Indomethacin PK-PD in Extremely Preterm Neonates

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

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.

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.

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)