INDO: Indomethacin PK-PD in Extremely Preterm Neonates

Sponsor

University of Manitoba (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04025177

Collaborator

St. Boniface Hospital (Other), Health Sciences Centre, Winnipeg, Manitoba (Other), University at Buffalo (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Patent Ductus Arteriosus After Premature Birth	Drug: Indomethacin Injection	Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2021

Anticipated Study Completion Date :

Feb 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neonates with an open PDA 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 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.

Arm

Intervention/Treatment

Experimental: Neonates with an open PDA

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

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.

Outcome Measures

Primary Outcome Measures

Area under the curve from serial Indomethacin levels [At 48 hour following the last dose]
Blood samples will be drawn from patients to determine the serum indomethacin levels to determine the area under the curve

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

23 Weeks to 26 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)