SurgeryPhase 4CARESNCT05722002
Comparing Analgesic Regimen Effectiveness and Safety for Surgery (CARES) Trial
A Phase 4 study testing NSAID, Opioid and Acetaminophen in people with Surgery and Pain, Postoperative, run by University of Michigan at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Surgery, Pain, Postoperative
- What is being tested?
- NSAID, Opioid and Acetaminophen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 6 Feb 2023to 31 Aug 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 2 countries
United States6 sites, 6 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Sarah Clark, 734-232-0324, sarahmcl@med.umich.edu
Mark Bicket, MD, PhD
- Recruiting
Cooper University Health Care
Camden, New Jersey, 08103
Asia Vincent, 800-826-6737, vincent-asia@CooperHealth.edu
Ludmil Mitrev, MD
- Recruiting
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27599
Karen Van Manen, PhD, 919-843-6572, karen_vanmanen@med.unc.edu
Matthew Mauck, MD, PhD
- Recruiting
Henry Ford Health System
Detroit, Michigan, 48202
Kasia Nowak, PhD, 313-771-7128, knowak2@hfhs.org
Kellie McFarlin, MD, FACS
- Recruiting
Temple University - Temple Health
Philadelphia, Pennsylvania, 19140
Anamarys Arroyo-Lloret, 215-643-5067, anamarys.arroyo-lloret@tuhs.temple.edu
Ellen Hauck, DO
- Recruiting
Washington University in Saint Louis
St Louis, Missouri, 63130
Justin Stout, MS, 314-273-2455, justinjstout@wustl.edu
Simon Haroutounian, PhD, MSc
Canada2 sites, 2 recruiting
- Recruiting
Women's College Hospital
Toronto, Ontario, M5S 1B2
Didem Bozak, 416-323-6008, didem.bozak@wchospital.ca
Karim Ladha, MD, MSc, AB, FRCPC
- Recruiting
Unity Health Toronto
Toronto, Ontario
Janneth P Canizares, 416-864-6060, janneth.pazmino-canizares@unityhealth.to
Duminda Wijeysundera, MD, PhD
About this study
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
- Being tested
- NSAID, Opioid, Acetaminophen
- Keywords
- Medications after surgery, NSAIDS, Acetaminophen, Opioids, laparoscopic gallbladder removal, inguinal hernia repair, breast lumpectomy, Analgesics, non-narcotic
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NSAIDDrug
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)
OpioidDrug
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
AcetaminophenDrug
Acetaminophen 1000 mg by mouth every 6 hours around the clock for the first three days after surgery then as needed thereafter (20 doses).
| Study group | Role | What they receive |
|---|---|---|
| NSAID regimen | Other | Surgical teams will elect for one of the medications within the treatment arm to which the patient is randomized. Receives: Drug: NSAID; Drug: Acetaminophen |
| Opioid regimen | Other | Not described Receives: Drug: Opioid; Drug: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 7 days post surgery
Secondary outcomes (16)
Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance v1.0 4a questionnaire
This is a 4 question survey in which participants will rate statements pertaining to quality of sleep.
Participants will also rate sleep quality as very poor (5), poor (4), fair (3), good (2), or very good (1).
Measured: 1 month post surgery
Clinically important adverse events
The study team will review charts for unplanned postoperative clinical interactions related to pain (patient messages, phone calls, non-routine clinic visits related to pain) and emergency room visits, hospitalizations, and 30-day complications after discharge measured using the American College of Surgeons' (ACS) National Surgical Quality Improvement Program (NSQIP) definitions.
Measured: 180 days post surgery
Patient Global Impression of Change (PGIC)
The perception of improvement after treatment will be assessed by the patient global impression of change PGIC (range 0-7).
Measured: up to 1 month after surgery
Quality of Recovery (QoR) 15
There are 15 questions assessed on a scale of 1-10, with 0 being none of the time and 10 being all of the time, 10 being the better outcome.
Measured: 3 days post surgery
Quality of Recovery (QoR) 15
There are 15 questions assessed on a scale of 1-10, with 0 being none of the time and 10 being all of the time, 10 being the better outcome.
Measured: 7 days post surgery
PROMIS Pain Interference 4a
This is a 4 question survey that assesses the degree to which pain interferes with various aspects of life. Items are scored on a 1 ("Not at all") to 5 ("Very much") scale with a range of 4 - 20. Higher scores indicate greater pain interference.
Measured: 3 months
PROMIS Preference score 29+2 Profile v2.1
This is a 31 question survey that includes questions to evaluate each of 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, social functioning, and pain interference) using a 5- point Likert scale, as well as a single item to assess pain severity on a 0-10 scale as well as 2 questions for cognitive function. Higher scores are indicative of better health.
Measured: 3 months
Substance use based on the Tobacco, Alcohol, Prescription medications, and other Substance (TAPS) tool
This National Institute on Drug Abuse (NIDA) TAPS tool has part 1 (5 questions) and part 2 (possible 9 questions).
Measured: 180 days post surgery
National Survey on Drug Use and Health Questions (NSDUH) on Opioid Misuse opioid misuse question
Measured: 3 months
National Survey on Drug Use and Health Questions (NSDUH) on Opioid Misuse opioid misuse question
Measured: 180 days
New prolonged opioid use
This will include greater or equal to 1 opioid prescription post-discharge between 4-180 days post discharge.
Measured: days 4-180 post surgery
Chronic pain based on Brief Pain Inventory (BPI) pain intensity score at 180 days post surgery
One question survey in which the participants rate pain intensity recorded (0-10), ten being the worst.
Measured: 180 days post surgery
Chronic pain based on Body Map
Participants will document/mark on this image map to identify areas in which persistent or recurrent pain was felt.
Measured: 180 days post surgery
Acute pain based on The Michigan Body Map
Participants will document/mark on this image map to identify areas in which persistent or recurrent pain was felt.
Measured: 7 days post surgery
Healthcare Utilization related to pain at 1 month
Participants will answer questions about their healthcare utilization related to pain for the time period from date of surgery to one month later for the following three events: (1) postoperative clinical interactions related to pain in the form of patient messages, phone calls, and non-routine clinic visits related to pain, (2) emergency room visits, and (3) hospitalizations. The study team will also review health record for the same events.
Measured: within 1 months after surgery
Healthcare Utilization related to pain at 6 months
Participants will answer questions about their healthcare utilization related to pain for the time period from date of surgery to six months later related to pain for the following three events: (1) postoperative clinical interactions in the form of patient messages, phone calls, and non-routine clinic visits related to pain, (2) emergency room visits, and (3) hospitalizations. The study team will also review health record for the same events.
Measured: within 6 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start6 Feb 2023
- Primary completion10 Feb 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SurgeryStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Mark Bicket, MD, PhD, University of Michigan
- Investigators
- Mark Bicket, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05722002
- Sponsor's protocol ID
- HUM00215416
- Other IDs
- CER-2021C1-22398
- Acronym
- CARES
- Status last verified
- Aug 2026
- First submitted
- 30 Jan 2023
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results of the trial that is not subject to restrictions based on data sharing agreements (e.g., prescription drug monitoring program data), after deidentification.
Publications
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.
PubMed 40187774