Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.

Background: Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH.
Methods: PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n=48) with standard of care (SoC) alone (control (n=49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety
tolerability were also assessed.
Results: During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n=45) had a significantly greater reduction in the number of attacks per week vs controls (n=48) (-5.9 vs -2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p=0.02). Higher #50% response rates were
also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p<0.001). No serious treatment-related adverse events occurred.
Conclusion: Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC.