Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeUp to 28
SponsorHamilton Health Sciences Corporation
About this 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:
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Severe hyperbilirubinemia in need for exchange transfusion
Trial design
Design model
Parallel
Treatments tested in this trial
Standard Dose - Ibuprofen oral suspension
DrugStandard 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
DrugPrecision 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.
Treatment groups
26 Participants
are divided into 2 treatment groupsGroup A: Standard DosingActive comparator 1 intervention
Group B: Precision DosingExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Recruitment Feasibility
Feasibility will be assessed by the ability to randomize at least 15% of all eligible patients during the study period.
Time frame
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.
Time frame
From initial dose to 96 hours after3
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.
Time frame
From initial dose to 96 hours after4
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.
Time frame
From initial dose to 96 hours afterSecondary outcomes
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.
Time frame
From first dose to 72 hours2
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.
Time frame
From first dose to 72 hours3
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.
Time frame
From first dose to 72 hours4
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.
Time frame
From first dose to 14 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Hamilton Health Sciences Corporation
Lead sponsor
McMaster University
Collaborator
Hamilton Academic Health Sciences Organization
Collaborator
Source ClinicalTrials.gov