Precision dosing of oral ibuprofen to close PDA in very preterm newborns
Model Informed Precision Dosing of Oral Ibuprofen for Treatment of Persistent Patent Ductus Arteriosus: A Pilot Randomized Controlled Feasibility Trial
This study will test whether adjusting oral ibuprofen doses for each very preterm baby using blood levels and echocardiograms helps close a patent ductus arteriosus more often than the standard fixed dose.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 26 (estimated) |
| Ages | N/A to 28 Weeks |
| Sex | All |
| Sponsor | Hamilton Health Sciences Corporation Academic / other |
| Locations | 1 site (Hamilton, Ontario) |
| Trial ID | NCT07143201 on ClinicalTrials.gov |
What this trial studies
This single-center, pilot, randomized, controlled, triple-blind Phase 2 trial compares standard fixed oral ibuprofen dosing to model-informed precision dosing (MIPD) in preterm neonates ≤27+6 weeks with PDA. The MIPD arm uses initial loading doses followed by dose adjustments guided in real time by blood samples taken at 6, 30, and 54 hours and targeted echocardiography interpreted through the WAPPS-PDA Bayesian PK tool. The standard arm receives the same initial regimen but subsequent doses are not altered based on PK or echo results, although samples and echos are collected for comparison. The study focuses on feasibility, achieved drug exposure, and clinical PDA closure outcomes in a small cohort.
Who should consider this trial
Good fit: Very preterm neonates (gestational age ≤27+6 weeks) admitted to the McMaster Children's Hospital NICU with a PDA judged to need treatment and with parental consent.
Not a fit: Infants with major congenital or genetic abnormalities, active uncontrolled sepsis, significant hepatic or renal failure, or contraindications to oral ibuprofen (for example NEC, GI perforation, severe thrombocytopenia, severe feeding intolerance, or hyperbilirubinemia requiring exchange transfusion) are unlikely to benefit and are excluded.
Why it matters
Potential benefit: If successful, personalized dosing could increase the chance of closing the PDA in very preterm infants and reduce complications from a persistent PDA.
How similar studies have performed: Prior work shows that adequate ibuprofen exposure is linked to PDA closure and that neonates have variable ibuprofen pharmacokinetics, but real-time model-informed precision dosing for PDA is relatively novel and not yet validated in larger trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Neonates with a gestational age of ≤27+6 weeks * Admitted to the neonatal intensive care unit (NICU) at McMaster Children's Hospital (MCH) * Diagnosed with PDA in need of treatment based on targeted neonatal echocardiography (TnEcho) performed prior to 27+6 CGA or postnatal age of 3 days, whichever comes later. * Obtained parental consent. Exclusion Criteria: * Major congenital or genetic abnormalities * Evidence for clinical or biochemical hepatic or renal failure (AST \> 225 U/L, ALT \> 150 U/L, or serum creatinine \> 130 µmol/L) * Sepsis - as defined by confirmed uncontrolled/active sepsis which will preclude any treatment of PDA * Contraindications to receive oral ibuprofen: * Severe hyperbilirubinemia in need for exchange transfusion * Severe feeding intolerance * Necrotizing enterocolitis (NEC) * Gastrointestinal perforation * Active bleeding * Severe thrombocytopenia (\< 50× 109/L)
Where this trial is running
Hamilton, Ontario
- McMaster Children's Hospital - Neonatal Intensive Care Unit — Hamilton, Ontario, Canada (Recruiting)
Study contacts
- Principal investigator: Samira Samiee-Zafarghandy, MD, FRCPC — McMaster University
- Study coordinator: Samira Samiee-Zafarghandy, MD, FRCPC
- Email: samiees@mcmaster.ca
- Phone: 1-905-521-2100
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.