NCT00039832

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2002

Longer than P75 for phase_2

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2002

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 12, 2002

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 13, 2002

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2007

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2008

Completed
Last Updated

September 21, 2011

Status Verified

September 1, 2011

Enrollment Period

5.1 years

First QC Date

June 12, 2002

Last Update Submit

September 19, 2011

Conditions

Cerebrovascular Accident

Keywords

StrokeAbciximabReteplaseMRICerebral Blood Flow

Outcome Measures

Primary Outcomes (1)

  • Occurrence of symptomatic ICH, major systemic hemorrhage, or other serious adverse event, including death, within 48 hrs from start of study drug.

    30 days

Secondary Outcomes (1)

  • All ICH types (fatal, symptomatic, asymptomatic), all bleeding (major, minor, insignificant), deaths, all serious adverse events (by subtype) at the 48 hours, 5 days, and 30 days tabulated by dose group and overall.

Study Arms (2)

1

EXPERIMENTAL

CT

Drug: Abciximab (ReoPro) and Reteplase (Retavase)

2

EXPERIMENTAL

MRI

Drug: Abciximab (ReoPro) and Reteplase (Retavase)

Interventions

Abciximab (ReoPro) and Reteplase (Retavase)DRUG
12

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 to 16.
  • Evidence on PWI MRI of a perfusion defect corresponding to the acute stroke syndrome of at least 2cm in diameter in both long and short axis in any slice. The PWI will be assessed by relative mean transit time (MTT) images. The MRI evaluation must involve echo planar diffusion weighted imaging, MRA, and MRI perfusion. A normal appearing MRA with an appropriate perfusion defect is eligible. An apparent stenosis or occlusion on MRA with normal appearing perfusion distally will not be eligible. Poor quality or uninterpretable MRA will not make patient ineligible. Patients who have a normal DWI are eligible.
  • Age 18 - 80 years, inclusive.

You may not qualify if:

  • 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 impossible to determine with high degree of confidence.
  • Symptoms suggestive of subarachnoid hemorrhage, even if CT or MRI 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 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
  • Contraindication to MRI scan.
  • 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:
  • +37 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

Washington Adventist Hospital

Takoma Park, Maryland, United States

Location

Ruprecht Karl Heidelberg Hospital

Heidelberg, Germany

Location

Related Publications (3)

  • National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.

    PMID: 7477192BACKGROUND

  • Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999 Dec 1;282(21):2003-11. doi: 10.1001/jama.282.21.2003.

    PMID: 10591382BACKGROUND

  • Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 Oct 17;352(9136):1245-51. doi: 10.1016/s0140-6736(98)08020-9.

    PMID: 9788453BACKGROUND

Related Links

MeSH Terms

Conditions

Stroke

Interventions

Abciximabreteplase

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fab FragmentsImmunoglobulin FragmentsPeptide FragmentsPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 2
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

June 12, 2002

First Posted

June 13, 2002

Study Start

March 1, 2002

Primary Completion

April 1, 2007

Study Completion

May 1, 2008

Last Updated

September 21, 2011

Record last verified: 2011-09

Locations

US(3)DE(1)