title: Frovatriptan for prophylactic treatment of cluster headache: lessons for future trial design.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Cologne City Hospitals, Cologne, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Pageler
authors.forename: Zaza
authors.initials: Z
authors.lastname: Katsarava
authors.forename: Christian
authors.initials: C
authors.lastname: Lampl
authors.forename: Andreas
authors.initials: A
authors.lastname: Straube
authors.forename: Stefan
authors.initials: S
authors.lastname: Evers
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
mesh_terms: D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D003027:Cluster Headache / Q000517:prevention & control*; D004311:Double-Blind Method; D023381:Endpoint Determination; D017408:Guidelines as Topic; D006801:Humans; D018579:Patient Selection; D012107:Research Design; D018490:Serotonin Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014363:Tryptamines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D002227:Carbazoles; D018490:Serotonin Agents; D014363:Tryptamines; C108128:frovatriptan