Indomethacin PK-PD in Extremely Preterm Neonates

University of Manitoba

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Patent Ductus Arteriosus After Premature Birth

Interventions

Indomethacin InjectionDRUG

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.

Eligibility

Sex: ALLMin age: 23 WeeksMax age: 26 Weeks

Medical Language ↔ Plain English

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)

Locations (2)

St. Boniface General Hospital Research Centre

Winnipeg, Manitoba, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

Outcomes

Primary Outcomes

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

Time frame: At 48 hour following the last dose

Secondary Outcomes

Percentage of Participants with Patent Ductus Arteriosus Closure

Confirmed by echocardiogram

Time frame: 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

Time frame: Within the first 7 days of life.

Duration of mechanical ventilation of each patient

Number of days the infant was intubated and ventilated.

Time frame: 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

Time frame: trough hospital discharge, an average of up to 36 weeks gestational age

Data from ClinicalTrials.gov

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