Indomethacin PK-PD in Extremely Preterm Neonates

Study Overview
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Brief Summary
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This is a phase II open-label study evaluating the pharmacokinetics and pharmacodynamics of targeted early use of indomethacin for PDA treatment in preterm neonates <27 weeks' gestational age.

Detailed Description
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Neonates will be enrolled following an echocardiogram performed within 12 hours after birth that confirms an open PDA (with no other contraindications for indomethacin treatment). After enrollment, neonates will receive intravenous indomethacin at a dose of 0.1mg/kg every 24 hours for 3 days. Indomethacin levels will be measured at regular intervals. Urine output and serum electrolytes will be monitored prior to each dose of indomethacin. An echocardiogram will be repeated after completion of indomethacin treatment (between 72-120 hours of age) to reassess the status of PDA.

Official Title
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Pharmacokinetics and Pharmacodynamics of Indomethacin Used for PDA Treatment in Extremely Preterm Neonates <27 Weeks Gestational Age

Conditions
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Patent Ductus Arteriosus After Premature Birth

Intervention / Treatment
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* Drug: Indomethacin Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female infant born between 23 (0/7) and 26 (6/7) week GA Infant diagnosed with PDA according to clinical protocol criteria Able to adhere to indomethacin administration protocol The patient is born in the study center. Subject's parent(s)/legal guardian(s) has provided signed and dated informed consent and authorization to use protected health information, as required by national and local regulations. In the investigator's opinion, the subject's parent(s)/legal guardian(s) understand(s) and can comply with protocol requirements, instructions, and protocol-stated restrictions, and is likely to complete the study as planned. Exclusion Criteria: known major congenital malformations (renal, cardiac, gastrointestinal and central nervous system) genetic syndromes-inborn errors of metabolism severe renal compromise intrauterine growth retardation with birth weight <3rd centile thrombocytopenia <50,000/mm3 moderate to severe pulmonary hypertension clinical sepsis -meningitis- hepatitis anticipated drug-drug-interactions (specifically CYP2C9, CYP2C19 and UGT 1-1)

Ages Eligible for Study
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Minimum Age: 23 Weeks
Maximum Age: 26 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neonates with an open PDA<br>Neonates born between 23 (0/7) and 26 (6/7) weeks gestational age with an open PDA, according to clinical protocol criteria, and no contraindication to the use of indomethacin. | Drug: Indomethacin Injection<br>* The dose of indomethacin will be 0.1 mg/kg/dose, based on birth weight, intravenously every 24 hours for a total of 3 doses. Doses 2 and 3 may be administered between 23.5 and 24.5 hours after the previous dose. Doses will be rounded to two significant figures.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from serial Indomethacin levels | Blood samples will be drawn from patients to determine the serum indomethacin levels to determine the area under the curve | At 48 hour following the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Patent Ductus Arteriosus Closure | Confirmed by echocardiogram | Within 48 hrs after the last dose | 
| Percentage of Participants with Intraventricular hemorrhage | Confirmed by cranial ultrasound performed and graded using Papile's classification system | Within the first 7 days of life. | 
| Duration of mechanical ventilation of each patient | Number of days the infant was intubated and ventilated. | trough hospital discharge, an average of up to 36 weeks gestational age | 
| Percentage of Participants with Adverse Events | development of any type A adverse reactions in the infants receiving indomethacin therapy | trough hospital discharge, an average of up to 36 weeks gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Indomethacin, Pharmacokinetics, Preterm birth, Pharmacodynamics