Effect of Combination of Paracetamol (Acetaminophen) and Ibuprofen vs Either Alone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty: The PANSAID Randomized Clinical Trial

IMPORTANCE: Multimodal postoperative analgesia is widely used but lacks evidence of benefit. OBJECTIVE: Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018. INTERVENTIONS: Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS–PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery. MAIN OUTCOMES AND MEASURES: Two co–primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P