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

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

This trial is being completed to compare two commonly used options to treat pain after discharge from surgery. Participants that undergo tonsil removal, gallbladder removal, and knee scope will be eligible to enroll. Eligible participants will be randomized to prescription of 1 of 2 groups of medications (Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) plus acetaminophen or low dose opioids with the NSAIDs plus acetaminophen. The key question the study seeks to answer is which option will have the best outcomes and with the fewest side effects?

Study Overview

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

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

Contacts and Locations

• Study Contact: Name: Sarah Clark; Phone Number: 734-232-0324; Email: sarahmcl@umich.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles (CHLA)
      • Principal Investigator: Lorraine Kelley-Quon, MD
      • Contact: Nikhita Datar, MS; Phone Number: 323-361-7218; Email: ndatar@chla.usc.edu
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital Stanford
      • Principal Investigator: Jennifer Rabbitts, MD
      • Contact: Ryan Ma, BA; Phone Number: 650-665-9074; Email: ryanma@stanford.edu
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Mark Bicket, MD, PhD
      • Contact: Sarah Clark; Phone Number: 734-232-0324; Email: sarahmcl@umich.edu
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's (NCH)
      • Principal Investigator: Sara Mansfield, MD
      • Contact: Taha Akbar, BS; Phone Number: 614-355-4526; Email: taha.akbar@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• No significant analgesic medication use before surgery as defined in the protocol. For this study, we define significant analgesic medication use before surgery as prescriptions reported by the child or caregiver for 6 days or more of opioid medications in the past 90 days (aligning with American Pediatric Guidelines that were published in September 2024 after the project was funded), excepting surgical team prescriptions within the week of surgery.
• Undergo one the following: tonsil removal (with or without adenoid removal), gallbladder removal (laparoscopic), and knee scope (arthroscopy).

Exclusion Criteria:

• Anticipated other surgery within 12 months
• Anticipated life expectancy of <12 months
• Those that have legal guardians (due to special permission to enroll in trials)
• Participants with complex chronic conditions per the Pediatric Medical Complexity Algorithm (e.g., trisomy 21)
• Patients with contraindications to non-steroidal anti-inflammatory drug (NSAID) drugs in the NSAID arm, opioid drugs in the opioid arm, or acetaminophen will be excluded.
• Liver disease
• Acute psychiatric instability (defined as current uncontrolled severe depression, severe post-traumatic stress disorder (PTSD), or suicidal ideation), substance use disorder not in remission or treatment, and history of diversion of controlled substances (opioids)

