Abciximab in Wake-up Stroke
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||Does Abciximab Save Hypoperfused Ischemic Brain Tissue in Wake-Up Stroke: A Placebo-Controlled, Randomized, MR Imaging Study|
- To investigate whether abciximab compared with placebo is able to save brain tissue as assessed by MRI performed prior to inclusion in the study and 5-7 days after stroke onset:
- (PWI1 - FLAIR2) / PWI1 (“brain salvage index”: area at risk not progressed into final infarct size)and (FLAIR2 - DWI1) / DWI1 (relative growth of infarct size from admission to days 5-7).
- To compare abciximab and placebo with regard to the:
- Proportion of mRS responders at 90 ± 14 days (mRS responder is defined as: mRS at 90 ± 14 days = 0 if baseline NIHSS score was 4-7, mRS at 90 ± 14 days <1 if baseline NIHSS score was 8-14, and mRS at 90 ± 14 days <2 if baseline NIHSS score was 15),
- Functional outcome (as measured by the mRS and NIHSS, and all cause mortality at 90 ± 14 days),
- Incidence of fatal ICH, non-fatal symptomatic parenchymal hemorrhage, or other symptomatic ICH through discharge/day 5,
- Proportion of subjects with non-intracranial bleeding through discharge/day 5,
- Ratio (DWI2-DWI1)/DWI1 for detecting new infarcts.
|Study Start Date:||March 2005|
|Study Completion Date:||May 2005|
Intravenous (IV) administration of recombinant tissue plasminogen activator (rt-PA) is the only approved therapy in patients with acute ischemic stroke presenting within 3 hours of symptom onset. Approximately 17-30% of ischemic strokes are found on awakening. Since stroke onset cannot be determined for patients who awake with stroke, they are de facto ineligible for thrombolytic therapy. Nevertheless, it is possible that some patients suffered their stroke within a few hours prior to become awake, and may thus be good candidates for thrombolysis. Combined diffusion- (DWI) and perfusion- (PWI) weighted MR imaging (MRI) is able to identify hypoperfused but still viable brain tissue, the potentially salvageable ischemic penumbra (PWI-DWI mismatch). A recent study has examined 34 patients with wake-up stroke and a median National Institute of Health Stroke Scale (NIHSS) score of 13 (range 6 to 22) with DWI and PWI. The authors found that 73% of patients presenting with non-lacunar stroke within 3 hours of waking from sleep had a PWI-DWI mismatch with larger hypoperfused areas. This imaging pattern may be associated with potential benefit from thrombolysis beyond the current 3-hour window. Induced or spontaneous reperfusion of brain areas with initial PWI hypoperfusion has been associated with reduced infarction and a favourable clinical outcome. A phase IIa placebo-controlled safety and pilot efficacy trial of abciximab in patients with acute ischemic stroke treated within 24 hours from symptoms onset found that abciximab caused no symptomatic intracranial hemorrhage and showed a trend toward a higher rate of patients with minimal residual disability1. Thus, abciximab may be an attractive therapy option in patients with wake-up stroke and a PWI-DWI mismatch.
The purpose of the prospective, randomized, double blind, placebo-controlled multicenter pilot study is to evaluate the effectiveness of abciximab on rescuing the hypoperfused brain tissue, as assessed by MRI, and the relative safety of abciximab in patients with wake-up stroke.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00167765
|Heinrich Heine University|
|University of Zurich, Department of Neurology|
|Zurich, Switzerland, 8091|
|Principal Investigator:||Ralf W. Baumgartner, MD||University of Zurich|
|Principal Investigator:||Mario Siebler, MD||Heinrich Heine University Dusseldorf|