Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT

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

Interventions

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• McMaster University

  collaborator OTHER

• Hamilton Academic Health Sciences Organization

  collaborator OTHER

• Hamilton Health Sciences Corporation

  lead OTHER

Principal Investigators

• Samira Samiee-Zafarghandy, MD, FRCPC · McMaster University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Max Age

28 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-04

Primary Completion

2026-07-31

Completion

2027-07-31

Countries

• Canada

Study Locations