title: Efficacy of paracetamol, diclofenac and advice for acute low back pain in general practice: design of a randomized controlled trial (PACE Plus).
abstract: Low back pain is common and associated with a considerable burden to patients and society. There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain. This trial will assess the effectiveness of paracetamol, diclofenac and placebo for acute low back pain over a period of 4 weeks. Furthermore, this trial will assess the additional effectiveness of paracetamol, diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks.
  
  
  
  The PACE Plus trial is a multi-center, placebo-blinded, superiority randomized controlled trial in primary care, with a follow-up of 12 weeks. Patients with acute low back pain aged 18-60 years presenting in general practice will be included. Patients are randomized into four groups: 1) Advice only (usual care conforming with the clinical guideline of the Dutch College of General Practitioners); 2) Advice and paracetamol; 3) Advice and diclofenac; 4) Advice and placebo. The primary outcome is low back pain intensity measured with a numerical rating scale (0-10). Secondary outcomes include compliance to treatment, disability, perceived recovery, costs, adverse reactions, satisfaction, sleep quality, co-interventions and adequacy of blinding. Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models. An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life. Explorative analyses will be performed to assess effect modification by predefined variables. Ethical approval has been granted. Trial results will be released to an appropriate peer-viewed journal.
  
  
  
  This paper presents the design of the PACE Plus trial: a multi-center, placebo-blinded, superiority randomized controlled trial in primary care that will assess the effectiveness of advice only, paracetamol, diclofenac and placebo for acute low back pain.
  
  
  
  Dutch Trial Registration NTR6089 , registered September 14th, 2016.
  
  
  
  Version 4, June 2016.
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center, PO box 2040, 3000 CA, Rotterdam, The Netherlands. m.schreijenberg@erasmusmc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Schreijenberg
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center, PO box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: P A J
authors.initials: PA
authors.lastname: Luijsterburg
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center, PO box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Y D M
authors.initials: YD
authors.lastname: Van Trier
authors.affiliation: Department of Biostatistics, Erasmus MC, University Medical Center, PO box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Rizopoulos
authors.affiliation: Department of Health Policy and Management/iMTA, Erasmus University Rotterdam, PO Box 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Koopmanschap
authors.affiliation: Dutch Association for Back pain Patients 'The Spine', Bentinckstraat 21, Lichtenvoorde, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Voogt
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Sydney, NSW, 2050, Australia.
authors.forename: C G
authors.initials: CG
authors.lastname: Maher
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center, PO box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: B W
authors.initials: BW
authors.lastname: Koes
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004008:Diclofenac / Q000627:therapeutic use*; D037001:Directive Counseling; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D011320:Primary Health Care; D012107:Research Design
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D000082:Acetaminophen
keywords: Acetaminophen; Analgesics; Anti-inflammatory agents; Clinical trial; Diclofenac; General practice; General practitioners; Low back pain; Non-steroidal; Pain; Randomized controlled trial; Therapy