving warfarin prior to entry are eligible provided INR is less than 1.4 and warfarin can be safely discontinued for at least 48 hours.
• • Potentially Interfering with Outcome Assessment
• • Life expectancy less than 3 months.
• • Other serious illness, e.g., severe hepatic, cardiac, or renal failure; acute myocardial infarction; or a complex disease that may confound treatment assessment.
• • Serum creatinine, AST or ALT greater than 3 times the upper limit of normal for the local laboratory.
• • Drug Related
• • Treatment of the qualifying stroke with any thrombolytic or GPIIbIIIa inhibitor outside of this protocol.
• • Any administration of a thrombolytic drug in the prior 7 days.
• • Treatment of the qualifying stroke with intravenous heparin unless aPTT prolongation is no greater than 2 seconds above the upper limit of normal for local laboratory prior to study drug initiation.
• • Treatment of the qualifying stroke with a low molecular weight heparinoid.
• • Previous administration of abciximab, if known.
• • Known allergy to murine proteins.
• • Anticoagulation caused by herbal therapy.