Non-opioid analgesics: other: Multiple dose efficacy of the parenteral specific COX-2 inhibitor, parecoxib sodium, following bunionectomy surgery

Abstract

This randomized, single- and double-blind phase, placebo-controlled trial evaluated the analgesic efficacy/safety of parecoxib in patients after bunionectomy surgery. Single-blind phase: on the day of surgery (Day 1) all patients (n=454) received two doses; a first dose of parecoxib 40mg IV within 8h of surgery when pain intensity (PI) was moderate/severe (categorical scale) and ≥45mm (VAS scale), and a second dose of parecoxib 20mg IV within 1-12h of the first dose. Double-blind phase (Day 2-3): Patients were randomized to parecoxib 20mg bid, 20mg qd/placebo, or placebo bid. Patients were allowed rescue medication (hydrocodone 5mg/acetaminophen 500mg tablets) after the second dose of study medication on each day of the double-blind phase, but all were re-entered into the study at 08:00h the next day to receive assigned study medication after a baseline pain assessment. Efficacy measures: PI (categorical and VAS) was assessed at 4, 8, 12, and 16h after morning dose, and immediately prior to morning dose on the following day. Patient's Global Evaluation of Study Medication, and time to rescue medication were also recorded. On Days 2&3, summed PI and time-specific PI (categorical and VAS), Patient's Global Evaluation, and time to rescue medication were significantly improved in both parecoxib groups vs placebo (P<0.001). Parecoxib 20mg bid demonstrated statistically significant improvements over parecoxib 20mg qd in summed PI (VAS) and time to rescue medication on Day 3 (P<0.001) but not Day 2. The incidence of adverse events was significantly lower in both parecoxib regimens compared with placebo (P<0.05). Parecoxib 20mg qd was efficacious and well tolerated compared with placebo in treating postbunionectomy pain. The data also suggest that a second 20-mg dose of parecoxib/day may provide improved efficacy for some patients. The magnitude of analgesia was sustained and improving over several days of parecoxib therapy. Supported by Pfizer Inc.