Author(s): Diener H.-C.; Goadsby P.J.; Hoffmann J.; Marin J.; Ashina M.; Al-Karagholi M.A.-M.; Sinclair A.; Mitsikostas D.; Magis D.; Pozo-Rosich P.; Sieira P.I.; Lainez M.J.; Gaul C.; Silver N.; Liebler E.; Ferrari M.D.
Source: Cephalalgia : An International Journal of Headache; Sep 2019
Publication Date: Sep 2019
Publication Type(s): Article
Abstract:INTRODUCTION: Non-invasive vagus nerve stimulation (nVNS; gammaCore) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. METHOD(S): This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6-8 hours apart). RESULT(S): Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n=165; baseline, 7.9 days) and 1.80 for sham (n=167; baseline, 8.1 days) (p=0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with>=67% adherence per month demonstrated significant differences between nVNS (n=138) and sham (n=140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p=0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common. CONCLUSION(S): Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The “sham” device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. Study identification and registration: PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844.