ReoPro and Retavase to Treat Acute Stroke
Condition: Cerebrovascular Accident
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will determine the dose of Retavase that can safely be combined with ReoPro in
      treating acute ischemic stroke (stroke resulting from a blood clot in the brain). ReoPro and
      Retavase are currently approved by the Food and Drug Administration to treat heart problems
      caused by blockage of heart arteries. The only therapy approved by the Food and Drug
      Administration to treat ischemic stroke is the clot buster drug rt-PA. This treatment is
      effective only if begun within 3 hours of onset of the stroke, however, and most patients do
      not get to the hospital early enough to benefit from it.

      Patients between 18 and 80 years of age who have had 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 medical history and physical examination, blood tests, rating of neurological
      deficits such as cognition deficits or problems walking that resulted from the stroke, and a
      computed tomography (CT) scan of the head. CT involves the use of specialized X-rays to
      obtain images of the brain. The patient lies on a table that is moved into a cylindrical
      machine (the scanner) for the imaging study, which usually takes about 5 to 10 minutes.

      All participants will receive 0.25 mg/kg of ReoPro (maximum dose of 30 mg). The drug is
      infused into the vein over 12 hours. Some patients will also receive one of four doses of
      Retavase, which may boost the effectiveness of ReoPro in opening the blocked blood vessel.
      Retavase is given through a needle in the vein over 2 minutes. Patients will be monitored
      daily until discharge from the hospital, or until day 5, whichever is earlier. Assessments
      will include physical examinations, blood tests to examine factors involved in blood
      clotting, and CT scans to evaluate both the response to treatment and drug side effects. They
      will return for a follow-up examination and CT scan 30 days after treatment.

      ...
    

Detailed description: 
      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 criteria to minimize likelihood of toxicity
      and maximize likelihood of response. These criteria include age 18-80 years old, patients who
      cannot get acute MRI because of contraindication to or unavailability of MRI, acute ischemic
      stroke of moderate severity (NIH Stroke Scale less than or equal to 16 and ischemic changes
      on CT scan less than approximately one third of the volume of the middle cerebral artery
      territory), no evidence of hemorrhage on CT, and no other clinical, radiological or
      laboratory features associated with increased 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 0U, 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. Non-investigation 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 clinical improvement
      (complete recovery or improvement of 4 points or more on the NIH Stroke Scale) at 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 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.
    

Intervention name(s): Reopro; Retrovase
Intervention type(s): Drug; Drug
Intervention MeSH terms: Abciximab
Primary purpose: Treatment
Keywords: Stroke; Abciximab; Retavase; MRI; Cerebral Blood Flow