Introduction

Refractory mechanical chronic low back pain (CLBP) is often linked to impaired neuromuscular control and reduced quality of the multifidus muscles, which provide stability to the lumbar spine. Consequently, analgesic treatments often lack long-term effectiveness. Prior studies have suggested efficacy of an implantable neurostimulator which elicits repetitive multifidus contractions aimed at restoring neuromuscular control. We evaluated this device in an international, multicenter, randomized, active sham-controlled, double-blinded trial with single-arm crossover. (clinicaltrials.gov/show/NCT02577354)

Methods/Materials

Eligible patients were implanted and randomly assigned to receive therapeutic or subthreshold stimulation (sham-control) for 30 minutes, twice daily. The primary endpoint compared responder rates at 120 days, with a ‘Responder’ having ≥30% average VAS reduction without any increase in pain medication. Patients in the sham-control group crossed over to therapeutic stimulation at 120 days.

Results

At baseline (N=204), CLBP-duration was 14±11 years, age 47±9 years, VAS 7.3±0.7 cm and ODI 39±10.

At 120days (N=204), the primary endpoint did not reach significance (57% vs. 47%). The primary cumulative proportion of responder analysis, secondary and supporting analyses consistently favored treatment over sham (p<0.05). A prespecified modified intention-to-treat analysis which excluded patients who increased pain medications for reasons unrelated to low back pain, also demonstrated significance in favor of the therapy (p<0.05) as did the first four out of the five secondary endpoints. Blinding was assessed and considered effective. At one year, improvements in the combined treatment and crossover group (N=160) were clinically meaningful. 65% of patients had ≥50% VAS improvement, 53% had VAS ≤2.5 cm, 59% had ≥20 points ODI improvement and 49% (30/61) eliminated or reduced opioids. The safety profile compared favorably to published neurostimulation experiences.

Discussion

This was the first randomized, sham-controlled trial of a neurostimulation system for the restorative treatment of CLBP and the size of the sham response was thus far unknown. Although effects of this rehabilitative treatment accrue over time, endpoint timing was set to 120 days for ethical and pragmatic considerations. Interpretation of the composite primary endpoint is confounded by dichotomization and analgesic intake for reasons other than LBP. Indeed, both the cumulative proportion of responder analysis as well as the modified intention-to-treat analysis in this study return statistically significant results.

Conclusions

While the primary efficacy endpoint, a comparison of responder rates, did not reach statistical significance at 120 days, the primary, secondary, supporting and long-term outcome analyses suggest safety, effectiveness and durability of restorative neurostimulation in patients with refractory mechanical CLBP.