CARES Trial Protocol Published in BMJ Open

We are excited to share that the protocol for the CARES Trial (Comparing Analgesic Regimen Effectiveness and Safety after Surgery) has been published in BMJ Open. This publication is an important milestone in making our study design and goals transparent to the global research and clinical community.

CARES is a pragmatic, international, multicenter randomized controlled trial designed to answer a fundamental question: which pain medicines are safest and most effective after outpatient surgery? The trial is enrolling adults undergoing three common procedures—laparoscopic cholecystectomy, inguinal hernia repair, and breast lumpectomy—and randomizing participants to one of two discharge regimens:

• NSAID regimen plus acetaminophen

• Low-dose opioid regimen (10 pills of oxycodone 5 mg or equivalent) plus acetaminophen

Participants are followed for up to six months after surgery, with outcomes including pain, side effects, quality of recovery, sleep, mental health, and risk of prolonged opioid use. With a target enrollment of about 900 participants across North America, CARES will generate urgently needed evidence to inform safer and more effective pain management after surgery.

Why This Matters

After surgery, patients want good pain relief without unnecessary risks. Yet doctors often don’t have clear answers about which medicines are best to prescribe—opioids or non-opioid options. The CARES Trial is designed to close this gap by directly comparing these approaches in everyday surgical patients. The results will help patients recover with less pain, fewer side effects, and lower risk of long-term problems.

Centering Patients and Stakeholders

A defining feature of CARES is its patient-centered approach. Among the protocol authors, Mary Neff serves as a community stakeholder and Rachel McDuffie is a lead patient stakeholder for the study. Their leadership reflects PCORI’s emphasis on patient-centered outcomes research and ensures that the trial addresses the questions and outcomes that matter most to patients and families.

“As a community stakeholder, my goal is to make sure the voices of patients and families are part of every step of this research. Publishing the CARES protocol is exciting because it shows how seriously the team takes transparency and patient-centeredness. This trial isn’t just about comparing medicines—it’s about improving recovery in ways that matter most to people’s everyday lives.”

— Mary Neff, Community Stakeholder, CARES Trial

Looking Ahead

Publishing the protocol in BMJ Open reinforces our commitment to transparency and trustworthiness in research. We are grateful to our investigators, site teams, patient partners, and—most importantly—the patients who make this trial possible.

Read the full protocol at BMJ Open.

The CARES Trial is funded by the Patient-Centered Outcomes Research Institute (PCORI).