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.
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
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
Factorial
Acetaminophen
DrugIntravenous (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
DrugIV 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
DrugPlacebos 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.
Acute Pain Episodes
Pain will be assessed using the Face, Legs, Activity, Cry, Consolability (FLACC) score. Coma will be defined using standardized sedation scales. The number of time periods where the participant is both pain-free (FLACC \<4) and coma-free will be recorded.
Opioid Exposure
Opioid exposure will be quantified in morphine milligram equivalents per kilogram during the first 5 days of mechanical ventilation.
Benzodiazepine Exposure
Total benzodiazepine exposure (in midazolam milligram equivalents per kilogram) during the first 5 days of mechanical ventilation.
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Weill Medical College of Cornell University
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
