Ibuprofen for Patent Ductus Arteriosus

(MIPD-PDA Trial)

Overseen By Samira Samiee-Zafarghandy, MD, FRCPC

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Hamilton Health Sciences Corporation

Must be taking: Ibuprofen

Disqualifiers: Congenital abnormalities, Hepatic failure, Sepsis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 4 days

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to use ibuprofen to treat patent ductus arteriosus (PDA) in premature newborns. PDA is a serious heart issue that can lead to dangerous complications if untreated. The study compares two methods: administering a standard dose of ibuprofen or adjusting the dose based on each baby's needs. This trial involves very small newborns in the NICU diagnosed with PDA, with parental consent for participation. The primary goal is to determine if a larger study can be successfully conducted in the future. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, contributing to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Previous studies have used ibuprofen to help close a condition called patent ductus arteriosus (PDA) in newborns. Research has shown that ibuprofen is generally well-tolerated for this purpose, especially compared to indomethacin. For example, one study found that ibuprofen posed a lower risk of causing necrotizing enterocolitis (NEC), a serious gut problem, compared to indomethacin.

Regarding dosage, one study indicated that precision dosing of ibuprofen aims to personalize the amount given to each baby, potentially avoiding doses that exceed safety limits. The standard method involves administering a fixed amount based on the baby's age, which has been used safely for some time.

Overall, ibuprofen is considered safe for use in newborns with PDA, particularly when doctors carefully monitor the dose. This ongoing study will compare the usual method of administering ibuprofen with a new approach that adjusts the dose based on the drug's concentration in the baby's blood, potentially enhancing treatment safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ibuprofen for Patent Ductus Arteriosus (PDA) because it offers a more refined dosing approach compared to traditional treatments like indomethacin or surgical options. The precision dosing method in this study uses a state-of-the-art Web-Accessible Population Pharmacokinetics Service (WAPPS-PDA) to tailor the ibuprofen regimen, potentially optimizing effectiveness and safety for each patient. This personalized approach could lead to more efficient closure of the ductus arteriosus with fewer side effects, making treatment safer and more effective for newborns.

What evidence suggests that this trial's ibuprofen dosing methods could be effective for closing PDA in newborns?

Studies have shown that ibuprofen can help close a condition called patent ductus arteriosus (PDA) in newborns. Research suggests that ibuprofen is as effective as indomethacin for treating this condition. However, the usual method of administering ibuprofen works for only about half of the small newborns. In this trial, participants will join one of two treatment arms. The "Standard Dosing" arm uses a PNA-based standard dosing regimen. The "Precision Dosing" arm explores a new method to adjust doses based on the amount of ibuprofen in the blood, aiming to improve the success rate. When the right amount of ibuprofen enters the baby's body, it can successfully close the PDA. ^{1 3 5 6 7}

Who Is on the Research Team?

Samira Samiee-Zafarghandy, MD, FRCPC

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for newborns who were born prematurely and are diagnosed with patent ductus arteriosus (PDA), a heart condition that can lead to serious health issues. The study aims to find the right ibuprofen dosage for each baby to help close PDA.

Inclusion Criteria

My baby was born at or before 27 weeks and 6 days of pregnancy.

Admitted to the neonatal intensive care unit (NICU) at McMaster Children's Hospital (MCH)

Obtained parental consent

Exclusion Criteria

I have a major congenital or genetic abnormality.

My liver and kidney function tests are within normal limits.

I cannot take oral ibuprofen due to severe health issues like severe jaundice, feeding problems, intestinal damage, bleeding, or very low platelet count.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive either standard or precision dosing of ibuprofen for PDA treatment

4 days

Daily monitoring and dosing adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 days

Regular monitoring for adverse events and PDA closure

Extension

Participants may require additional pharmacotherapy or surgical intervention if PDA remains open

Up to 14 days

What Are the Treatments Tested in This Trial?

Interventions

• Ibuprofen

Trial Overview The trial tests two methods of administering ibuprofen: a standard dose given to all, versus precision dosing tailored based on how much active drug reaches the newborn's blood and their response in closing PDA. It will evaluate feasibility for larger studies and compare effectiveness and safety.

How Is the Trial Designed?

Group I: Precision Dosing Experimental Treatment 1 Intervention

PNA-based regimen only for the initial dose, the rest of regimen will be guided by a MIPD, using a Web-Accessible Population Pharmacokinetics Service (WAPPS-PDA).

Group II: Standard Dosing Active Control 1 Intervention

PNA-based standard dosing of ibuprofen \[ \<= 72 hours PNA: 10/5/5 q24hrs vs \>72 hours PNA 20/10/10 q24hrs\].

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Hamilton Academic Health Sciences Organization

Collaborator

Trials

22

Recruited

5,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07143201

Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT This clinical trial is a single-center, pilot, randomized, controlled, triple-blind study designed to evaluate the feasibility and effectiveness of model- ...

2. trialx.com trialx.com/clinical-trials/listings/315729/precision-dosing-of-oral-ibuprofen-for-pda-a-pilot-rct/

Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT Study Design Overview: This clinical trial is a single-center, pilot, randomized, controlled, triple-blind study designed to evaluate the feasibility and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32045960/

Ibuprofen for the treatment of patent ductus arteriosus in ... Ibuprofen is as effective as indomethacin in closing a PDA. Ibuprofen reduces the risk of NEC and transient renal insufficiency.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2207418

Expectant Management or Early Ibuprofen for Patent ... Although most centers used an initial intravenous ibuprofen dose of 10 mg per kilogram, followed by 5 mg per kilogram at 24 and at 48 hours after the first dose ...

5. publications.aap.org publications.aap.org/pediatrics/article/155/5/e2025071425/201674/Patent-Ductus-Arteriosus-in-Preterm-Infants

Patent Ductus Arteriosus in Preterm Infants | Pediatrics Ibuprofen used intravenously at the standard dose of 10 mg/kg followed by 2 doses of 5 mg/kg at 24-hour intervals may be preferred as it is as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6513618/

Ibuprofen for the treatment of patent ductus arteriosus in ... The risk of NEC was reduced with oral ibuprofen compared with indomethacin (IV or oral) (7 studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical ...

7. trial.medpath.com trial.medpath.com/clinical-trial/9e4f32014c446986/nct07143201-oral-ibuprofen-persistent-patent-ductus-arteriosus

Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT This outcome will evaluate the proportion of participants in the intervention arm whose daily ibuprofen dose does not exceed 40 mg/kg. The ...