Cervene (nalmefene) in acute ischemic stroke - Final results of a phase III efficacy study

Background and Purpose-The goals of the present study were to assess the ef ficacy and safety of nalmefene (Cervene) in patients with acute (less than or equal to 6 hours) ischemic stroke and to investigate the safety of combi ned recombinant tissue plasminogen activator and nalmefene in a separate su bset of patients. Nalmefene. an opioid antagonist with relative kappa recep tor 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 nalme fene was safe and tolerable and may be effective for patients (<70 years ol d. Methods-This investigation was a phase III, placebo-controlled, double-blin d, 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 greater than or equal to 4 on the NIH Stroke Scale were randomize d to receive either 60 mg nalmefene administercd as a ID-mg bolus over 15 m inutes and then a 50-mg infusion over 23.75 hours or placebo, The primary e fficacy outcome was the proportion of patients achieving a score of greater than or equal to 60 on the Bathel Index and a rating of "moderate disabili ty" or better on the Glasgow Outcome Scale at 12 weeks. Assessments were pe rformed at baseline iprcdose), 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 d rug. Nalmefene was well tolerated. Overall, there was no significant differ ence in 3-month functional outcome for nalmefene treatment compared with pl acebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old, Conclusions-Although nalmeferne appears to be safe and well tolerated. this study failed to find any treatment benefit in stroke patients treated with in 6 hours.