Parecoxib, propacetamol, and their combination for analgesia after total hip arthroplasty: a randomized non‐inferiority trial

Background This study assessed non‐inferiority of parecoxib vs. combination parecoxib+propacetamol and compared the opioid‐sparing effects of parecoxib, propacetamol, and parecoxib+propacetamol vs. placebo after total hip arthroplasty. Methods In this randomized, placebo‐controlled, parallel‐group, non‐inferiority study, patients received one of four IV treatments after surgery: parecoxib 40 mg bid (n = 72); propacetamol 2 g qid (n = 71); parecoxib 40 mg bid plus propacetamol 2 g qid (n = 72); or placebo (n = 38) with supplemental IV patient‐controlled analgesia (morphine). Patients and investigators were blinded to treatment. Pain intensity at rest and with movement was assessed regularly, together with functional recovery (modified Brief Pain Inventory‐Short Form) and opioid‐related side effects (Opioid‐Related Symptom Distress Scale) questionnaires up to 48 h. Results After 24 h, cumulative morphine consumption was reduced by 59.8% (P < 0.001), 38.9% (P < 0.001), and 26.8% (P = 0.005) in the parecoxib+propacetamol, parecoxib, and propacetamol groups, respectively, compared with placebo. Parecoxib did not meet criteria for non‐inferiority to parecoxib+propacetamol. Parecoxib+propacetamol and parecoxib significantly reduced least‐squares mean pain intensity scores at rest and with movement compared with propacetamol (P < 0.05). One day after surgery, parecoxib+propacetamol significantly reduced opioid‐related symptom distress and decreased pain interference with function compared with propacetamol or placebo. Conclusion Parecoxib and parecoxib+propacetamol provided significant opioid‐sparing efficacy compared with placebo; non‐inferiority of parecoxib to parecoxib+propacetamol was not demonstrated. Opioid‐sparing efficacy was accompanied by significant reductions in pain intensity on movement, improved functional outcome, and less opioid‐related symptom distress. Study medications were well tolerated.