Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double‐blind, placebo‐controlled comparison.

Abstract

Eur Neurol. 2002;47(2):99‐107The 5‐HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40‐ and 80‐mg doses of eletriptan and 2 tablets of Cafergot were compared in a double‐blind, randomised, placebo‐controlled, parallel‐group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4‐point scale (3 = severe pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more eletriptan‐treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot‐treated patients (33%; p < 0.001) reported headache response (improvement from moderate‐to‐severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p < or = 0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated.Comment: As with all comparative trials with eletriptan, this comparative trial raises the important issue of blinding. Was the Cafergot encapsulated (hence potentially hindering the early phase of absorbtion)? This approach has been a major issue with previous eletriptan studies and may potentially make the results from this trial difficult to interpret. DSM One key issue in ensuring methodologically rigorous comparative trials is symmetry of comparative groups. I have come to believe that the controversy over encapsulation for blinding is neither about the pharmacokinetics of encapsulation, nor about the effectiveness of eletriptan, but rather about the methodology of comparison, which requires as much symmetry as possible. As Gawel and Wiebe wrote in a superb article explaining how to critically evaluate a comparison trial, “When faced with a potential confounder … readers need to estimate in which direction the results would be biased” in any comparative trial (Gawel M, Wiebe S. Evidence‐based analysis of a migraine treatment drug comparison trial. Cephalalgia. 2000;20[suppl 2]:33‐38). SJT