(Stroke. 2000;31:1234.)
© 2000 American Heart Association, Inc.
Original Contributions |
Cervene (Nalmefene) in Acute Ischemic Stroke
Final Results of a Phase III Efficacy Study
From the Oregon Stroke Center (W.M.C.), Portland, Ore; Stanford Stroke Center (D.C.T.), Palo Alto, Calif; and Louisiana State University Medical Center (R.E.K.), Shreveport, La.
Correspondence to Wayne M. Clark, MD, Oregon Stroke Center, UHS 44, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. E-mail clarkw{at}ohsu.edu
Background and Purpose—The goals
of the present study were to assess the efficacy and safety of
nalmefene (Cervene) in patients with acute (
6 hours) ischemic
stroke and to investigate the safety of combined recombinant tissue
plasminogen activator and nalmefene in a
separate subset of patients. Nalmefene, an opioid
antagonist with relative 
receptor selectivity, has
shown neuroprotective effects in multiple experimental central nervous
system injury and ischemic models. Results from an earlier
phase II study in patients with acute ischemic stroke suggested
that nalmefene was safe and tolerable and may be effective for patients
<70 years old.
Methods—This investigation was a phase III, placebo-controlled,
double-blind, randomized study of a 24-hour infusion of nalmefene.
Patients with acute ischemic stroke who had an onset of
symptoms within 6 hours and a baseline score of 
4 on the NIH Stroke
Scale were randomized to receive either 60 mg nalmefene administered as
a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75
hours or placebo. The primary efficacy outcome was the proportion of
patients achieving a score of 60 on the Barthel Index and a rating of
"moderate disability" or better on the Glasgow Outcome Scale
at 12 weeks. Assessments were performed at baseline (predose), hours 12
and 24, days 2 and 7, and week 12.
Results—A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old.
Conclusions—Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours.
Key Words: narcotic antagonists • stroke • therapy
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