Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT
Model Informed Precision Dosing of Oral Ibuprofen for Treatment of Persistent Patent Ductus Arteriosus: A Pilot Randomized Controlled Feasibility Trial
Hamilton Health Sciences Corporation
26 participants
Jul 4, 2024
INTERVENTIONAL
Conditions
Summary
Newborns born early are at risk for a serious health problem called patent ductus arteriosus (PDA). PDA is a passageway between heart and lung that can cause life-threatening complications such as bleeding in the brain or even death if it remains open and large. When closure of PDA is needed, doctors make every attempt to do it as soon as possible. Ibuprofen is the best drug to close the PDA, but it only works for 50% of small newborns. The investigators have shown before that small newborns handle ibuprofen differently and the amount of active ibuprofen that reaches their blood can be very unpredictable. Studies have shown if enough ibuprofen reaches the body, it can close the PDA. Therefore the investigators designed this study to see whether it is possible to give each newborn the right amount of ibuprofen that their body needs to close the PDA. The investigators will compare two ways to give ibuprofen in a small number of newborns: 1 - standard amount of ibuprofen to everyone, which is the usual care or 2 - ibuprofen doses that will be changed based on how much active ibuprofen has reached the body and how well the newborn's PDA is closing. The investigators will then compare the number of PDAs closed in each group and closely monitor any possible challenges for this new practice. By doing this project, the goals can be summarized as below: A. Primary goal: To determine if it is feasible to successfully run a larger study in the future. B. Secondary goals 1. To assess how well and how safely the personalized (MIPD) method works, using a tool called WAPPS-PDA to guide dosing. 2. To compare the effectiveness and safety of the personalized method with standard ibuprofen dosing. 3. To identify drug levels in the blood (Cmin, AUC0-24, AUC0-72) that are associated with complete, partial, or no response to treatment.
Eligibility
Inclusion Criteria4
- 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 Criteria10
- 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)
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Interventions
Standard dosing administers ibuprofen without adjustments, starting with an initial loading dose followed by two maintenance doses at 24-hour intervals: 10/5/5 mg/kg for infants aged ≤72 hours, and 20/10/10 mg/kg for those \>72 hours old.
Precision Dosing (Model-Informed Precision Dosing - MIPD): Begins with the same initial loading dose as the Standard Dosing arm, with subsequent doses adjusted based on a Bayesian forecasting model that integrates real-time PK and echocardiographic data.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07143201