Observations from the RESET clinical trial: A post-hoc per protocol analysis of clinical outcomes with percutaneous 60-day medial branch PNS in chronic low back pain.

Background: Percutaneous 60-day peripheral nerve stimulation (PNS) of the lumbar medial branches is a minimally invasive treatment option for chronic low back pain (CLBP). A recent randomized controlled trial (RESET Clinical Trial) met its primary endpoint, with a significantly greater proportion of participants treated with 60-day PNS (n = 112) reporting ≥50% reductions in average low back pain compared to those treated with physician-directed usual care with standard interventional management (n = 110; e.g., ablations, injections, physical therapy) at 3 months post start of treatment. Objective: Building on the published findings from the Full Analysis Set, this post-hoc analysis primarily explored whether per protocol treatment delivery (bilateral stimulation that generated sensations covering the majority of the painful region in the low back for 6-12 h per day) was associated with response to 60-day PNS. Additional post-hoc evaluations explored the influence of clinical variables across the study population and investigated outcomes within exploratory subgroups of common clinical pain profiles (e.g. Methods: Univariate logistic regressions evaluated associations between variables (treatment delivery and clinical variables) and responder rate (≥50% reduction in average pain at 3 months). Results: The results suggest per protocol treatment delivery is associated with positive outcomes following treatment with 60-day PNS for CLBP (odds ratio = 3.04, 95% confidence interval = [1.16, 7.93], p = 0.023). Within this clinical trial's population as defined by the inclusion and exclusion criteria, neither clinical variables (e.g., age, pain duration, gender, average pain intensity, pain interference, and disability) nor response to a medial branch block had a significant impact on treatment response. Additional post-hoc analyses showed positive outcomes with 60-day PNS among exploratory cohorts defined by common facetogenic and discovertebral pain features. Reductions in pain extended to improvements in pain interference and disability, with benefits sustained at all completed timepoints through 6 months (follow-up beyond 6 months is ongoing). Conclusions: Together, these findings suggest that 60-day PNS treatment delivery is an important determinant of outcomes, underscoring the role of proper lead implantation, patient education, and treatment adherence in clinical practice. ClinicalTrials gov identifier: NCT04246281.