Abstract ID: A30

Abstract Title: Effect of perioperative rofecoxib therapy on the efficacy and safety of the fentanyl HCl patient-activated transdermal system (fentanyl HCl PATS) and intravenous patient-controlled analgesia (IV PCA) with morphine following total hip replacement

Authors: Hartrick C1, Bourne M2, Damaraju C3, Hewitt D4
         William Beaumont Hospital Royal Oak MI USA1, Lifetree Clinical Research Salt Lake City UT USA2, Ortho-McNeil Janssen Scientific Affairs, LLC Raritan NJ USA3, Pricara, A Unit of Ortho-McNeil, Inc. Raritan NJ USA4
Poster Type: Either


ABSTRACT BODY

Introduction: A novel, needle-free, compact, iontophoretic fentanyl HCl patient-activated transdermal system (PATS) was compared to a standard regimen of morphine intravenous patient-controlled analgesia (IV PCA) for acute pain management following total hip replacement; this analysis evaluated the effect of rofecoxib on the safety and efficacy.
Materials and Methods: Analysis of a multicenter (52 sites), open-label, randomized, active control, parallel-group, phase IIIb trial of patients who underwent hip replacement. Patients were titrated to comfort with IV opioids and randomized 1:1 to receive PATS (40 μg fentanyl [10-min infusion/lock-out]; 6 doses/h max) or IV PCA (1-mg morphine bolus dose [5-min lock-out]; 10 mg/h max) for up to 72 h. All patients enrolled prior to its withdrawal from the market received rofecoxib 25 mg 2-4 h before surgery and on each postoperative day. Supplemental analgesia (IV fentanyl or morphine) was available during the first 3 h of treatment. The primary efficacy endpoint was success ("good" or "excellent" ratings) on the patient global assessment (PGA) of the method of pain control in the first 24 h ("excellent," "good," "fair," or "poor"). Secondary endpoints included the mean last 24-h pain intensity score (numerical scale, 0-10) and discontinuation rate. Equivalence on the PGA required the 95% CI for the difference in PGA success rates to be within ±10%; equivalence on pain intensity required the difference in the mean last 24-h pain intensity scores to fall within ±1. Adverse events (AEs) were assessed.
Results: Similar proportions of patients in the PATS and IV PCA groups were treated with (n=193 and n=188) or without (n=202 and n=216) rofecoxib, respectively. Between-group 24-h PGA success rates and mean last 24-h pain intensity scores were equivalent with or without rofecoxib (Table). Among patients not receiving rofecoxib, significantly more patients discontinued due to inadequate analgesia in the PATS group. Among patients receiving rofecoxib, significantly more patients discontinued due to AEs in the IV PCA group (Table). Also, the effect of interaction between treatment and rofecoxib on the discontinuations due to AEs was significant (P<0.1). A lower incidence of several AEs was reported in patients receiving PATS with rofecoxib than IV PCA with rofecoxib: hypotension, 6.7% vs 16.5%; nausea, 28.0% vs 44.7%; vomiting, 9.3% vs 17.0%; pruritus, 3.6% vs 10.6%; urinary retention, 1.6% vs 3.7%; and hypoxia, 5.2% vs 6.9%. In contrast, the incidence of these AEs was generally similar in patients not receiving rofecoxib in the PATS and IV PCA groups, respectively: hypotension, 7.9% vs 8.3%; nausea, 32.2% vs 31.5%; vomiting, 11.9% vs 10.2%; pruritus, 4.0% vs 6.5%; urinary retention, 3.5% vs 6.0%; and hypoxia, 6.4% vs 6.9%.
Conclusions: Findings demonstrated PATS to be similar in efficacy to morphine IV PCA for acute pain management following hip replacement with or without rofecoxib. The AE profile of PATS with rofecoxib was generally better than that of IV PCA with rofecoxib. These results indicate that there may be important safety differences between combination analgesic regimens in postoperative patients.
Acknowledgment: Supported by Ortho-McNeil, Inc.

ATTACHED FILES

A30_Table for submission.doc





Reg Anesth Pain Med 2005; 30(3):A30