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Abstract
Objective: To assess the efficacy and safety of adding propranolol to topiramate in chronic migraine subjects inadequately controlled with topiramate alone.
Methods: This was a double-blind, placebo-controlled, randomized clinical trial conducted through the National Institute of Neurological Disorders and Stroke Clinical Research Collaboration, expected to randomize 250 chronic migraine subjects inadequately controlled (≥10 headaches/month) with topiramate (50–100 mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks 16 to 24) compared with baseline (weeks −4 to 0).
Results: A planned interim analysis was performed after 48 sites randomized 171 subjects. The data and safety monitoring board recommended ending the trial after determining that it would be highly unlikely for the combination to result in a significant reduction in 28-day headache rate compared with topiramate alone if all 250 subjects were randomized. No safety concerns were identified. At study closure, 191 subjects were randomized. The 6-month reduction in moderate to severe 28-day headache rate and total 28-day headache rate for combination therapy vs topiramate alone was not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91).
Conclusions: This study does not provide evidence that the addition of propranolol LA to topiramate adds benefit when chronic migraine is inadequately controlled with topiramate alone.
Classification of evidence: This study provides Class II evidence that propranolol LA, added to topiramate, is ineffective in chronic migraine patients who fail topiramate monotherapy.
GLOSSARY
- ANCOVA=
- analysis of covariance;
- BDI=
- Beck Depression Inventory;
- CM=
- chronic migraine;
- CMTT=
- Chronic Migraine Treatment Trial;
- DSMB=
- data and safety monitoring board;
- IRB=
- institutional review board;
- ITT=
- intent-to-treat;
- MIDAS=
- Migraine Disability Assessment;
- MSQL=
- Migraine Specific Quality of Life;
- OR=
- odds ratio
Footnotes
Study funding: Supported by NIH National Institute of Neurological Disorders and Stroke Contract HHSN265200523641C. Ortho-McNeil-Janssen Pharmaceuticals, Inc., donated the study-supplied topiramate used during the screening and randomization phases of this study.
Coinvestigators of the Chronic Migraine Treatment Trial Research Group are listed on the Neurology® Web site at www.neurology.org.
Editorial, page 940
Supplemental data at www.neurology.org
- Received March 29, 2011.
- Accepted September 7, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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