Indomethacin PK-PD in Extremely Preterm Neonates

Patent Ductus Arteriosus After Premature Birth Clinical Trial

— INDO  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04025177
• Other study ID #: B2018:095
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2020
• Est. completion date: February 2022

Study information

• Verified date: March 2020
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 26 Weeks

Eligibility

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)

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus After Premature Birth
• Premature Birth

Intervention

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.

Locations

Country	Name	City	State
Canada	Health Sciences Centre	Winnipeg	Manitoba
Canada	St. Boniface General Hospital Research Centre	Winnipeg	Manitoba

Sponsors (4)

Lead Sponsor	Collaborator
University of Manitoba	Health Sciences Centre, Winnipeg, Manitoba, St. Boniface Hospital, University at Buffalo

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants with Patent Ductus Arteriosus Closure	Confirmed by echocardiogram	Within 48 hrs after the last dose
Secondary	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.
Secondary	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
Secondary	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