ReActiv8-B Trial 2-Year Data Publication in Neuromodulation
Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward.
This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery.
Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation.
At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake.
At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction.
The study is registered on clinicaltrials.gov with identifier NCT02577354.
- Chronic low back pain
- durability
- functional segmental stability
- multifidus muscle
- restorative neurostimulation
Most cases of acute low back pain resolve spontaneously without treatment, but for chronic low back pain (CLBP), the prognosis is not favorable.1 Patients with CLBP often endure impaired quality of life, depression, anxiety, and sleep disturbance.2,3 Most CLBP patients suffer from mechanical/musculoskeletal pain that is predominantly nociceptive in nature and have no indication for spine surgery.4, 5, 6, 7
The multifidus muscles are the most important stabilizers of the lumbar spine and play a crucial role in providing segmental stability in response to changes in posture and protection against sudden perturbations.8, 9, 10 Mechanical CLBP is often associated with impaired neuromuscular control and degeneration of the lumbar multifidus muscles.9,11, 12, 13 Persistent back pain–induced inhibition and disruption of proprioceptive signaling have also been linked to long-term motor cortex reorganization.14 Results of motor control exercise programs specifically targeting the multifidus muscle are mixed.15,16 The isolated muscle contractions required to reverse impaired neuromuscular control are difficult to achieve voluntarily, especially in the presence of underlying inhibition and degeneration of the multifidus muscle.17,18 To overcome these limitations to rehabilitation, a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was developed to electrically stimulate the medial branch of the L2 dorsal ramus nerve to elicit isolated multifidus muscle activation.19,20
A recent double-blind, randomized, sham-controlled pivotal trial provided safety and effectiveness evidence for premarket approval from the United States Food and Drug Administration (FDA) in 2020.21
The objective of the prospective, observational analyses reported here was to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery.
Materials and MethodsData for this secondary analysis were obtained from the cohort of 204 patients enrolled at 26 multidisciplinary centers in the United States, Australia, and Europe in the randomized, sham-controlled, double-blind pivotal trial. All patients were receiving therapeutic stimulation from four months onward. Details regarding patient eligibility, study design, implant procedure, and medium-term results through one year have been previously published.21
PatientsStudy participants were adults with a diagnosis of disabling mechanical CLBP (ie, a seven-day recall of average LBP of ≥6.0 and ≤9.0 cm on the 10-cm visual analog scale [VAS] and Oswestry disability index [ODI] of ≥21 and ≤60 points on a scale from 0 to 100). Mechanical CLBP was defined as low back pain without significant radicular symptoms. Participants had low back pain on at least half of the days in the previous year, were nonresponsive to a minimum of 90 days of nonsurgical medical management including medication and physical therapy, and had a positive prone instability test result (provocative pain test using posterior-anterior pressure on individual lumbar vertebrae that improves with activation of the posterior lumbar musculature) consistent with impaired neuromuscular control of the multifidus muscle and consequent lumbar segmental instability.22 Full eligibility criteria are provided in the Supplementary Data.
Trial Design and OversightThe conduct of the trial complied with the FDA regulations, ISO 14155, International Conference on Harmonization, and the Declaration of Helsinki. Local institutional review board or ethics committee approval was obtained at each site, and all participants provided written informed consent. Results are reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.23 The study is registered on clinicaltrials.gov with identifier NCT02577354.
Dr. Chris Gilligan and the team of ReActiv8-B investigators have been pivotal to establishing the emerging field of “Restorative Neurostimulation” for refractory chronic mechanical low back pain. In this publication, the researchers detail the randomized, sham-controlled, double-blinded ReActiv8-B trial to demonstrate safety and efficacy of a novel, implantable restorative-neurostimulator targeting functional instability of the lumbar spine in patients with refractory mechanical chronic low back pain. These 2-year patient outcome demonstrate long-term efficacy of ReActiv8 Restorative Neurostimulation.