Topiramate versus propranolol for prevention of chronic migraine: A randomized double-blind controlled trial (TOP-PRO study)

ABSTRACT

Background and aims: Except for topiramate, oral preventive treatment for chronic migraine (CM) lacks credible evidence. We conducted TOP-PRO-study, a double-blind RCT, to know whether propranolol is as efficacious (non-inferior) and safe as topiramate for the prevention of CM. Methods: CM patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Safety was also assessed. Results: COVID-19 pandemic and lockdown halted the recruitment before the trial reached the planned sample size of 244. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. At baseline, mean (± SD) migraine days were 17.3 ± 6.7 vs 17.6 ± 6.6 days for patients in the topiramate and propranolol group respectively. The mean migraine days change was −5.29 ± 1.17 vs −7.28 ± 1.14 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of −1.99 with a CI of −5.23 to 1.25 days). There was no significant difference in the incidence of adverse events between the two groups. Conclusions: Our study found that propranolol was non-inferior, non-superior to topiramate, and equally safe for the preventive treatment of CM. (Academic study Clinical Trials Registry-India CTRI/2019/05/018997).