Comparative study of the efficacy of limaprost and pregabalin as single agents and in combination for the treatment of lumbar spinal stenosis: A prospective, double-blind, randomized controlled non-inferiority trial

Background Context Although the simultaneous management of neuronal ischemia-related pain and compression-demyelination-related neuropathic pain is considered optimal in treating lumbar spinal stenosis (LSS), the effect of combination therapy with pregabalin and limaprost has not been elucidated. Purpose This study aimed to compare the effects of limaprost and pregabalin individually and in combination for the treatment of LSS. Study Design This is a prospective, double-blind, double-dummy, randomized controlled trial. Patient Sample The sample consists of patients with LSS. Outcome Measures The baseline-adjusted Oswestry Disability Index (ODI) score, visual analog scale (VAS) scores for leg pain, the European Quality of Life-5 dimensions (EQ-5D), and initial claudication distance (ICD). Methods The present study (ClinicalTrials.gov, number NCT01888536) was a prospective, double-blind, double-dummy, randomized controlled trial designed to determine the efficacy of limaprost in alleviating leg pain, improving disability, and increasing walking distance in persons with degenerative LSS in three different treatment groups: limaprost alone, pregabalin alone, and combined limaprost and pregabalin through 1:1:1 allocation. The primary outcome was the baseline-adjusted ODI score at 8 weeks after treatment. The non-inferior margin of the ODI was set at δ=10 points. Results The baseline-adjusted ODI score (primary outcome) at 8 weeks after treatment in the limaprost group was not inferior to those in the pregabalin and limaprost+pregabalin groups. The overall changes of the baseline-adjusted ODI scores, VAS scores for leg pain, the EQ-5D, and ICD during the follow-up assessments over an 8-week period (secondary end point) were not different among the three groups. The baseline-adjusted ODI scores and VAS scores for leg pain decreasedsignificantly over time after treatment in all three groups. The baseline-adjusted EQ-5D score and ICD also increased significantly over time after treatment in all three groups. Conclusions The efficacy of limaprost for lumbar spinal stenosis was not inferior compared with that of pregabalin or the combination of limaprost and pregabalin in terms of disability. Therefore, combined treatment with limaprost and pregabalin does not provide additional relief in symptoms in patients with LSS compared with monotherapy with limaprost or pregabalin.