Frovatriptan for prophylactic treatment of cluster headache: lessons for future trial design.

Author(s): Pageler L, Katsarava Z, Lampl C, Straube A, Evers S, Diener HC, Limmroth V.

Affiliation(s): Department of Neurology, Cologne City Hospitals, Cologne, Germany.

Publication date & source: 2011, Headache. , 51(1):129-34

OBJECTIVE: The aim of this study was to determine whether frovatriptan would show efficacy in short term prophylactic treatment of episodic cluster headache (ECH) in comparison to placebo. BACKGROUND: The 5-hydroxytryptamine(1B/d) (5-HT(1B/d) )-agonists naratriptan, eletriptan, and frovatriptan have been shown to reduce the frequency of ECH. So far, no double-blind placebo-controlled trials have investigated the potential prophylactic effects of 5-HT(1B/d) -agonists in ECH. METHODS: The trial was conducted as a multi-center, placebo-controlled, randomized, double-blind, prospective phase III parallel-group trial with two independent treatment groups (5 mg frovatriptan vs placebo). It was planned to randomize about 96 patients (48 patients per group) into the trial to obtain 80 evaluable patients (40 patients per group). RESULTS: The study was prematurely discontinued after 13 months and enrollment of 11, instead of the planned 80 patients, by the sponsor due to infeasibility. Recruitment was slow and each of the patients included conducted major protocol violations. The differences in the primary and secondary endpoints were not significant. CONCLUSION: This study shows that particular therapeutic aims are impossible to be addressed in a double-blind, randomized, parallel group, study design with specific inclusion and exclusion criteria according to the International Headache Society (IHS) guidelines for controlled trials of drugs in cluster headache. Further studies are required to evaluate the potential efficacy of triptans in the prophylactic treatment of ECH. The outcome of the trial suggests that the recommendations of the Guidelines for controlled Trials of Drugs in Cluster Headache from the IHS should be revised.