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: Acetaminophen/NSAID regimen	Drug: NSAID; Once randomized to this group the surgical team will elect to prescribe 1 of the following treatment options for post-discharge pain: Ibuprofen 10 milligrams(mg)/kilogram (kg) (maximum 600mg) by mouth every 6 hours around the clock for 2 days, then as needed for pain thereafter (40 doses); Celecoxib 6mg/kg (maximum 400mg) by mouth once then 3 mg/kg (maximum 200mg) every 12 hours around the clock for 2 days, then as needed for pain thereafter (40 doses); Other Names: Ibuprofen; Celecoxib; Drug: Acetaminophen; Participants will receive 15mg/kg up to 1000mg by mouth every 6 hours around the clock for the first 2 days after discharge from surgery then as needed thereafter (40 doses)
Other: Acetaminophen/NSAID/Opioid regimen	Drug: Acetaminophen; Participants will receive 15mg/kg up to 1000mg by mouth every 6 hours around the clock for the first 2 days after discharge from surgery then as needed thereafter (40 doses); Drug: Opioid; Once randomized to this group the surgical team will elect to prescribe for 1 of the following treatment options to be given post procedure for post-discharge pain: Oxycodone 0.1 mg/kg (maximum 5 mg) by mouth every 4 to 6 hours as needed for pain, number 10 doses.; Hydromorphone 0.04 mg/kg (maximum mg) by mouth 4 to 6 hours as needed, number 10 doses; Other Names: Oxycodone; Hydromorphone; Drug: Ibuprofen; Ibuprofen 10mg/kg (maximum 600 mg) by mouth every 6 hours around the clock for 2 days after discharge from surgery then as needed thereafter (40 doses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness outcome - Pain intensity based on Brief Pain Inventory (BPI) pain intensity score at the surgical site over 14 days post-surgery	This is a one question survey in which the worst pain intensity recorded (0-10 being the worst) will be used.	14 days post-surgery, and up to 12 months after surgery
Safety outcome - number and severity of any adverse medication-related symptoms over 14 days post-surgery	Symptom Checklist will proactively screen patients for reports of adverse events from analgesic medications over the first 14 days post-surgery.	14 days post-surgery, and 1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Outcomes Measurement Information System (PROMIS) Pediatric Sleep Disturbance v1.0 short form 4a	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).	Baseline and 1 month after surgery
Patient Global Impression of Change (PGIC)	The perception of improvement or worsening after treatment will be assessed by the patient global impression of change PGIC (range 0-7).	Day 7 up to 12 months after surgery
PROMIS Pediatric Pain Interference scale (Short form-8a)	This is an 8-question survey in which participants will rate statements pertaining to how pain interferes with activities and function.	Baseline up to 12 months after surgery
Pain Catastrophizing Scale (PCS)	This is a 6-question survey in which participants will rate statements pertaining to their experience of pain.	Baseline up to 12 months after surgery
Pediatric Quality of Life Inventory Short Form 15	There are 15 questions with four scales for function related to physical, emotional, social, and school dimensions for adolescents. Participants answer questions from never (0) to almost always (4).	Baseline up to 12 months 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.	Day 3, 1 week, and 2 weeks after surgery
Patient Health Questionnaire (PHQ-2)	There are 2 questions that are completed to screen for depression. Participants answer from not at all (0) to Nearly every day (3). The scores range from 0-6 with a higher score indicating higher levels of depression.	Baseline up to 12 months after surgery
Generalized Anxiety Disorder (GAD-2)	There are 2 questions that are completed to screen for anxiety. Participants answer from not at all (0) to Nearly every day (3). The scores range from 0-6 with a higher score indicating higher levels of anxiety.	Baseline up to 12 months after surgery
Brief Screening Instrument for Adolescent Tobacco, Alcohol, and Drug Use	This is a 6-question survey about the participants' use of tobacco, alcohol and drugs.	Baseline up to 12 months after surgery
National Survey on Drug Use and Health Questions on Opioid Misuse	This is a one question survey that assesses opioid misuse defined as use that is more than prescribed, for non pain-related reasons, or in a way not prescribed by a doctor.	Baseline up to 12 months after surgery
New prolonged opioid use	One question that will assess opioid prescription fills to identify new prolonged opioid use after surgery	Up to 12 months after surgery
Acute pain based on The Michigan Body Map	Participants will document/mark on this image map to identify areas in which acute pain was felt.	Up to 12 months after 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.	Up to 12 months after surgery
Chronic pain based on Brief Pain Inventory (BPI) pain intensity score up to 12 months after surgery	One question survey in which the participants rate pain intensity recorded (0-10), ten being the worst.	to 12 months after surgery
Healthcare Utilization related to pain	Participants will answer questions about their healthcare utilization related to pain 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.	Up to 12 months after surgery
Analgesic medication use	Participants will answer questions about their analgesic medication use for acetaminophen, NSAIDs, opioids, and other medications, including prescription fills, over-the-counter use, and consumption. The study team will also review health record for prescription fills.	Up to 12 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

Publications and helpful links

Helpful Links

• Project Summary on pcori.org

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2025
• Primary Completion (Estimated): October 16, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Acetaminophen; Opioids; NSAIDS; Gallbladder removal; Medications after surgery; Analgesics, opioid; Analgesics, non-narcotic; Tonsil removal; Knee scope
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Physiological Effects of Drugs; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Antirheumatic Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Narcotics; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Benzene Derivatives; Heterocyclic Compounds, 4 or More Rings; Acids, Carbocyclic; Benzenesulfonamides; Sulfonamides; Sulfones; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Central Nervous System Agents; Morphine Derivatives; Pyrazoles; Codeine; Phenylpropionates; Celecoxib; Acetaminophen; Analgesics, Opioid; Hydromorphone; Ibuprofen; Oxycodone; Anti-Inflammatory Agents, Non-Steroidal
• Other Study ID Numbers: HUM00252793; BPS-2023C1-32147 (Other Grant/Funding Number: Patient-Centered Outcomes Research Institute (PCORI))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: Anticipated summer 2029 with no end date
• IPD Sharing Access Criteria: Investigators can access the IPD and supporting information for analyses related to aims in the proposal. The proposed used of the data needs to be approved by a review committee and the sponsor. Proposals may be submitted up to 36 months after data availability, after which data will be available in a data warehouse but without investigator support.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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