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.

Key words::

• Clinical trial
• Etoricoxib
• Opioid
• Pain relief
• Perioperative
• Total abdominal hysterectomy

Transparency

Declaration of funding

This study was supported by Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.

Declaration of financial/other relationships

E.R.V., MD reports no conflicts of interest. E.R.V. reviewed and approved the final version of the paper, wrote sections of the initial draft and provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, and was involved in the conception, design, and planning of the study. T.L.F., MD, has disclosed that she is an employee of Merck Sharp & Dohme Corp. T.L.F. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, and was involved in the conception, design, and planning of the study. C.T.H., MD, reports no conflicts of interest. C.T.H. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, and interpreted the results. N.R., MD, reports no conflicts of interest. N.R. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, and interpreted the results. H.K., MD reports no conflicts of interest. H.K. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, and interpreted the results. D.P. has disclosed that he is an employee of Merck Sharp & Dohme Corp. D.P. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, and was involved in the conception, design, and planning of the study. A.G., MD has disclosed that he is a former employee of Merck Sharp & Dohme Corp. A.G. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, and interpreted the results. A.T.K., MPH, has disclosed that she is an employee of Merck Sharp & Dohme Corp. A.T.K. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, collected and assembled data, performed statistical analyses, and was involved in the conception, design, and planning of the study. L.M.M., BS, has disclosed that she is an employee of Merck Sharp & Dohme Corp. L.M.M. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, and was involved in the conception, design, and planning of the study. A.M., BA, has disclosed that he is an employee of Merck Sharp & Dohme Corp. A.M. reviewed and approved the final version of the paper, wrote sections of the initial draft, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, and interpreted the results. S.P.C., MD, has disclosed that he is an employee of Merck Sharp & Dohme Corp. S.P.C. reviewed and approved the final version of the paper, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, and was involved in the conception, design, and planning of the study. P.M.P. has disclosed that he is an employee of Merck Sharp & Dohme Corp. P.M.P., MD reviewed and approved the final version of the paper, wrote sections of the initial draft, provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript, interpreted the results, and was involved in the conception, design, and planning of the study.

CMRO peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors would like to acknowledge Martha Vollmer, MA, of Merck, for administrative and editorial support. The authors would also like to acknowledge all investigators for their involvement in the study.