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Patent Ductus ArteriosusPhase 2MIPD-PDANCT07143201

Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT

A Phase 2 study testing Standard Dose - Ibuprofen oral suspension and Precision Dose - Ibuprofen oral suspension in people with Patent Ductus Arteriosus and Preterm, run by Hamilton Health Sciences Corporation at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 28 weeks
Conditions the study is for
Patent Ductus Arteriosus, Preterm
What is being tested?
Standard Dose - Ibuprofen oral suspension and Precision Dose - Ibuprofen oral suspension
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteCanada
Study dates
4 Jul 2024to Jul 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 28 weeks
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 10Show fewer
  • Necrotizing enterocolitis (NEC)
  • Gastrointestinal perforation
  • Active bleeding
  • Severe thrombocytopenia (< 50× 109/L)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Samira Samiee-Zafarghandy, MD, FRCPC contact

1-905-521-2100 ext. 73568

samiees@mcmaster.ca

Canada1 site, 1 recruiting
  • McMaster Children's Hospital - Neonatal Intensive Care Unit

    Hamilton, Ontario, L8N 3Z2

    Samira Samiee-Zafarghandy, MD, FRCPC, 1-905-521-2100 ext. 73568, samiees@mcmaster.ca

    Heather Johnson, BScN, johnsh30@mcmaster.ca

    Recruiting

Other trials in Canada

About this study

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

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:

  1. Primary goal: To determine if it is feasible to successfully run a larger study in the future.
  2. Secondary goals
  3. To assess how well and how safely the personalized (MIPD) method works, using a tool called WAPPS-PDA to guide dosing.
  4. To compare the effectiveness and safety of the personalized method with standard ibuprofen dosing.
  5. To identify drug levels in the blood (Cmin, AUC0-24, AUC0-72) that are associated with complete, partial, or no response to treatment.
Read the detailed description

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.
Being tested
Standard Dose - Ibuprofen oral suspension, Precision Dose - Ibuprofen oral suspension
Keywords
MIPD-PDA, PDA, Precision Dosing, Ibuprofen
Medical subject headings
Ductus Arteriosus, Patent, Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard Dose - Ibuprofen oral suspensionDrug

    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 suspensionDrug

    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.

Study groups in NCT07143201
Study groupRoleWhat they receive
Standard DosingActive comparatorPNA-based standard dosing of ibuprofen [ <= 72 hours PNA: 10/5/5 q24hrs vs >72 hours PNA 20/10/10 q24hrs].
Receives: Drug: Standard Dose - Ibuprofen oral suspension
Precision DosingExperimentalPNA-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).
Receives: Drug: Precision Dose - Ibuprofen oral suspension

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recruitment Feasibility

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

    Measured: From intial dose to 96 hours after.

  2. Timeliness of PK Sample Result Availability

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

    Measured: From initial dose to 96 hours after

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

    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.

    Measured: From initial dose to 96 hours after

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

    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.

    Measured: From initial dose to 96 hours after

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

    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.

    Measured: From initial dose to 96 hours after

Secondary outcomes (8)
  1. Achievement of Target Trough Concentration and AUC (Intervention Arm Only)

    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.

    Measured: From first dose to 72 hours

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

    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.

    Measured: From first dose to 72 hours

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

    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.

    Measured: From first dose to 72 hours

  4. Closure of the Patent Ductus Arteriosus (PDA)

    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.

    Measured: From first dose to 14 days

  5. Need for Repeat Pharmacotherapy

    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.

    Measured: From first dose to 14 Days

  6. Need for Surgical Ligation

    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.

    Measured: From first dose to 14 Days

  7. Treatment Interruption

    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.

    Measured: From first dose to 14 Days

  8. Occurrence of Adverse Events

    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.

    Measured: From first dose to 14 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2025
  2. Study start4 Jul 2024
  3. Primary completionJul 2026 (estimated)
  4. Study completionJul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Care provider, Outcomes assessor
Enrolment
26 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07143201
Sponsor's protocol ID
HiREB #16287
Acronym
MIPD-PDA
Status last verified
Aug 2025
First submitted
8 Aug 2025
Last updated
27 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: This is a pilot feasibility study with a small sample size, and there are no current plans for data sharing.

Publications

  • McEneny-King A, Foster G, Iorio A, Edginton AN. Data Analysis Protocol for the Development and Evaluation of Population Pharmacokinetic Models for Incorporation Into the Web-Accessible Population Pharmacokinetic Service - Hemophilia (WAPPS-Hemo). JMIR Res Protoc. 2016 Dec 7;5(4):e232. doi: 10.2196/resprot.6559.

    PubMed 27927609
  • Euteneuer JC, Kamatkar S, Fukuda T, Vinks AA, Akinbi HT. Suggestions for Model-Informed Precision Dosing to Optimize Neonatal Drug Therapy. J Clin Pharmacol. 2019 Feb;59(2):168-176. doi: 10.1002/jcph.1315. Epub 2018 Sep 11.

    PubMed 30204236
  • Van Overmeire B, Touw D, Schepens PJ, Kearns GL, van den Anker JN. Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus. Clin Pharmacol Ther. 2001 Oct;70(4):336-43.

    PubMed 11673749
  • Hirt D, Van Overmeire B, Treluyer JM, Langhendries JP, Marguglio A, Eisinger MJ, Schepens P, Urien S. An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study. Br J Clin Pharmacol. 2008 May;65(5):629-36. doi: 10.1111/j.1365-2125.2008.03118.x. Epub 2008 Feb 27.

    PubMed 18307541
  • Engbers AGJ, Voller S, Flint RB, Goulooze SC, de Klerk J, Krekels EHJ, van Dijk M, Willemsen SP, Reiss IKM, Knibbe CAJ, Simons SHP. The Effect of Ibuprofen Exposure and Patient Characteristics on the Closure of the Patent Ductus Arteriosus in Preterm Infants. Clin Pharmacol Ther. 2022 Aug;112(2):307-315. doi: 10.1002/cpt.2616. Epub 2022 May 6.

    PubMed 35429165
  • Barzilay B, Youngster I, Batash D, Keidar R, Baram S, Goldman M, Berkovitch M, Heyman E. Pharmacokinetics of oral ibuprofen for patent ductus arteriosus closure in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2012 Mar;97(2):F116-9. doi: 10.1136/adc.2011.215160. Epub 2011 Aug 11.

    PubMed 21840880
  • Samiee-Zafarghandy S, van Donge T, Fusch G, Pfister M, Jacob G, Atkinson A, Rieder MJ, Smit C, Van Den Anker J. Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates. Arch Dis Child. 2022 Jan;107(1):86-91. doi: 10.1136/archdischild-2020-321381. Epub 2021 May 11.

    PubMed 33975823
  • Mitra S, Florez ID, Tamayo ME, Mbuagbaw L, Vanniyasingam T, Veroniki AA, Zea AM, Zhang Y, Sadeghirad B, Thabane L. Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis. JAMA. 2018 Mar 27;319(12):1221-1238. doi: 10.1001/jama.2018.1896.

    PubMed 29584842

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard Dose - Ibuprofen oral suspension and Precision Dose - Ibuprofen oral suspension in people with Patent Ductus Arteriosus and Preterm, run by Hamilton Health Sciences Corporation at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Samira Samiee-Zafarghandy, MD, FRCPC (1-905-521-2100 ext. 73568, samiees@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recruitment Feasibility (time frame: From intial dose to 96 hours after.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07143201, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025.

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