Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES): protocol for a pragmatic, international multicentre randomised trial.

Abstract

Introduction: Acute pain is commonly experienced by millions of patients who undergo outpatient surgical procedures. Moreover, an increasing number of procedures are performed on an outpatient basis, requiring greater postoperative planning to ensure effective pain management. Analgesic approaches commonly involve prescription opioids and non-steroidal anti-inflammatory drugs (NSAIDs), but an optimal regimen that balances pain and adverse effects has not been identified. In addition, critical gaps in evidence exist regarding how opioids and NSAIDs compare as analgesic regimens after surgery.

Methods and analysis: The Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES) trial is a pragmatic, international, multicentre randomised trial that enrols adults undergoing three elective surgical procedures (laparoscopic cholecystectomy, breast lumpectomy, hernia repair). Participants are randomised to receive discharge analgesic prescriptions that consist of either NSAIDs or low-dose opioids (ie, 10 pills of oxycodone 5 mg or equivalent), with both groups prescribed acetaminophen around-the-clock. The primary effectiveness outcome is patient-reported worst daily pain intensity over the first 7 days after surgery. The primary safety outcome is the occurrence of opioid and/or NSAID side effects over the first 7 days after surgery. Secondary outcomes are assessed by patient report and medical record review at 1 week, 1 month, 3 months and 6 months after surgery and include sleep disturbance, patient perception of improvement/change after treatment, pain interference, anxiety, depression, health-related quality of life, clinically important adverse events, substance use, opioid misuse, chronic pain, healthcare utilisation related to pain and quality of recovery.

Ethics and dissemination: Investigational review boards at the University of Michigan and other sites have approved the CARES trial. The first patient enrolled in CARES in February 2023, with recruitment anticipated through 2026. Dissemination builds on the input of patient partners and other members of an engaged Stakeholder Advisory Board, with activities spanning co-production of summaries to share results with study participants, publications in biomedical journals and lay press, presentations to scientific and community organisations, and other multimedia communication materials.

Trial registration number: NCT05722002.