title: Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design.
abstract: In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.
authors.affiliation: Service de Neurologie, CHU de Rangueil, Toulouse, France. geraud.g@chu-toulouse.fr
authors.forename: G
authors.initials: G
authors.lastname: Geraud
authors.forename: J
authors.initials: J
authors.lastname: Olesen
authors.forename: V
authors.initials: V
authors.lastname: Pfaffenrath
authors.forename: P
authors.initials: P
authors.lastname: Tfelt-Hansen
authors.forename: R
authors.initials: R
authors.lastname: Zupping
authors.forename: H C
authors.initials: HC
authors.lastname: Diener
authors.forename: R
authors.initials: R
authors.lastname: Sweet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D010080:Oxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D023303:Oxazolidinones; D012008:Recurrence; D012107:Research Design; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D018170:Sumatriptan / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014363:Tryptamines
chemical_list: D010080:Oxazoles; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan; D018170:Sumatriptan