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NCT Number: NCT07143201

Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT

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.

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Key information

Conditions

Patent Ductus Arteriosus Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Ductus Arteriosus, Patent Female Urogenital Diseases and Pregnancy Complications Heart Defects, Congenital Heart Diseases Obstetric Labor Complications Obstetric Labor, Premature Pregnancy Complications Premature Birth Preterm Urogenital Diseases

Age range

Up to 28 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

McMaster Children's Hospital - Neonatal Intensive Care Unit

Hamilton, Ontario, L8N 3Z2, Canada

Location status: Recruiting

Location contact

Heather Johnson, BScN

CONTACT

[email protected]

Samira Samiee-Zafarghandy, MD, FRCPC

CONTACT

[email protected]

1-905-521-2100 ext. 73568

Samira Samiee-Zafarghandy, MD, FRCPC

PRINCIPAL_INVESTIGATOR

About this study

Study Design Overview:

This clinical trial is a single-center, pilot, randomized, controlled, triple-blind study designed to evaluate the feasibility and effectiveness of model-informed precision dosing (MIPD) of oral ibuprofen compared to standard dosing for the treatment of Patent Ductus Arteriosus (PDA) in preterm neonates (≤27+6 weeks gestational age). The trial assesses both operational feasibility and clinical outcomes, with a focus on the use of a pharmacokinetic (PK) prediction module provided by the Web-Accessible Population Pharmacokinetics Service-PDA (WAPPS-PDA).

  • Standard Dosing Arm: Participants in this arm receive the standard oral ibuprofen regimen used in the unit. Treatment begins with an initial loading dose, followed by two smaller doses administered at 24-hour intervals. While PK samples and targeted echocardiograms are collected at the same intervals as in the precision dosing arm, these data points do not influence dosing decisions.
  • Model-Informed Precision Dosing (MIPD) Arm: Participants in this arm initially receive the same loading dose of ibuprofen as those in the standard dosing arm. Subsequent doses are adjusted using real-time PK data and echocardiographic evaluations through the WAPPS-PDA tool. This tool employs a Bayesian forecasting model to analyze blood samples collected at 6, 30, and 54 hours post-initial dose, combining these results with the PDA response level noted in the targeted echocardiograms to dynamically adjust dosing. Dose adjustments are reviewed every 12 hours to ensure tailored treatment based on the neonate's specific pharmacological response, optimizing the chances of effective PDA closure.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Standard Dose - Ibuprofen oral suspension

Drug

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

Drug

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 outcomes

  1. Recruitment Feasibility

    Time frame: From intial dose to 96 hours after.

    Feasibility will be assessed by the ability to randomize at least 15% of all eligible patients during the study period.

  2. Timeliness of PK Sample Result Availability

    Time frame: From initial dose to 96 hours after

    Feasibility will be assessed by the ability to obtain results for at least 80% of pharmacokinetic (PK) samples within 4 hours of sample collection.

  3. Timeliness of Top-up Dosing Data for Intervention Arm

    Time frame: From initial dose to 96 hours after

    Feasibility will be assessed by the ability to generate dosing data for top-up administration within 14 hours of the previous dose in at least 80% of subjects in the intervention arm.

  4. Timely Completion of Daily Targeted Neonatal Echocardiogram (TnEcho)

    Time frame: From initial dose to 96 hours after

    Feasibility will be assessed by the ability to perform daily TnEcho within 4 to 8 hours prior to the next scheduled dose in at least 80% of subjects.

  5. Timely TnEcho Scoring and Model-Informed Precision Dosing (MIPD) Recommendation

    Time frame: From initial dose to 96 hours after

    Feasibility will be assessed by the ability to score the TnEcho, assign responsiveness grouping, and provide the MIPD recommendation for the second and third doses of oral ibuprofen within 24 hours of the previous dose in at least 80% of subjects.

Secondary outcomes

  1. Achievement of Target Trough Concentration and AUC (Intervention Arm Only)

    Time frame: From first dose to 72 hours

    This exploratory outcome will evaluate the proportion of participants in the intervention arm who reach the predefined target trough concentration, AUC₀-₂₄, and AUC₀-₇₂. Results will be summarized descriptively and compared within the intervention group.

  2. Maximum Ibuprofen Concentration (Cmax) ≤80 µg/mL (Intervention Arm Only)

    Time frame: From first dose to 72 hours

    This outcome will assess the proportion of intervention-arm participants whose maximum ibuprofen concentration (Cmax) remains at or below the predefined limit of 80 µg/mL. Results will be described and compared to the predefined threshold.

  3. Daily Ibuprofen Dose ≤40 mg/kg (Intervention Arm Only)

    Time frame: From first dose to 72 hours

    This outcome will evaluate the proportion of participants in the intervention arm whose daily ibuprofen dose does not exceed 40 mg/kg. The frequency of participants meeting this dosing threshold will be summarized descriptively.

  4. Closure of the Patent Ductus Arteriosus (PDA)

    Time frame: From first dose to 14 days

    This outcome will assess the proportion of participants with echocardiographically confirmed closure of the PDA following treatment. Results will be summarized and compared across study groups.

  5. Need for Repeat Pharmacotherapy

    Time frame: From first dose to 14 Days

    This outcome will evaluate the proportion of participants requiring a repeat course of pharmacologic PDA treatment within 14 days of completing the initial course. Findings will be reported descriptively.

  6. Need for Surgical Ligation

    Time frame: From first dose to 14 Days

    This outcome will assess the proportion of participants who require surgical ligation of the PDA due to persistent patency or clinical deterioration. Results will be summarized for both study groups.

  7. Treatment Interruption

    Time frame: From first dose to 14 Days

    This outcome will describe the proportion of participants whose ibuprofen treatment was interrupted prior to completion due to clinical or safety concerns. Outcomes will be compared descriptively.

  8. Occurrence of Adverse Events

    Time frame: From first dose to 14 Days

    This outcome will describe the proportion of participants who experience at least one adverse event during the follow-up period. Events will be classified by severity and relatedness to the study drug, and summarized descriptively.

Study contacts

Contact information is provided by the study sponsor or research team.

Samira Samiee-Zafarghandy, MD, FRCPC

CONTACT

[email protected]

1-905-521-2100 ext. 73568

Sponsors and collaborators

Lead sponsor

Hamilton Health Sciences Corporation

Other

Collaborators

  • Hamilton Academic Health Sciences Organization
  • McMaster University

Registry information

Official study title

Model Informed Precision Dosing of Oral Ibuprofen for Treatment of Persistent Patent Ductus Arteriosus: A Pilot Randomized Controlled Feasibility Trial

Acronym: MIPD-PDA

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Aug 27, 2025
Registry last updated
Aug 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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