Clinical study of a micro-implantable pulse generator for the treatment of peripheral neuropathic pain: 3-month and 6-month results from the COMFORT-randomised controlled trial

Abstract

Background: We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG).

Methods: Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle.

Results: At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable.

Conclusions: This study successfully reached its primary endpoint-the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available.

Keywords: CHRONIC PAIN; Neuralgia; Pain Management; Peripheral Nerve Injuries.

Figure 1. Subject disposition from consent to the 6-month endpoint. mITT, modified intention-to-treat.

Figure 2. Tornado plot. (A) Active arm at 3 months, (B) active arm at 6 months and (C) control arm at 3 months, showing per cent pain relief in each study subject. Responders were subjects with ≥50% pain reduction compared with their baseline NRS pain score. High responders were subjects with ≥80% pain reduction compared with their baseline pain score. NRS, numeric rating scale.

Figure 3. Mean NRS pain scores (BPI-Q5) and responder rates at 3 and 6 months. (A) Pain scores captured in the office at baseline and at 1 month, 3 months and 6 months for active and control arms. The mean per cent reduction in pain was statistically significant in the active arm compared with the control arm at 1, 3 and 6 months (p<0.001). Each data point represents mean±SEM. (B) Responder rates (≥50% improvement) and high responder rates (≥80% improvement) were statistically better in the active arm versus the control arm, at p<0.001 and p<0.05, respectively. Per cent pain reduction was also significantly better in the active arm versus the control arm at p<0.001. The sample size (N) is shown in parentheses. BPI-Q5, Brief Pain Inventory Question 5; NRS, numeric rating scale.

Figure 4. Peripheral nerve stimulation system used during the course of this study. The Nalu system consists of a micro-implantable pulse generator (<1.5 cc) that is powered by a therapy disc worn over the implant with an adhesive clip or a limb cuff. Bidirectional telemetry allows for optimal therapy delivery. There were three lead configurations employed during this study: four-contact leads with tines, four-contact leads without tines and eight-contact leads without tines. In addition, there were four micro-IPG configurations: Single port for four-contact leads, dual port for four-contact leads, single port for eight-contact leads and dual port for eight-contact leads.