Non-Opioid Pain Medications for Children on Mechanical Ventilation

(OPTICOM Trial)

Recruiting at 15 trial locations

Overseen By Kammy Jacobsen

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Weill Medical College of Cornell University

Must be taking: Opioids

Must not be taking: Lithium, Pentoxifylline, Probenecid

Disqualifiers: Allergies, Peptic ulcers, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

644 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether non-opioid medications, such as acetaminophen (Tylenol) and ketorolac (Toradol), can manage pain for children on ventilators with acute respiratory failure. Doctors currently use opioids, but these may not be the best option since many children still experience pain. Researchers will divide participants into groups to receive either the non-opioid medications or a placebo, and they will compare the effects. Children on a ventilator due to breathing problems and who are already receiving or will receive opioid pain relief might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking pain management solutions for children.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you need to take certain medications like lithium, pentoxifylline, or probenecid. It's best to discuss your current medications with the trial team to see if they affect your eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that intravenous acetaminophen (IV Tylenol) reduced the time patients needed IV opioids by 15.5%. Although the FDA has not approved IV acetaminophen for children under 2, it is still used in this age group, and recent research shows no major safety concerns, indicating it is generally safe for children.

For intravenous ketorolac (IV Toradol), research shows it is safe for short-term use in children over 1 year old. Studies suggest that a lower dose of ketorolac can reduce the risk of kidney problems and bleeding, common concerns with this medication.

Overall, current research considers both acetaminophen and ketorolac safe when used at the correct dose. This provides a strong basis for studying their potential to reduce pain in children on ventilators without heavily relying on opioids. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for children on mechanical ventilation because they offer non-opioid options for pain management, which is crucial given the risks associated with opioids. Unlike opioid-based treatments, intravenous acetaminophen and ketorolac work through different mechanisms—acetaminophen mainly reduces fever and pain, while ketorolac is a powerful anti-inflammatory. These treatments are administered intravenously, providing fast and effective pain relief, which is particularly beneficial for children who cannot take medications orally. By potentially reducing opioid use, these treatments can lessen the side effects and dependency risks associated with traditional pain management in critically ill children.

What evidence suggests that this trial's treatments could be effective for managing pain in children on mechanical ventilation?

Research has shown that administering acetaminophen through an IV can reduce opioid use by 15.5% when given beforehand. This approach may improve pain management for children on ventilators without relying solely on strong painkillers. In this trial, some participants will receive intravenous acetaminophen. Additionally, ketorolac has proven effective for managing sudden pain in children, with studies showing it significantly reduces pain. It is considered safe and can help control pain in young patients. Other participants in this trial will receive intravenous ketorolac. By combining these non-opioid options, as tested in one of the trial arms, there is hope for better pain management in children with severe breathing problems. ^{1 2 3 5 6}

Who Is on the Research Team?

Chani Traube, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for children with acute respiratory failure who are on mechanical ventilation. It aims to find out if non-opioid pain medications like acetaminophen or ketorolac can better manage their pain compared to opioids, which over 90% of these kids still feel despite strong doses.

Inclusion Criteria

Expected duration of Invasive Mechanical Ventilation > 48 hours

I am between 2 months and 17.5 years old.

I needed a breathing tube for severe breathing problems.

Exclusion Criteria

Requirement for tight temperature control

History of allergic-type reaction to either acetaminophen or non-steroidal anti-inflammatory (NSAID) medications

Platelet count < 100,000/microliter

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

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

5 days

Daily monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• Ketorolac

Trial Overview The study tests the effectiveness of intravenous acetaminophen and ketorolac versus a placebo in managing pain for ventilated children with acute respiratory failure. Participants will be randomly assigned to one of four groups to compare how well each treatment works at reducing the need for opioids.

How Is the Trial Designed?

Group I: Intravenous Ketorolac (IV-K) + Intravenous Placebo Experimental Treatment 2 Interventions

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

Group II: Intravenous Acetaminophen (IV-A) + Intravenous Placebo Experimental Treatment 2 Interventions

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

Group III: Intravenous Acetaminophen (IV-A) + Intravenous Ketorolac (IV-K) Experimental Treatment 2 Interventions

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

Group IV: Intravenous Placebo + Intravenous Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9088446/

National Intravenous Acetaminophen Use in Pediatric ... Intravenous acetaminophen prescription was associated with a 54.8% increase in opioid duration when compared with patients who received opioids ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2787283

Association of Intravenous Acetaminophen Administration ... In this comparative effectiveness study, IV acetaminophen administered prior to IV opioids was associated with a reduction in IV opioid duration by 15.5%.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06994442

Optimizing Pain Treatment in Children On Mechanical ... In this clinical trial, investigators want to learn more about using non-opioid pain medications for children with acute respiratory failure.

4. publications.aap.org publications.aap.org/hospitalpediatrics/article/11/7/734/179864/Variation-in-Intravenous-Acetaminophen-Use-in

Variation in Intravenous Acetaminophen Use in Pediatric ... Among 866 346 encounters, 14.4% received 1 dose of IV acetaminophen with 287 935 DOT, costing $29.8 million. In multivariable analysis age, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6213625/

Use of Intravenous Acetaminophen in Children for Analgesia ... The aim of this study was to determine if intravenous (IV) acetaminophen would reduce opioid requirements and improve clinical outcomes in children after ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/pediatric/22450_Acetaminophen_Clinical_Safety_PREA.pdf

22450_Acetaminophen_Clinical... Adults and adolescents weighing 50 kg and over: 650 to. 1000 mg every 4-6 hours. Adults and adolescents weighing under 50 kg and all.