title: 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.
abstract: 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.
  
  
  
  This study aimed to compare the effects of limaprost and pregabalin individually and in combination for the treatment of LSS.
  
  
  
  This is a prospective, double-blind, double-dummy, randomized controlled trial.
  
  
  
  The sample consists of patients with LSS.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Spine Center and Department of Orthopaedic Surgery, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 166 Gumiro, Bundang-gu, Sungnam 463-707, South Korea.
authors.forename: Ho-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Inje University Sanggye Paik Hospital, 1342, Dongil-ro, Nowon-gu, Seoul, South Korea.
authors.forename: Jin Hyok
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Guri Hospital, Hanyang University College of Medicine, 153, Gyeongchun-ro, Guri-si, Gyeonggi-do, South Korea.
authors.forename: Ye Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, 134 Shinchondong, Seodaemunku, Seoul, South Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Suk
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University College of Medicine and SMG-SNU Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, South Korea.
authors.forename: Jae Hyup
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Medical College of Hallym University, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, South Korea.
authors.forename: Moon Soo
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, 134 Shinchondong, Seodaemunku, Seoul, South Korea. Electronic address: shmoon@yuhs.ac.
authors.forename: Seong-Hwan
authors.initials: SH
authors.lastname: Moon
mesh_terms: D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008161:Lumbosacral Region / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011788:Quality of Life; D013130:Spinal Stenosis / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D000527:Alprostadil; C059238:limaprost
keywords: Combined treatment; European Quality of Life 5 dimension (EQ-5D); Initial claudication distance; Limaprost; Lumbar spinal stenosis; Non-inferiority trial, randomized controlled trial; Oswestry disability index; Pregabalin; Visual analog scale