Indomethacin PK-PD in Extremely Preterm Neonates (INDO)

September 28, 2021 updated by: University of Manitoba

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.

Study Overview

Status

Withdrawn

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Health Sciences Centre
      • Winnipeg, Manitoba, Canada, R2H 2A6
        • St. Boniface General Hospital Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 5 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the curve from serial Indomethacin levels
Time Frame: 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
At 48 hour following the last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants with Patent Ductus Arteriosus Closure
Time Frame: Within 48 hrs after the last dose
Confirmed by echocardiogram
Within 48 hrs after the last dose
Percentage of Participants with Intraventricular hemorrhage
Time Frame: Within the first 7 days of life.
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
Time Frame: trough hospital discharge, an average of up to 36 weeks gestational age
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
Time Frame: 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
trough hospital discharge, an average of up to 36 weeks gestational age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Deepak Louis, MD, University of Manitoba

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2020

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

February 1, 2022

Study Registration Dates

First Submitted

May 27, 2019

First Submitted That Met QC Criteria

July 16, 2019

First Posted (Actual)

July 18, 2019

Study Record Updates

Last Update Posted (Actual)

October 6, 2021

Last Update Submitted That Met QC Criteria

September 28, 2021

Last Verified

March 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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