title: PANSAID - PAracetamol and NSAID in combination: study protocol for a randomised trial.
abstract: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. No 'gold standard' exists after total hip arthroplasty (THA) and combinations of different nonopioid medications are used with virtually no evidence for additional analgesic efficacy compared to monotherapy. The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen alone and in combination in different dosages after THA.
  
  
  
  PANSAID is a placebo-controlled, parallel four-group, multicentre trial with centralised computer-generated allocation sequence and allocation concealment and with varying block size and stratification by site. Blinding of assessor, investigator, caregivers, patients and statisticians. Patients are randomised to four groups: (A) paracetamol 1 g × 4 and ibuprofen 400 mg × 4, (B) paracetamol 1 g × 4 and placebo, (C) placebo and ibuprofen 400 mg × 4 and (D) paracetamol 0.5 g × 4 and ibuprofen 200 mg. The two co-primary outcomes are 24-h consumption of morphine and number of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and number of patients with one or more adverse events within 24 h postoperatively. Inclusion criteria are patients scheduled for unilateral, primary THA; age above 18 years; ASA status 1-3; BMI >18 and <40 kg/m2; women must not be pregnant; and provision of informed consent. Exclusion criteria are patients who cannot cooperate with the trial; participation in another trial; patients who cannot understand/speak Danish; daily use of strong opioids; allergy against trial medication; contraindications against ibuprofen; alcohol and/or drug abuse. A total of 556 eligible patients are needed to detect a difference of 10 mg morphine i.v. the first 24 h postoperatively with a standard deviation of 20 mg and a family wise type 1 error rate of 0.025 (two-sided) and a type 2 error rate of 0.10 for the six possible comparisons of the four intervention groups.
  
  
  
  We started recruiting patients in December 2015 and expect to finish in September 2017. Data analysis will be from September 2017 to October 2017 and manuscript submission ultimo 2017.
  
  
  
  EudraCT: 2015-002239-16 (12/8-15); ClinicalTrials.gov: NCT02571361 . Registered on 7 October 2015.
authors.affiliation: Department of Anaesthesiology, Næstved Hospital, Ringstedgade 61, 4700, Næstved, Denmark. khty@regionsjaelland.dk.
authors.forename: Kasper Højgaard
authors.initials: KH
authors.lastname: Thybo
authors.affiliation: Department of Anaesthesiology, Næstved Hospital, Ringstedgade 61, 4700, Næstved, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hägi-Pedersen
authors.affiliation: Copenhagen Trial Unit, Rigshospitalet, Department 7812, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Department of Anaesthesiology, Bispebjerg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen, NV, Denmark.
authors.forename: Jørgen Berg
authors.initials: JB
authors.lastname: Dahl
authors.affiliation: Department of Orthopedic Surgery, Næstved Hospital, Ringstedgade 61, 4700, Næstved, Denmark.
authors.forename: Henrik Morville
authors.initials: HM
authors.lastname: Schrøder
authors.affiliation: Department of Anaesthesiology, Holbæk Hospital, Smedelundsgade 60, 4300, Holbæk, Denmark.
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Bülow
authors.affiliation: Department of Orthopedic Surgery, Nykøbing Falster Hospital, Fjordvej 15, 4800, Nykøbing Falster, Denmark.
authors.forename: Jan Gottfrid
authors.initials: JG
authors.lastname: Bjørck
authors.affiliation: Department of Anaesthesiology, Zealand University Hospital Køge, Lykkebækvej 1, 4600, Køge, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mathiesen
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002985:Clinical Protocols; D004359:Drug Therapy, Combination; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D010149:Postoperative Pain / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D007052:Ibuprofen
keywords: Benefit; Harm; Ibuprofen; Multimodal analgesia; Paracetamol; Postoperative pain; Total hip arthroplasty