Recruiting
Phase 2

Ibuprofen

Sponsor:

Hamilton Health Sciences Corporation

Code:

NCT07143201

Conditions

Patent Ductus Arteriosus

Preterm

Eligibility Criteria

Sex: All

Age: 0

Healthy Volunteers: Not accepted

Interventions

Standard Dose - Ibuprofen oral suspension

Precision Dose - Ibuprofen oral suspension

Study Details

Brief 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.

Conditions

Patent Ductus Arteriosus

Preterm

Study ID

NCT07143201

Start date

Jul 4, 2024

Status verified date

Aug, 2025

Completion date

Jul, 2027

Anticipated

Primary completion date

Jul, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

26 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Standard Dosing

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

experimental: Precision Dosing

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).

Interventions

Standard Dose - Ibuprofen oral suspension

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 Dose - Ibuprofen oral suspension

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.

Primary outcome measure

  • Recruitment Feasibility [ Time Frame: From intial dose to 96 hours after. ]
  • Timeliness of PK Sample Result Availability [ Time Frame: From initial dose to 96 hours after ]
  • Timeliness of Top-up Dosing Data for Intervention Arm [ Time Frame: From initial dose to 96 hours after ]
  • Timely Completion of Daily Targeted Neonatal Echocardiogram (TnEcho) [ Time Frame: From initial dose to 96 hours after ]
  • Timely TnEcho Scoring and Model-Informed Precision Dosing (MIPD) Recommendation [ Time Frame: From initial dose to 96 hours after ]

Central Contacts and Locations

Central contacts

Samira Samiee-Zafarghandy, MD, FRCPC

1-905-521-2100samiees@mcmaster.ca

Locations

McMaster Children's Hospital - Neonatal Intensive Care Unit

Recruiting

Hamilton, Ontario, Canada, L8N 3Z2

Contacts

Samira Samiee-Zafarghandy, MD, FRCPC

1-905-521-2100samiees@mcmaster.ca

Heather Johnson, BScN

johnsh30@mcmaster.ca

Principal Investigator:

Samira Samiee-Zafarghandy, MD, FRCPC

More Information

Sponsor

Hamilton Health Sciences Corporation

Last update posted

Aug 27, 2025

Last verified

Aug, 2025

Keywords

  • MIPD-PDA
  • PDA
  • Precision Dosing
  • Ibuprofen

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Hamilton Health Sciences Corporation on 2025-08-27.