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The STAT Study: A Randomized Controlled Trial

David G. Sherman, MD; Richard P. Atkinson, MD; Thomas Chippendale, MD; Kenneth A. Levin, MD; Ken Ng, MD; Nancy Futrell, MD; Chung Y. Hsu, MD; David E. Levy, MD; for the STAT Participants

JAMA. 2000;283:2395-2403.

Context  Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator, but bleeding complications, including intracranial hemorrhage, are a recognized complication.

Objective  To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke.

Design  The Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group, double-blind, placebo-controlled trial conducted between August 1993 and January 1998.

Setting  Forty-eight centers, primarily community hospitals, in the United States and Canada.

Patients  A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis.

Interventions  Patients were randomly assigned to receive ancrod (n=248) or placebo (n=252) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset, followed by infusions lasting approximately 1 hour at 96 and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen levels to 1.18 to 2.03 µmol/L.

Main Outcome Measures  The primary efficacy end point was functional status, with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value, compared by treatment group. Primary safety variables included symptomatic intracranial hemorrhage and mortality.

Results  Favorable functional status was achieved by more patients in the ancrod group (42.2%) than in the placebo group (34.4%; P=.04) by the prespecified covariate-adjusted analysis. Mortality was not different between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for the placebo group; P=.62), and the proportion of severely disabled patients was less in the ancrod group than in the placebo group (11.8% vs 19.8%; P=.01). The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age, stroke severity, sex, prestroke disability, and time to treatment (3 or >3 hours after stroke onset). There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P=.01).

Conclusion  In this study, ancrod had a favorable benefit-risk profile for patients with acute ischemic stroke.

Author Affiliations: Division of Neurology, University of Texas Health Science Center, San Antonio (Dr Sherman); Mercy General Hospital, Sacramento, Calif (Dr Atkinson); Tri-City Medical Center, Oceanside, Calif (Dr Chippendale); the Valley Hospital, Ridgewood, NJ (Dr Levin); Munroe Regional Medical Center, Ocala, Fla (Dr Ng); Intermountain Stroke Center, Salt Lake City, Utah (Dr Futrell); Washington University School of Medicine, St Louis, Mo (Dr Hsu); and Knoll Pharmaceutical Co, Mount Olive, NJ (Dr Levy).

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