Recruiting

Phase 3

Acetaminophen & KetorolacOptimizing Pain Treatment in Children On Mechanical Ventilation

Sponsor:

Weill Medical College of Cornell University

Code:

NCT06994442

Conditions

Mechanical Ventilation

Pediatric Acute Respiratory Failure

Analgesics, Opioid

Sedation and Analgesia

Eligibility Criteria

Sex: All

Age: 0 - 17

Healthy Volunteers: Not accepted

Interventions

Acetaminophen

Ketorolac

Placebo

Study Details

Brief summary:

In this clinical trial, investigators want to learn more about using non-opioid pain medications for children with acute respiratory failure. Right now, doctors give these children opioids to help with pain while they are on the ventilator, but investigators don't know if this is the best way to manage their pain. Even with strong doses of opioids, more than 90% of these children still feel pain. Other pain medicines, like acetaminophen (also called Tylenol) and ketorolac (also called Toradol), are available but aren't commonly used because we don't know if they help. The goal of this clinical trial is to test if acetaminophen and/or ketorolac can improve pain control and reduce the need for stronger pain medications (opioids) in these children.

To learn more about this, participants will be randomly placed in one of four study treatment groups. This means that a computer will decide by chance which group each participant is in, not the doctors running the study. Each group will receive a combination of intravenous acetaminophen, ketorolac or a harmless substance called a placebo. In this clinical trial, placebos help investigators see if the actual medications (acetaminophen and ketorolac) work better than something that doesn't contain medicine. By comparing participants who get the real medicine with those who get the placebo, investigators can find out if these medications effectively decrease pain.

Conditions

Mechanical Ventilation

Pediatric Acute Respiratory Failure

Analgesics, Opioid

Sedation and Analgesia

Study ID

NCT06994442

Start date

Dec 29, 2025

Status verified date

Jul, 2026

Completion date

Aug 31, 2029

Anticipated

Primary completion date

Jul 31, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 17

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. At least 2 months of age to 17 years 6 months; AND
2. Acute Respiratory Failure requiring endotracheal intubation; AND
3. Opioid infusion planned or started; AND
4. Expected duration of Invasive Mechanical Ventilation > 48 hours

Exclusion Criteria:

1. History of allergic-type reaction to either acetaminophen or non-steroidal anti-inflammatory (NSAID) medications; OR
2. Active peptic ulcer disease, recent gastrointestinal bleeding or perforation, or history of peptic ulcer disease or gastrointestinal bleeding; OR
3. Expected need for continuous neuromuscular blockade for more than 24 hours following intubation; OR
4. Requirement for tight temperature control (defined as the requirement for continuous administration of antipyretic medications to prevent secondary injuries associated with fever); OR
5. Platelet count < 100,000/microliter; OR
6. Known liver disease (defined as pre-existing diagnosis of hepatic insufficiency, or a serum ALT > 5 times upper limit of normal or serum total bilirubin > 2 times the upper limit of normal, as defined by hospital laboratory standards); OR
7. Known kidney disease (defined as pre-existing diagnosis of renal insufficiency, or an estimated creatinine clearance < 30 mL/min/m2 obtained within the previous 24-hours prior to eligibility, or high risk of renal failure due to volume depletion); OR
8. Current treatment with extracorporeal therapies (e.g., ECMO, CVVH, plasma exchange); OR
9. Cardiac bypass surgery within the past 24 hours prior to eligibility; OR
10. Requirement for the patient to receive lithium, pentoxifylline or probenecid as part of their routine care; OR
11. Unable to obtain consent and randomize within 12 hours of eligibility, OR
12. Positive pregnancy test; OR
13. Coma, Vegetative State, or Brain Death (Pediatric Cerebral Performance Category (PCPC) score of 5 or 6) suspected or confirmed; OR
14. Cardiac arrest has occurred within 72 hours of eligibility criteria being met; OR
15. Limitations in care in place at the time of eligibility, or anticipated to be considered during the 5-day study period, OR
16. Use of high dose NSAIDS within the prior 6 months, OR
17. Suspected or confirmed cerebrovascular bleeding or hemorrhagic diathesis

Study Design

Enrollment

644 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Intravenous Acetaminophen (IV-A) + Intravenous Placebo

Participants receive intravenous acetaminophen and intravenous placebo every 6 hours, alongside open-label opioids per standard of care, for up to 5 days.

experimental: Intravenous Ketorolac (IV-K) + Intravenous Placebo

Participants receive intravenous ketorolac and intravenous placebo every 6 hours, alongside open-label opioids per standard of care, for up to 5 days.

experimental: Intravenous Acetaminophen (IV-A) + Intravenous Ketorolac (IV-K)

Participants receive intravenous acetaminophen and intravenous ketorolac every 6 hours, alongside open-label opioids per standard of care, for up to 5 days.

placebo comparator: Intravenous Placebo + Intravenous Placebo

Participants receive intravenous placebo infusions every 6 hours, alongside open-label opioids per standard of care, for up to 5 days.

