Transcutaneous vagus nerve stimulation as add-on therapy versus pharmacotherapy alone (TRAVAST): study protocol for a prospective, randomised, triple-blind, controlled, multicentre trial

Introduction Despite optimised antiseizure medication, pharmacoresistant epilepsy still affects a substantial proportion of adult patients, especially when epilepsy surgery is not possible or is rejected. Transcutaneous vagus nerve stimulation (t-VNS) is a non-invasive neuromodulatory approach for which the evidence from randomised studies to date does not allow for a reliable assessment of its benefits due to small case numbers and methodological limitations. Transcutaneous vagus nerve stimulation as add-on therapy versus pharmacotherapy alone (TRAVAST) is a prospective, multicentre, randomised, triple-blind, controlled trial to investigate whether t-VNS as an add-on to established pharmacotherapy improves seizure-related and patient-relevant outcomes in adults with pharmacoresistant epilepsy. Methods and analysis A total of 164 adults (aged 18–65) with pharmacoresistant epilepsy and clinically manifest seizures who are not eligible for or refuse (further) resective epilepsy surgery will be enrolled at 15 sites. Patients are assigned 1:1 to active t-VNS or sham stimulation in addition to stable antiseizure medication for 12 months. t-VNS is performed using a non-implanted stimulator with an ear electrode as a daily self-administered therapy in the home environment. The primary outcome is the proportion of patients with at least 50% reduction in mean seizure frequency after 52±2 weeks compared with a 4-week baseline period, documented in a standardised epilepsy diary. Secondary outcomes include additional response rates, seizure freedom, seizure severity, health-related quality of life, psychological and cognitive parameters, treatment retention and safety, including device-related events and sudden unexpected death in epilepsy. Ethics and dissemination The trial protocol has been approved by an ethics committee (Ethics Committee of LMU of Munich). All patients will provide written consent prior to inclusion and can withdraw from the trial at any time without this affecting their further care. The results will be published in specialist journals, reported in trial registries, made available anonymously for scientific use and communicated back to the participating physicians, patients and the public. Trial registration number DRKS00039592.