Randomised trial on episodic cluster headache with an angiotensin II receptor blocker

Objectives: The aim of this study was to evaluate the angiotensin II receptor antagonist candesartan as prophylactic medication in patients with episodic cluster headache. Methods: This study comprised a prospective, placebo-controlled, double-blind, parallel-designed trial performed in seven centres in Scandinavia. Forty (40) patients with episodic cluster headache (ICHD-2) were recruited and randomised over a five-year period to placebo or 16 mg candesartan in the first week, and placebo or 32 mg candesartan in the second and third week. Results: The number of cluster headache attacks (primary efficacy variable) during the three-week treatment period was reduced from 14.3±9.2 attacks in week 1 to 5.6±7.0 attacks in week 3 (±61%) in the candesartan group and from 16.8±14.1 attacks in week 1 to 10.5±11.3 attacks in week 3 (±38%) in the placebo group. The difference between the candesartan and placebo group was not significant with the pre-planned non-parametric ranking test, but a post-hoc exact Poisson test, which takes into account the temporal properties of the data, revealed a significant result (p<0.0001). Conclusions: This was a negative trial. Post-hoc statistics suitable to describe the temporal changes in cluster headache indicate that conduction of future larger studies may be justified.