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.

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.

Rapid Adaptation of a Surgical Research Unit to Conduct Clinical Trials During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has brought most ongoing clinical trials to a standstill, while at the same time emphasizing the need for new therapeutic treatments and strategies to mitigate the morbidity and mortality related to COVID-19. Recent publication of several observational studies has generated much discussion surrounding efficacy of drugs including hydroxychloroquine, azithromycin, and remdesivir, stressing the need for high-quality prospective, randomized control trials in patients with COVID-19. Ongoing "stay at home" orders and institutional policies mandating "work from home" for nonessential employees, which includes most research personnel, have impacted the ability to implement and conduct clinical studies. This article discusses the approach of an experienced clinical trials unit to make adjustments for ongoing studies and ensure the safety of study participants. At the same time, plans were implemented to continue collection of data to achieve endpoints, safely enroll and follow participants in studies offering potential benefit, and quickly implement new COVID-19 clinical trials. The existence of a Division of Clinical Research with regulatory, budgeting, contracting, and coordinating expertise within a department of surgery can successfully accommodate a crisis situation and rapidly adapt to new requirements for the safe, efficient, and effective conversion to a remote work force without compromising the research process.