Pregabalin naproxencarbil in acute post-bunionectomy pain: a randomized clinical trial.

Abstract

Introduction: Practice guidelines recommend multimodal approaches for better management of acute pain including the administration of two or more drugs that act by different analgesic mechanisms.

Objective: The study aimed to assess pregabalin naproxencarbil (PNC), a new chemical entity targeting both nociceptive and neuropathic pain pathways, for the management of acute pain.

Methods: This randomized, double-blind, placebo-controlled trial enrolled 450 participants scheduled for first metatarsal bunionectomy. Participants were randomized (1:1:1) to receive either 1250 mg or 750 mg of PNC or placebo. Study drug was administered 1 hour before surgery and thereafter every 12 hours for 72 hours. Participants reported numeric pain rating scale to calculate summed pain intensity (SPI). Rescue pain medication use and safety were monitored.

Results: The least-squares mean (LSM) (SE) of SPI over 48 hours (SPI48) for the 1250 mg PNC group vs placebo as the primary efficacy end point was 132.6 (8.0) vs 286.0 (8.2) (P < 0.0001). For the 750 mg group vs placebo as the key secondary efficacy end point, the LSM (SE) of SPI48 was 157.9 (8.3) vs 289.5 (8.5) (P < 0.0001). Rescue medication was spared by 42.8%, 33.6%, and 2.7% participants in the 1250 mg, 750 mg, and placebo groups, respectively. Hazard ratios (95% confidence interval) for time to initiate rescue medication were 0.18 (0.14-0.25) for 1250 mg vs placebo and 0.24 (0.18-0.31) for 750 mg vs placebo. Tramadol consumption over 72 hours in the placebo was 4.1- or 3.0-fold higher than in the 1250 mg or 750 mg groups, and 3- or 2.5-fold higher with acetaminophen. Mild somnolence, dizziness, nausea, and constipation were more common in active groups.

Conclusion: Pregabalin naproxencarbil dose-dependently reduced acute postoperative pain with acceptable safety profiles.

Trial registration: ClinicalTrials.gov Identifier: NCT06017999.