Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind, randomized, placebo-controlled phase III study.

Abstract

OBJECTIVE:

To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively.

RESEARCH DESIGN AND METHODS:

In this double-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n = 144), etoricoxib 90 mg/day (n = 142), or etoricoxib 120 mg/day (n = 144). Average Pain Intensity at Rest over days 1-3 (0- to 10-point numerical rating scale [NRS]) was the primary efficacy endpoint. Secondary endpoints included Average Pain Intensity upon Sitting, Standing, and Walking over days 1-3 (0- to 10-point NRS) as well as Average Total Daily Dose of Morphine over days 1-3.

CLINICAL TRIAL REGISTRATION:

This trial is registered on www.clinicaltrials.gov (NCT00788710).

RESULTS:

The least squares (LS) means (95% CI) for the primary endpoint were 3.26 (2.96, 3.55); 2.46 (2.16, 2.76); and 2.40 (2.11, 2.69) for placebo, etoricoxib 90 mg, and etoricoxib 120 mg, respectively, significantly different for both etoricoxib doses versus placebo (p < 0.001). Patients on etoricoxib 90 mg and 120 mg required ~30% less morphine per day than those on placebo (p < 0.001), which led to more rapid bowel recovery in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain ≤3/10.

LIMITATIONS:

A key limitation for this study was that movement-evoked pain measurements were not designated as primary endpoints.

CONCLUSION:

In patients undergoing total abdominal hysterectomy, etoricoxib 90 mg and 120 mg dosed preoperatively and then continued postoperatively significantly reduces both resting and movement-related pain, as well as reduced opioid (morphine) consumption that led to more rapid bowel recovery.

• Authors: Eugene R Viscusi, Tara L Frenkl, Craig T Hartrick, Narinder Rawal, Henrik Kehlet, Dimitris Papanicolaou, Arnold Gammaitoni, Amy T Ko, Leslie M Morgan, Anish Mehta, Sean P Curtis, Paul M Peloso
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 28 Issue 8 Pg. 1323-35 (Aug 2012) ISSN: 1473-4877 [Electronic] England
• PMID: 22738802 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Analgesics, Opioid
• Cyclooxygenase 2 Inhibitors
• Placebos
• Pyridines
• Sulfones
• Etoricoxib

Topics

• Abdomen (surgery)
• Adult
• Aged
• Analgesics (administration & dosage, adverse effects)
• Analgesics, Opioid (administration & dosage, adverse effects)
• Cyclooxygenase 2 Inhibitors (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Etoricoxib
• Female
• Humans
• Hysterectomy (adverse effects, methods)
• Middle Aged
• Pain, Postoperative (drug therapy)
• Perioperative Care (methods)
• Placebos
• Pyridines (administration & dosage, adverse effects)
• Sulfones (administration & dosage, adverse effects)
• Treatment Outcome