Efficacy and Safety of an Intravenous Acetaminophen/Ibuprofen Fixed-dose Combination After Bunionectomy: a Randomized, Double-blind, Factorial, Placebo-controlled Trial

Abstract

Purpose: Multimodal analgesia with acetaminophen and/or nonsteroidal anti-inflammatory drugs is recommended for the treatment of postoperative pain. Although oral fixed-dose combinations (FDCs) are available, parenteral administration may be clinically justified. The goal of this study was to investigate the clinical efficacy and safety of an intravenous FDC of ibuprofen and acetaminophen after bunionectomy. Methods: This study was a prospective, randomized, double-blind, multicenter, placebo-controlled factorial clinical trial conducted at 2 clinical research centers in the United States between November 2016 and June 2017. Eligible patients (male and female subjects, aged 18e65 years, reporting pain intensity levels 40 mm on a 100-mm visual analog scale (VAS) after distal, first metatarsal bunionectomy) were randomized (3:3:3:2) to receive the FDC (ibuprofen 300 mg + acetaminophen 1000 mg), ibuprofen 300 mg, acetaminophen 1000 mg, or placebo (vehicle), administered as 15-minute intravenous infusions every 6 hours for 48 hours. The primary efficacy end point was the time-adjusted sum of pain intensity differences from baseline over 48 hours (SPID 48). In addition to VAS pain intensity scores, pain relief scores, time to perceptible and meaningful pain relief, the use of rescue medication, and participant's global evaluations of the study drug were recorded. Adverse events occurring during the 48-hour treatment period were included in the safety analysis. Findings: A total of 276 participants were enrolled; most were female (82%), the mean age was 42.4 years, and the median baseline VAS was 67 mm, indicating moderate to severe pain. SPID 48 was significantly higher for the FDC (23.4 [2.5] mm) than for ibuprofen (9.5 [2.5] mm), acetaminophen (10.4 [2.5] mm), and placebo (−1.3 [3.1] mm; all, P < 0.001). The superior analgesic effect of the FDC was supported by a range of secondary end points, including reduced opioid usage rates (75% for FDC, 92% for ibuprofen, 93% for acetaminophen, and 96% for placebo; all, P < 0.005). The safety profile of the FDC was comparable to that of intravenous ibuprofen or acetaminophen alone. Three participants withdrew from the study due to adverse events: 2 in the ibuprofen group and 1 in the acetaminophen group. Implications: The study found that repeated administration of an intravenous FDC of ibuprofen and acetaminophen provided statistically significant improvement in SPID 48 over comparable doses of either monotherapy without an increase in adverse events. ClinicalTrials.gov identifier: NCT02689063.

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“…A multisite randomized controlled trial by Gupta and colleagues in 74 patients having elective hip or knee arthroplasty found that, compared with administering IV ibuprofen alone, giving patients both drugs at the start of surgery and then every six hours until discharge for up to five days significantly lowered verbal pain scores and opioid consumption 23. A prospective, double-blind, randomized controlled trial by Daniels and colleagues yielded similar findings 20. In that study, patients who received IV ibuprofen and IV acetaminophen reported better pain scores and used less opioids than those receiving either drug alone.…”

PROSPECT guideline for hallux valgus repair surgery: a systematic review and procedure‐specific postoperative pain management recommendations

“…One trial of 276 patients showed that the combination of ibuprofen and paracetamol reduced pain scores and opioid consumption during the first 48 postoperative hours when compared with placebo, ibuprofen, or paracetamol. 20 …”

“…23 29 One trial of 276 patients showed that the combination of ibuprofen and paracetamol reduced pain scores and opioid consumption during the first 48 postoperative hours when compared with placebo, ibuprofen, or paracetamol. 20 steroids Two trials compared the administration of steroids with placebo. 6 40 In one study (n=78), the intervention group received intramuscular betamethasone 12 mg 30 min before the surgery, 6 and in the other (n=60) oral dexamethasone 9 mg 60 min before and 24 hours after the surgery.…”

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