What side effects are associated with this type of intervention?

The most common treatments for Patent Ductus Arteriosus (PDA) involve the use of NSAIDs such as ibuprofen. Known side effects of ibuprofen in this context include potential gastrointestinal bleeding and renal impairment. However, in studies, these adverse effects were not observed in the treatment groups. Additionally, NSAIDs can have harmful effects on the gut and kidneys of extremely preterm infants, which raises concerns about their use in this vulnerable population.

What prior FDA approvals exist?

The FDA has approved the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and ibuprofen for the treatment of Patent Ductus Arteriosus (PDA) in preterm infants. These drugs work by inhibiting the cyclooxygenase (COX) enzyme, which reduces the production of prostaglandins that keep the ductus arteriosus open. By lowering prostaglandin levels, these medications help to close the PDA. Both indomethacin and ibuprofen have been widely studied and are commonly used in clinical practice for this purpose.

What other types of research exist?

Promising novel alternatives to early medical treatment with NSAIDs for Patent Ductus Arteriosus (PDA) patients include the use of paracetamol (acetaminophen), which has shown efficacy in closing PDA with potentially fewer side effects. Additionally, advancements in catheter-based interventions, such as transcatheter PDA closure, offer a non-pharmacological option that can be performed even in very low birth weight infants. Ongoing research into the genetic and molecular pathways involved in PDA may also lead to the development of targeted therapies that could provide more effective and safer treatment options in the future.

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Nonsteroidal Anti-inflammatory Drug

Ibuprofen for Patent Ductus Arteriosus (SMART-PDA Trial)

Phase 3

Recruiting

Led By Souvik Mitra, MD, MSc

Research Sponsored by IWK Health Centre

Eligibility Criteria Checklist

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

Must have

Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation

Be younger than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up birth through 36 weeks post menstrual age

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial aims to determine if early treatment of a common heart condition in extremely preterm infants is beneficial. The treatment involves using medications like ibuprofen to help close the heart condition. Ibuprofen has recently been shown to be effective with fewer side effects compared to other medications. The study will compare early treatment to no early treatment to see which approach is better.

Who is the study for?

This trial is for preterm infants born before completing 26 weeks of gestation and diagnosed with Patent Ductus Arteriosus (PDA). Infants without PDA, those with significant congenital heart disease or other major anomalies, or if there's a decision to withhold care are excluded.

What is being tested?

The study tests whether giving Ibuprofen early on to extremely premature babies with PDA is beneficial compared to no treatment. Babies will be randomly assigned to either receive the drug early or not in their first week of life.

What are the potential side effects?

Ibuprofen may cause side effects such as potential harm to the gut and kidneys in these very young patients. The exact side effects will be closely monitored due to the vulnerability of this age group.

Eligibility Criteria

Inclusion Criteria

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

Select...

My baby was born before completing 26 weeks of pregnancy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ birth through 36 weeks post menstrual age

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~birth through 36 weeks post menstrual age

This trial's timeline: 3 weeks for screening, Varies for treatment, and birth through 36 weeks post menstrual age for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Chronic lung disease

Completeness of data collection for clinical outcomes

Definite sepsis

+9 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Selective early medical treatment (SMART) strategyExperimental Treatment1 Intervention

Infants who are randomized to experimental group will follow the SMART treatment protocol, which includes echocardiographic screening every 72 hours to categorize PDA disease severity by combining clinical and echocardiographic features. At any evaluation if patients are found to have a "severe PDA" on echocardiography, irrespective of clinical symptoms, or a "moderate PDA" on echocardiography with at least moderate clinical illness, they will receive pharmacotherapy aimed at PDA closure (The PDA severity has been divided into mild, moderate or severe based on pre-defined clinical and echocardiographic criteria).

Group II: Early conservative management strategyActive Control1 Intervention

Infants randomized to this arm will not undergo any further echocardiographic assessment or pharmacological treatment of the PDA regardless of the clinical signs. If the infant gets an echocardiographic assessment for a reason different than PDA assessment (such as hypotension or oxygenation failure) and a PDA is incidentally noted that fits the treatment criteria, the infant will not be initiated on pharmacotherapy. After 7 days of age, decision on PDA assessment and treatment will be at the discretion of the treating physician.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibuprofen

2013

Completed Phase 4

~5800

0 / 1Eligibility 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

The most common treatments for Patent Ductus Arteriosus (PDA) involve the use of NSAIDs like ibuprofen and indomethacin. These medications inhibit the enzyme cyclooxygenase (COX), which is essential for the production of prostaglandins. Prostaglandins help keep the ductus arteriosus open in the fetal circulation. By reducing prostaglandin levels, NSAIDs facilitate the closure of the ductus arteriosus after birth. This is crucial for PDA patients because a persistent PDA can lead to serious complications such as heart failure and respiratory problems. Early treatment with NSAIDs helps prevent these issues by promoting the natural closure of the ductus arteriosus, thereby improving outcomes for preterm infants.