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

Study Overview
=================
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.

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

Conditions
-----------------
Surgery, Pain, Postoperative

Intervention / Treatment
-----------------
* Drug: NSAID
* Drug: Opioid
* Drug: Acetaminophen


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast lumpectomy, Medications after surgery, NSAIDS, Acetaminophen, Opioids, laparoscopic gallbladder removal, inguinal hernia repair, Analgesics, non-narcotic