Cervene in acute ischemic stroke: Results of a double-blind, placebo-controlled, dose-comparison study

Cervene (nalmefene), an opioid antagonist with relative kappa receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. The agent already has a well-established safety profile in various clinical indications. Results from an earlier pilot study in 44 acute stroke patients suggest that Cervene administered by 24-hour maintenance infusion was safe and tolerable. The primary and secondary objectives of the current study were to assess the dose-related safety and preliminary efficacy of Cervene in patients with acute ischemic stroke.The present investigation was a Phase II, placebo-controlled, double-blind, randomized, dose-comparison, parallel-group study of a 24-hour administration of Cervene injection. Patients with acute ischemic stroke, onset of symptoms within 6 hours, and baseline score > or =4 on the National Institute of Health Stroke Scale (NIHSS) were randomized to 1 of 4 treatment groups: Cervene 6 mg, 20 mg, 60 mg or placebo. The primary efficacy outcome was the proportion of patients achieving a score of > or =60 on the Barthel Index and a rating of "moderate disability" or better on the Glasgow Outcome Scale at 12 weeks.A total of 312 patients were randomized at 28 centers. All doses of Cervene were well tolerated. Overall, there was no significant difference in 3-month functional outcome for any dose of Cervene treatment compared with placebo. However, a prospective secondary analysis showed that both male and female patients less than age 70 years may have had an improved 3-month outcome.The results of this study indicate that the competitive kappa receptor opiate antagonist Cervene can be given safely to acute stroke patients at doses up to 60 mg/24 hr. Although overall there was no significant difference in the 3-month outcome, Cervene treatment may be associated with improved outcomes for patients younger than age 70.