Comparing Analgesic Regimen Effectiveness and Safety for Surgery (CARES) Trial

NCT05722002 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: HUM00215416CER-2021C1-22398
• Study Type: interventional
• Target: 900
• Locations: 2 countries
• Sites: 8

Brief Summary

This trial is being completed to compare two commonly used options to treat pain after surgery. Participants that undergo gallbladder removal, hernia repair, and breast lump removal will be eligible to enroll. Eligible participants will be randomized to 1 of 2 groups of medications (Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) plus acetaminophen or low dose opioids plus acetaminophen). It is anticipated that the NSAID group will have superior clinical outcomes and fewer side effects when compared to the opioid group.

Conditions

Surgery; Pain, Postoperative

Keywords

Medications after surgery; NSAIDS; Acetaminophen; Opioids; laparoscopic gallbladder removal; inguinal hernia repair; breast lumpectomy; Analgesics, non-narcotic

Outcome Measures

Primary Outcomes (2)

• Pain intensity based on Brief Pain Inventory (BPI) pain intensity score at the surgical site over 7 days post surgery

  This is a one question survey in which the worst pain intensity recorded (0-10 being the worst) will be used.

  7 days post surgery

• Safety outcome - number and severity of any adverse medication-related symptoms over 7 days post surgery

  Symptom Checklist will proactively screen patients for reports of adverse events from analgesic medications over the first 7 days post surgery.

  7 days post surgery

Secondary Outcomes (16)

• Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance v1.0 4a questionnaire

  1 month post surgery

• Clinically important adverse events

  180 days post surgery

• Patient Global Impression of Change (PGIC)

  up to 1 month after surgery

• Quality of Recovery (QoR) 15

  3 days post surgery

• Quality of Recovery (QoR) 15

  7 days post surgery

Study Arms (2)

NSAID regimen

OTHER

Surgical teams will elect for one of the medications within the treatment arm to which the patient is randomized.

Drug: NSAID; Drug: Acetaminophen

Opioid regimen

OTHER

Drug: Opioid; Drug: Acetaminophen

Interventions

NSAID DRUG

Once randomized to this group the surgical team will elect for 1 of the following treatment options to be given: * Ibuprofen 600 milligram (mg) by mouth every six hours as needed for pain (10 doses) * Celecoxib 400 mg by mouth once then 200 mg every twelve hours as needed for pain (10 doses) * Naproxen 500 mg by mouth once then 250 mg by mouth every eight hours as needed for pain (10 doses)

NSAID regimen

Opioid DRUG

Once randomized to this group the surgical team will elect for 1 of the following treatment options to be given: * Oxycodone 5 mg by mouth every four to six hours as needed for pain, 10 doses * Morphine 7.5 mg by mouth every four to six hours as needed for pain, 10 doses * Hydromorphone 2 mg by mouth every four to six hours as needed for pain, 10 doses

Opioid regimen

Acetaminophen DRUG

Acetaminophen 1000 mg by mouth every 6 hours around the clock for the first three days after surgery then as needed thereafter (20 doses).

NSAID regimen; Opioid regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• No significant analgesic medication use before surgery: For this study, significant analgesic medication use before surgery as use of prescriptions for opioid or NSAID medications in the past 30 days, or over-the-counter NSAID use on greater than 7 of 30 past days, as reported by the patient.
• One of three common low-risk surgical procedures: For this study, the three-common low-risk surgical procedures will include laparoscopic gallbladder removal, inguinal hernia repair, and breast lumpectomy.

You may not qualify if:

• Anticipated other surgery within 6 months or anticipated life expectancy of less than 6 months
• Patients with contraindications to NSAID drugs in the NSAID arm, opioid drugs in the OPIOID arm, or acetaminophen will be excluded. There are specific contraindications that will be reviewed per protocol.

Sponsors & Collaborators

• University of Michigan: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (8)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Washington University in Saint Louis

St Louis, Missouri, 63130, United States

RECRUITING

Cooper University Health Care

Camden, New Jersey, 08103, United States

RECRUITING

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Temple University - Temple Health

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

RECRUITING

Unity Health Toronto

Toronto, Ontario, Canada

RECRUITING

Related Publications (1)

• Bicket MC, Ladha KS, Haroutounian S, McFarlin K, Neff M, McDuffie RL, Waljee JF, Wijeysundera DN, Brummet C, Li Y; CARES Investigators. Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES): protocol for a pragmatic, international multicentre randomised trial. BMJ Open. 2025 Apr 5;15(4):e099925. doi: 10.1136/bmjopen-2025-099925.

  PMID: 40187774 DERIVED

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Opioid; Acetaminophen

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Narcotics; Central Nervous System Depressants; Central Nervous System Agents; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Mark Bicket, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Clark, BA

CONTACT

734-232-0324; sarahmcl@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Both study staff performing outcome assessment and data analysis will be masked to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomization of patients will be stratified by site, sex, age (greater or equal to 65 years old), and type of surgery, via permuted block randomization with a variable block size.

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 10, 2023
• Study Start: February 6, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Anticipated summer of 2028 with no end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by a review committee and the sponsor. The type of analyses will be for analyses related to aims in the proposal. Proposals may be submitted up to 36 months after data availability, after which data will be available in the data warehouse but without investigator support.

Locations

CA (2); US (6)