RecruitingPhase 3NCT06994442

Optimizing Pain Treatment in Children On Mechanical Ventilation


Sponsor

Weill Medical College of Cornell University

Enrollment

644 participants

Start Date

Dec 29, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 2 MonthsMax Age: 17 Years

Inclusion Criteria4

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

Exclusion Criteria17

  • History of allergic-type reaction to either acetaminophen or non-steroidal anti-inflammatory (NSAID) medications; OR
  • Active peptic ulcer disease, recent gastrointestinal bleeding or perforation, or history of peptic ulcer disease or gastrointestinal bleeding; OR
  • Expected need for continuous neuromuscular blockade for more than 24 hours following intubation; OR
  • Requirement for tight temperature control (defined as the requirement for continuous administration of antipyretic medications to prevent secondary injuries associated with fever); OR
  • Platelet count \< 100,000/microliter; OR
  • 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
  • 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
  • Current treatment with extracorporeal therapies (e.g., ECMO, CVVH, plasma exchange); OR
  • Cardiac bypass surgery within the past 24 hours prior to eligibility; OR
  • Requirement for the patient to receive lithium, pentoxifylline or probenecid as part of their routine care; OR
  • Unable to obtain consent and randomize within 12 hours of eligibility, OR
  • Positive pregnancy test; OR
  • Coma, Vegetative State, or Brain Death (Pediatric Cerebral Performance Category (PCPC) score of 5 or 6) suspected or confirmed; OR
  • Cardiac arrest has occurred within 72 hours of eligibility criteria being met; OR
  • Limitations in care in place at the time of eligibility, or anticipated to be considered during the 5-day study period, OR
  • Use of high dose NSAIDS within the prior 6 months, OR
  • Suspected or confirmed cerebrovascular bleeding or hemorrhagic diathesis

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Interventions

DRUGAcetaminophen

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.

DRUGKetorolac

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.

DRUGPlacebo

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.


Locations(15)

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's National Hospital

Washington D.C., District of Columbia, United States

University of Michigan

Ann Arbor, Michigan, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Duke Children's Hospital & Health Center

Durham, North Carolina, United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Penn State Health/Hershey Medical Center

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Texas Children's Hospital/Baylor College of Medicine

Houston, Texas, United States

Primary Children's Medical Center

Salt Lake City, Utah, United States

Wisconsin Children's

Milwaukee, Wisconsin, United States

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