Interventions

Acetaminophen

Intravenous (IV) dose, 15 mg/kg\* (maximum 1g) every 6 h for 5 days.

\*Note: The dosing of acetaminophen for intravenous infusion will follow the current Acetaminophen for injection labeling based on the participant's age and weight.

Ketorolac

IV dose; 0.5mg/kg (maximum 15 mg) every 6 h for 5 days.

\*Note: Ketorolac for intravenous bolus administration is currently labeled for multiple-dose treatment in adults. For patients under 65 years of age, the recommended dose is 30 mg every 6 hours, with a maximum daily dose of 120 mg. For patients 65 years or older, renally impaired patients, and those weighting less than 50 kg, the recommended dose is 15 mg every 6 hours, with a maximum daily dose of 60 mg. In this study, we will be limiting ketorolac to ≤15 mg per dose, with a maximum of 60 mg per day.

Placebo

Placebos will be normal saline solution, i.e., 0.9% NaCl. In order to maintain blinding, the investigational pharmacy will dispense placebo in a volume to match the corresponding study drug.

Primary outcome measure

Acute Pain Episodes [ Time Frame: First 5 days of mechanical ventilation or until extubation, whichever comes first ]

Central Contacts and Locations

Central contacts

Chani Traube, MD

212-746-3056 chr9008@med.cornell.edu

Kammy Jacobsen

kammy.jacobsen@hsc.utah.edu

Locations

Arkansas Children's Hospital

Recruiting

Little Rock, Arkansas, United States, 72202

Contacts

Ronald Sanders, MD

501-364-4166 rcsanders@uams.edu

Children's National Hospital

Recruiting

Washington D.C., District of Columbia, United States, 20010-2916

Contacts

Sonali Basu, MD

202-476-5923 sbasu@childrensnational.org

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109-1274

Contacts

Erin Carlton, MD

734-764-5302 ecarlton@umich.edu

Children's Hospital of Michigan

Recruiting

Detroit, Michigan, United States, 48201-2119

Contacts

Kathleen Meert, MD

313-745-5891 meert1kl@cmich.edu

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55454-1450

Contacts

Joseph Resch, MD

612-625-6678 resch066@umn.edu

Duke Children's Hospital & Health Center

Recruiting

Durham, North Carolina, United States, 27705-4677

Contacts

Christoph Hornik, MD

919-668-2773 christoph.hornik@duke.edu

Rainbow Babies and Children's Hospital

Recruiting

Cleveland, Ohio, United States, 44106-4919

Contacts

Joseph Kohne, MD

888-412-2454 Joseph.Kohne@uhhospitals.org

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205-2664

Contacts

Ambrish Patel, MD

614-722-4206 ambrish.patel@nationwidechildrens.org

Penn State Health/Hershey Medical Center

Recruiting

Hershey, Pennsylvania, United States, 17033-0850

Contacts

Neal Thomas, MD

717-531-5337 nthomas@pennstatehealth.psu.edu

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4319

Contacts

Heather Wolfe, MD

614-440-2116 WolfeH@chop.edu

University of Pittsburgh

Recruiting

Pittsburgh, Pennsylvania, United States, 15261-0001

Contacts

Ericka Fink, MD

412-692-6076 finkel@ccm.upmc.edu

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

John Costello, MD

843-792-8129 costello@musc.edu

Primary Children's Medical Center

Recruiting

Salt Lake City, Utah, United States, 84112-9023

Contacts

Jill Sweney, MD

801-587-7572 jill.sweney@hsc.utah.edu

Wisconsin Children's

Recruiting

Milwaukee, Wisconsin, United States, 53226-3548

Contacts

Nathan Thompson, MD

414-266-3360 nathomps@mcw.edu

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Jul 30, 2026

Last verified

Jul, 2026

Keywords

Acetaminophen
Ketorolac
Non-opioids
Acute Respiratory Failure in Children
Mechanically Ventilated Children in the ICU
Pediatric Delirium
Pain Treatment
opioids
sedation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2026-07-30.