Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial
Diener HC (1), Goadsby PJ (2), Ashina M (3), Al-Karagholi MA (3), Sinclair A (4), Mitsikostas D (5), Magis D (6), Pozo-Rosich P (7,8), Sieira PI (9), Làinez MJ (10), Gaul C (11), Silver N (12), Hoffmann J (2), Marin J (2), Liebler E (13), Ferrari MD (14); PREMIUM Study Group.
(1) Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
(2) NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK.
(3) Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark.
(4) Metabolic Neurology, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
(5) 1st Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.
(6) Neurology Department and Pain Clinic, CHR East Belgium, Liège, Belgium.
(7) Headache Unit, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
(8) Headache Research Group, Vall d'Hebron Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain.
(9) Clinica Universidad de Navarra, Pamplona, Spain.
(10) Catholic University of Valencia, University Clinic Hospital, Valencia, Spain.
(11) Migraine and Headache Clinic, Königstein, Germany.
(12) The Walton Centre, Liverpool, UK.
(13) electroCore, Inc., Basking Ridge, New Jersey, USA.
(14) Leiden University Medical Center, Leiden, The Netherlands.
Date: Sep 15, 2019Neurology [SP]
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.
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).
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.
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
CITATION Cephalalgia. 2019 Sep 15:333102419876920. doi: 10.1177/0333102419876920
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