title: Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study.
abstract: To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component.
  
  
  
  Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses).
  
  
  
  For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [-1.820, -0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005).
  
  
  
  The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component.
authors.affiliation: Division of Neurological Pain Research and Therapy, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.affiliation: Department of Anaesthesiology and Intensive Medicine, Interdisciplinary Center of Pain Therapy and Palliative Medicine, General Hospital Klagenfurt, Klagenfurt, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Likar
authors.affiliation: Rheumatology, Hospital Universitario La Paz, Idipaz, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Martin-Mola
authors.affiliation: Servicío de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.affiliation: Grünenthal Innovations - Global Biometrics, Grünenthal GmbH, Aachen, Germany.
authors.forename: Lieven
authors.initials: L
authors.lastname: Kennes
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Falke
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Steigerwald
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy*; D010098:Oxycodone / Q000008:administration & dosage* / Q000627:therapeutic use*; D010147:Pain Measurement; D010636:Phenols / Q000008:administration & dosage* / Q000627:therapeutic use*; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D010636:Phenols; D009270:Naloxone; D010098:Oxycodone; D000077432:Tapentadol
keywords: RCT; chronic low back pain; effectiveness; neuropathic pain; randomized controlled trial; tapentadol prolonged release