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

Authors

John Hatheway, Alexander Hersel, Jonathan Song, Mitchell Engle, Genaro Gutierrez, Vishal Khemlani, Leonardo Kapural, Gregory Moore, Reginald Ajakwe, Drew Trainor, Jennifer Hah, Peter S Staats, Paul Lynch, James Makous, Gary Heit, Shilpa Kottalgi, Mehul J Desai

Correspondence

Shilpa Kottalgi, Nalu Medical Inc, Carlsbad CA 92008, California, USA; skottalgi@nalumed.com

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.

Introduction

Peripheral nerve stimulation (PNS) is an established modality for the treatment of chronic peripheral neuralgia/neuropathy. The prevalence of neuropathic pain may be as high as 10% in the general population. When more conservative methods fail, then second-line therapies include nerve blocks and prescription medications. The last line of therapies involves PNS, which has been used as a treatment for chronic pain since the 1960s.

What is already known on this topic

• Peripheral nerve stimulation (PNS) has been widely used for over 50 years to treat intractable chronic pain of peripheral nerve origin.
• However, there is a paucity of data from randomised clinical trials.

What this study adds

• This study showed, through a well-controlled RCT using validated outcome instruments, that PNS therapy delivered by a micro-implantable pulse generator device significantly reduced pain and improved functional outcomes in over 80% of subjects treated.

Methods (continued)

The study design was intended to mimic real-world clinical practice as closely as possible. Consented subjects received baseline evaluations per protocol and standard clinical practice. Eligible subjects were then randomised into one of two arms: the active arm, which received PNS and CMM, and the control arm, which received CMM alone.

Subjects randomised to the control arm continued to receive CMM alone for the next 3 months. Upon completion of the 3-month primary endpoint, subjects in the control arm were given the option to crossover into the active arm.

Table 1

Subject demographics and baseline characteristics

Table 2

Patient reported outcomes (PRO) at 3 and 6-months

Results (continued)

The responder rate was 84% (36/43) at 3 months and 88% (37/42) at 6 months in the active arm compared with 3% (1/29) in the control arm. The PROs also demonstrated a statistically significant improvement in the active arm compared to the control.

Discussion

The study was a success by meeting the primary endpoint. The results of this RCT were significantly better than a separate PNS RCT with an older device. The improvements in the COMFORT study were similar to or better than the prospectively collected values reported in the PNS literature.

Conclusions (continued)

The study met the criterion for success—the active arm achieved statistical significance at the primary endpoint over the control arm in the responder rate. There was a strong safety profile with no serious adverse device effects and no reports of pocket pain. The outcomes were consistent with, and in some cases superior to, results in the PNS literature for the treatment of pain associated with chronic peripheral neuropathy or neuralgia. The small size of this micro-IPG allowed it to be used in all four of the anatomic locations studied without regard to body habitus.