What side effects are associated with this type of intervention?

The most common treatments for Patent Ductus Arteriosus (PDA) include ibuprofen and acetaminophen. Ibuprofen can cause gastrointestinal issues, renal impairment, and increased risk of bleeding. Acetaminophen, generally safe at therapeutic doses, can lead to liver toxicity if overdosed. Combination therapy of ibuprofen and acetaminophen aims to enhance efficacy by leveraging their different mechanisms of action, but it requires careful monitoring for potential additive side effects.

What prior FDA approvals exist?

The FDA has approved the use of ibuprofen for the treatment of Patent Ductus Arteriosus (PDA) in premature infants. Ibuprofen works by reducing prostaglandin synthesis, which helps close the ductus arteriosus. Acetaminophen, although not specifically FDA-approved for PDA, has also been used off-label for this purpose due to its similar mechanism of reducing prostaglandin synthesis through a different receptor site. The combination therapy of ibuprofen and intravenous acetaminophen is currently being studied for its potential synergistic effects in improving treatment outcomes for PDA.

What other types of research exist?

Promising novel alternatives to the combination therapy of ibuprofen and IV acetaminophen for PDA treatment in 2024 include: 1) Paracetamol (oral or IV) monotherapy, which has shown efficacy in some studies as a safer alternative to NSAIDs. 2) Selective COX-2 inhibitors, which may offer targeted prostaglandin synthesis reduction with potentially fewer side effects. 3) Emerging biologic agents targeting specific pathways involved in ductal closure, though these are still under investigation and not yet widely adopted.

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Nonsteroidal Anti-inflammatory Drug (NSAID)

Acetaminophen + Ibuprofen for Patent Ductus Arteriosus

Phase 2

Recruiting

Led By Amish Jain, MD PhD

Research Sponsored by Mount Sinai Hospital, Canada

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Preterm infants born <27+0 weeks gestational age

Be younger than 18 years old

Must not have

Pre-treatment renal dysfunction defined as urine output < 1ml/kg/hour for the previous 24 hours or serum creatinine > 100 micromol/L

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6-10 days post treatment initiation

Summary

This trial is testing a new combination of ibuprofen and IV acetaminophen to treat a heart problem in very premature babies. These babies often don't respond well to just one drug, so using two drugs together might work better. The goal is to see if this combination is safer and more effective than using ibuprofen alone. Ibuprofen is commonly used to close the ductus arteriosus in premature newborns, and IV acetaminophen has shown effectiveness in similar treatments.

Who is the study for?

This trial is for extremely premature infants (born before 27 weeks) with a heart condition called PDA, where the duct fails to close after birth. Infants must not have had previous PDA treatment, except for indomethacin used to prevent bleeding in the brain. They should also have normal kidney and liver function and an adequate platelet count.

What is being tested?

The study tests if giving Ibuprofen together with IV Acetaminophen is more effective than Ibuprofen alone for treating PDA in very early-born babies. The goal is to see if this combination can improve outcomes by acting on different pathways that keep the duct open.

What are the potential side effects?

Possible side effects include issues related to liver or kidney function, blood clotting problems due to low platelets, gastrointestinal disturbances like stomach pain or nausea, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My baby was born before 27 weeks of pregnancy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My kidneys are not working well, shown by low urine output or high creatinine.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6-10 days post treatment initiation

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6-10 days post treatment initiation

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6-10 days post treatment initiation for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Composite of pre-discharge mortality or any grade BPD

Secondary study objectives

Duration (days) of invasive or non-invasive respiratory support

Further exposure to pharmacological PDA treatments

Mortality

+8 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Combination TherapyExperimental Treatment2 Interventions

Intravenous or enteral ibuprofen, as decided by clinical team, in the standard clinical dose used in participating NICUs (typically, for neonates \< 7 days old - 10 mg/kg/dose on day 1, 5 mg/kg/dose q24h on days 2 and 3; for neonates \> 7 days old - 20 mg/kg/dose on day 1, 10 mg/kg/dose q24h on days 2 and 3) And study drug (intravenous acetaminophen 15 mg/kg/dose IV q6h for 3 days).

Group II: Standard Clinical Practice - MonotherapyPlacebo Group2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Acetaminophen Injection

2023

N/A

~70

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Patent Ductus Arteriosus (PDA) is commonly treated with medications that reduce prostaglandin synthesis, as prostaglandins are responsible for keeping the ductus arteriosus open. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), inhibits the cyclooxygenase (COX) enzymes, thereby reducing prostaglandin production. Acetaminophen, although primarily known for its analgesic and antipyretic effects, also reduces prostaglandin synthesis through a different receptor site. The combination therapy of ibuprofen and intravenous acetaminophen leverages their synergistic effects to more effectively decrease prostaglandin levels, promoting the closure of the ductus arteriosus. This is crucial for PDA patients, especially extremely premature infants, as successful early treatment can significantly reduce the risk of complications such as bronchopulmonary dysplasia and improve overall survival rates.

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