The long‐term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long‐term Effectiveness) trial

Summary Objective To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long‐term health‐related quality of life (HRQoL). Methods PuLsE (Open Prospective Randomized Long‐term Effectiveness) was a prospective, randomized, parallel‐group, open‐label, and long‐term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory‐89 total score; QOLIE‐89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES‐D), Neurological Disorders Depression Inventory‐Epilepsy scale (NDDI‐E), Clinical Global Impression‐Improvement scale (CGI‐I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow‐up QOLIE‐89 assessment (from months 3‐12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints. Results Significant between‐group differences in favor of VNS + BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI‐I score (respective p‐values