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

Sponsor

University of Michigan (Other)

Overall Status

Recruiting

CT.gov ID

NCT05722002

Collaborator

Patient-Centered Outcomes Research Institute (Other)

900

Enrollment

Locations

Arms

19.8

Anticipated Duration (Months)

225

Patients Per Site

11.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Surgery Pain, Postoperative	Drug: NSAID Drug: Opioid Drug: Acetaminophen	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

900 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Outcomes Assessor)

Masking Description:

Both study staff performing outcome assessment and data analysis will be masked to treatment assignment.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 6, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

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: 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 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).

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: 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

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).

Outcome Measures

Primary Outcome Measures

Pain intensity based on Brief Pain Inventory (BPI) pain intensity score at the surgical site over 7 days post surgery [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.
Safety outcome - number and severity of any adverse medication-related symptoms over 7 days post surgery [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.

Secondary Outcome Measures

Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance v1.0 4a questionnaire [1 month post surgery]
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).
Clinically important adverse events [180 days post surgery]
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.
Patient Global Impression of Change (PGIC) [up to 1 month after surgery]
The perception of improvement after treatment will be assessed by the patient global impression of change PGIC (range 0-7).
Quality of Recovery (QoR) 15 [3 days post surgery]
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.
Quality of Recovery (QoR) 15 [7 days post surgery]
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.
PROMIS Pain Interference 4a [3 months]
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.
PROMIS Preference score 29+2 Profile v2.1 [3 months]
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.
Substance use based on the Tobacco, Alcohol, Prescription medications, and other Substance (TAPS) tool [180 days post surgery]
This National Institute on Drug Abuse (NIDA) TAPS tool has part 1 (5 questions) and part 2 (possible 9 questions).
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 [days 4-180 post surgery]
This will include greater or equal to 1 opioid prescription post-discharge between 4-180 days post discharge.
Chronic pain based on Brief Pain Inventory (BPI) pain intensity score at 180 days post surgery [180 days post surgery]
One question survey in which the participants rate pain intensity recorded (0-10), ten being the worst.
Chronic pain based on Body Map [180 days post surgery]
Participants will document/mark on this image map to identify areas in which persistent or recurrent pain was felt.
Acute pain based on The Michigan Body Map [7 days post surgery]
Participants will document/mark on this image map to identify areas in which persistent or recurrent pain was felt.
Healthcare Utilization related to pain at 1 month [within 1 months after surgery]
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.
Healthcare Utilization related to pain at 6 months [within 6 months after surgery]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109
2	Henry Ford Health System	Detroit	Michigan	United States	48202
3	Washington University in Saint Louis	Saint Louis	Missouri	United States	63130
4	Unity Health Toronto	Toronto	Ontario	Canada