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Trials
Published in: Trials 1/2023

Open Access 01-12-2023 | Opioids | Study protocol

A double-blinded, placebo-controlled, randomized study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain: a study protocol

Authors: Ian A. Jones, Amit S. Piple, Pui Yuk Yan, Donald B. Longjohn, Paul K. Gilbert, Jay R. Lieberman, Gligor V. Gucev, Daniel A. Oakes, Christina E. Ratto, Alexander B. Christ, Nathanael D. Heckmann

Published in: Trials | Issue 1/2023

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Abstract

Background

Pain management is a critical component of comprehensive postsurgical care, as it influences patient safety and outcomes, and inadequate control has been associated with the development of chronic pain syndromes. Despite recent improvements, the management of postoperative pain following total knee arthroplasty (TKA) remains a challenge. The use of opioid-sparing, multimodal analgesic regimens has broad support, but there is a paucity of high-quality evidence regarding optimal postoperative protocols and novel approaches are needed. Dextromethorphan stands out among both well-studied and emerging pharmacological adjuncts for postoperative pain due its robust safety profile and unique pharmacology. The purpose of this study is to evaluate the efficacy of multi-dose dextromethorphan for postoperative pain control following TKA.

Methods

This is a single-center, multi-dose, randomized, double-blinded, placebo-controlled trial. A total of 160 participants will be randomized 1:1 to receive either 60 mg oral dextromethorphan hydrobromide preoperatively, as well as 30 mg 8 h and 16 h postoperatively, or matching placebo. Outcome data will be obtained at baseline, during the first 48 h, and the first two follow-up visits. The primary outcome measure will be total opioid consumption at 24 h postoperatively. Secondary outcomes related to pain, function, and quality of life will be evaluated using standard pain scales, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) questionnaire, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, and clinical anchors.

Discussion

This study has a number of strengths including adequate power, a randomized controlled design, and an evidence-based dosing schedule. As such, it will provide the most robust evidence to date on dextromethorphan utilization for postoperative pain control following TKA. Limitations include not obtaining serum samples for pharmacokinetic analysis and the single-center study design.

Trial registration

This trial has been registered on the National Institute of Health’s ClinicalTrials.​gov (NCT number: NCT05278494). Registered on March 14, 2022.
Appendix
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Metadata
Title
A double-blinded, placebo-controlled, randomized study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain: a study protocol
Authors
Ian A. Jones
Amit S. Piple
Pui Yuk Yan
Donald B. Longjohn
Paul K. Gilbert
Jay R. Lieberman
Gligor V. Gucev
Daniel A. Oakes
Christina E. Ratto
Alexander B. Christ
Nathanael D. Heckmann
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-023-07240-0

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