Glycine Antagonist Fails to Improve Function in Ischemic Stroke Patients
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WESTPORT, CT (Reuters Health) Apr 04 - When given to patients after an acute ischemic stroke, gavestinel (GV150526), an antagonist of the glycine site of the NMDA receptor, does not improve functional outcome at 3 months, according to the results of a phase III trial, reported in today's issue of The Journal of the American Medical Association.
"Of course we were disappointed," Dr. Ralph L. Sacco, from Columbia University, New York, said in an interview with Reuters Health. "We felt that this drug had good promise in the test tube and in the animal models, it seemed safe in the phase II trials, but we had no idea of its efficacy until we did the phase III trial."
Dr. Sacco and colleagues, with the Glycine Antagonist in Neuroprotection (GAIN) Americas trial, randomized 1367 ischemic stroke patients in the US and Canada, median age 72 years, to gavestinel or placebo. Patients in the gavestinel group received an intravenous loading dose of 800-mg gavestinel up to 6 hours after stroke onset, plus five maintenance doses of 200 mg each, given every 12 hours over 3 days.
At 3 months, there was no benefit attributable to gavestinel in functional capacity as measured by the Barthel Index. The rate of functional independence was 39% among patients in the gavestinel group compared with 37% of those in the placebo group.
Gavestinel, a product of GlaxoSmithKline, Research Triangle Park, North Carolina, "joins the growing list of neuroprotectants that have not shown improved outcomes for patients with acute stroke, despite promising preclinical results," Dr. Sacco and colleagues note.
"About 6 months ago we knew that the results of the international trial of gavestinel were negative, so we figured that it was likely our trial would be negative, too," Dr. Sacco told Reuters Health. "We are still hopeful that other neuroprotectives will be developed and tested, and that this concept will prove to be clinically useful," he added.
Despite the failure of gavestinel, "increased understanding of the dynamic physiology and molecular aspects of penumbra, along with identification of its potential capacities for improvement by using prompt and novel diagnostic methods, may prove useful for developing new and much-needed approaches for neuroprotection therapy in acute stroke," Dr. Fred Plum from New York Presbyterian Hospital, writes in a journal editorial.
JAMA 2001;285:1719-1728,1760-1761. |
