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

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.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Surgery
• Intervention / Treatment: Drug: NSAID; Drug: Acetaminophen; Drug: Opioid

• Study Type: Interventional
• Enrollment (Estimated): 900
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kendall Dubois, MS; Phone Number: 734-232-0324; Email: kendalld@med.umich.edu

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Not yet recruiting
      • Unity Health Toronto
      • Contact: Janneth P Canizares; Phone Number: 416-864-6060; Email: janneth.pazmino-canizares@unityhealth.to
      • Principal Investigator: Karim Ladha, MD, MSc, FRCPC
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Mark Bicket, MD, PhD
      • Contact: Kendall Dubois; Phone Number: 734-232-0324; Email: kendalld@med.umich.edu
    • Detroit, Michigan, United States, 48202
      • Not yet recruiting
      • Henry Ford Health System
      • Contact: Kelly Marsack; Phone Number: 313-916-2600; Email: kmarsac1@hfhs.org
      • Principal Investigator: Kellie McFarlin, MD, FACS
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Not yet recruiting
      • Washington University in Saint Louis
      • Contact: Justin Stout, PhD, MSc; Phone Number: 314-273-2455; Email: justinjstout@wustl.edu
      • Principal Investigator: Simon Haroutounian, PhD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: NSAID regimen; Surgical teams will elect for one of the medications within the treatment arm to which the patient is randomized.	Drug: NSAID; 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); Drug: Acetaminophen; Acetaminophen 1000 mg by mouth every 6 hours around the clock for the first three days after surgery then as needed thereafter (20 doses).
Other: Opioid regimen	Drug: Acetaminophen; Acetaminophen 1000 mg by mouth every 6 hours around the clock for the first three days after surgery then as needed thereafter (20 doses).; Drug: Opioid; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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).	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.	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.	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.	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.	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).	180 days post surgery
National Survey on Drug Use and Health Questions (NSDUH) on Opioid Misuse opioid misuse question		3 months
National Survey on Drug Use and Health Questions (NSDUH) on Opioid Misuse opioid misuse question		180 days
New prolonged opioid use	This will include greater or equal to 1 opioid prescription post-discharge between 4-180 days post discharge.	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.	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.	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.	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.	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.	within 6 months after surgery

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Mark Bicket, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 9, 2023
• First Posted (Actual): February 10, 2023

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Acetaminophen; Opioids; inguinal hernia repair; NSAIDS; Medications after surgery; breast lumpectomy; laparoscopic gallbladder removal; Analgesics, non-narcotic
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: HUM00215416; CER-2021C1-22398 (Other Grant/Funding Number: PCORI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No