Optimizing Pain Treatment in Children On Mechanical Ventilation

NCT ID: NCT06994442

Last Updated: 2026-02-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 644 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-29
• Study Completion Date: 2029-08-31

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.

Detailed Description

The OPTICOM (Optimizing Pain Treatment In Children On Mechanical Ventilation) study is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to improve pain management and reduce opioid exposure in critically ill children requiring invasive mechanical ventilation (MV) for acute respiratory failure (ARF).

More than 24,000 children annually in the United States require MV for ARF, yet current analgesic management relies heavily on opioids, often resulting in suboptimal pain control and significant risks including physiological dependence, withdrawal, delirium, and prolonged hospitalization. Despite the high-dose opioid use, over 90% of these children experience inadequate pain relief. There are currently no evidence-based, pediatric-specific guidelines to optimize analgesia in this population.

OPTICOM will evaluate whether the administration of intravenous acetaminophen (IV-A) and/or intravenous ketorolac (IV-K), as non-opioid adjuncts, can reduce pain and opioid exposure in this vulnerable population. A total of approximately 644 participants aged 2 months to 17 years 6 months, requiring MV and opioid infusions, will be randomized in a 1:1:1:1 ratio into one of four treatment arms: (1) IV-A + placebo, (2) IV-K + placebo, (3) IV-A + IV-K, or (4) placebo + placebo. Study drugs will be administered for a maximum of 5 days. Opioid and benzodiazepine use will continue as open-label per local standard of care.

The study employs a factorial design with stratified randomization by site. The analysis plan includes multivariable Poisson regression models to evaluate the independent and combined effects of IV-A and IV-K on primary and secondary outcomes. Sample size calculations provide >90% power to detect meaningful differences in pain control and opioid reduction.

Conditions

Mechanical Ventilation; Pediatric Acute Respiratory Failure; Analgesics, Opioid; Sedation and Analgesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Ketorolac

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chani Traube, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status: RECRUITING

Children's National Hospital

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

Site Status: NOT_YET_RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status: NOT_YET_RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status: RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Duke Children's Hospital & Health Center

Durham, North Carolina, United States

Site Status: RECRUITING

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status: RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status: RECRUITING

Penn State Health/Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status: RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: RECRUITING

Texas Children's Hospital/Baylor College of Medicine

Houston, Texas, United States

Site Status: NOT_YET_RECRUITING

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status: RECRUITING

Wisconsin Children's

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Chani Traube, MD

Role: CONTACT

chr9008@med.cornell.edu

212-746-3056

Kammy Jacobsen

Role: CONTACT

kammy.jacobsen@hsc.utah.edu

Facility Contacts

Ronald Sanders, MD

Role: primary

rcsanders@uams.edu

501-364-4166

Sonali Basu, MD

Role: primary

sbasu@childrensnational.org

202-476-5923

Erin Carlton, MD

Role: primary

ecarlton@umich.edu

734-764-5302

Kathleen Meert, MD

Role: primary

meert1kl@cmich.edu

313-745-5891

Joseph Resch, MD

Role: primary

resch066@umn.edu

612-625-6678

Christoph Hornik, MD

Role: primary

christoph.hornik@duke.edu

919-668-2773

Joseph Kohne, MD

Role: primary

Joseph.Kohne@uhhospitals.org

888-412-2454

Ambrish Patel, MD

Role: primary

ambrish.patel@nationwidechildrens.org

614-722-4206

Neal Thomas, MD

Role: primary

nthomas@pennstatehealth.psu.edu

717-531-5337

Heather Wolfe, MD

Role: primary

WolfeH@chop.edu

614-440-2116

Ericka Fink, MD

Role: primary

finkel@ccm.upmc.edu

412-692-6076

John Costello, MD

Role: primary

costello@musc.edu

843-792-8129

Ayse Arikan, MD

Role: primary

aysea@bcm.edu

832-824-3827

Jill Sweney, MD

Role: primary

jill.sweney@hsc.utah.edu

801-587-7572

Nathan Thompson, MD

Role: primary

nathomps@mcw.edu

414-266-3360

Other Identifiers

U01HD116260

Identifier Type: NIH

Identifier Source: secondary_id

View Link

24-12028276

Identifier Type: -

Identifier Source: org_study_id