Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial

• Published in: Cephalalgia Vol. 42; no. 7; pp. 560 - 569
• Main Authors: Najib, Umer, Smith, Timothy, Hindiyeh, Nada, Saper, Joel, Nye, Barbara, Ashina, Sait, McClure, Candace K, Marmura, Michael J, Chase, Serena, Liebler, Eric, Lipton, Richard B
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2022
• Subjects: clinical trial; migraine prophylaxis; Neuromodulation; preventive therapy; nonpharmacologic treatment
• ISSN: 0333-1024; 1468-2982; 1468-2982
• DOI: 10.1177/03331024211068813

Aim Evaluate the efficacy and safety of non-invasive vagus nerve stimulation for migraine prevention. Methods After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period. Results Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespecified modified intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was ∼60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, −0.83; p = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p = 0.0481). Prespecified subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported. Conclusions These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability profile of this therapy. Trial Registration: ClinicalTrials.gov (NCT03716505).