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Indomethacin PK-PD in Extremely Preterm Neonates (INDO)

Primary Purpose

Patent Ductus Arteriosus After Premature Birth

Status

Withdrawn

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Indomethacin Injection

About this trial

This is an interventional treatment trial for Patent Ductus Arteriosus After Premature Birth focused on measuring Indomethacin, Pharmacokinetics, Preterm birth, Pharmacodynamics

Eligibility Criteria

23 Weeks - 26 Weeks (Child)All SexesDoes not accept 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)

Sites / Locations

St. Boniface General Hospital Research Centre
Health Sciences Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neonates with an open PDA

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Percentage of Participants with Patent Ductus Arteriosus Closure

Confirmed by echocardiogram

Percentage of Participants with Intraventricular hemorrhage

Confirmed by cranial ultrasound performed and graded using Papile's classification system

Duration of mechanical ventilation of each patient

Number of days the infant was intubated and ventilated.

Percentage of Participants with Adverse Events

development of any type A adverse reactions in the infants receiving indomethacin therapy

Full Information

NCT ID

NCT04025177

First Posted

May 27, 2019

Last Updated

September 28, 2021

Sponsor

University of Manitoba

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04025177

Brief Title

Indomethacin PK-PD in Extremely Preterm Neonates

Acronym

INDO

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Halted due to feasibility issues

Study Start Date

January 2020 (Anticipated)

Primary Completion Date

August 2021 (Anticipated)

Study Completion Date

February 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Manitoba

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Patent Ductus Arteriosus After Premature Birth

Keywords

Indomethacin, Pharmacokinetics, Preterm birth, Pharmacodynamics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Neonates with an open PDA

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Indomethacin Injection

Intervention Description

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.

Primary Outcome Measure Information:

Title

Area under the curve from serial Indomethacin levels

Description

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 Outcome Measure Information:

Title

Percentage of Participants with Patent Ductus Arteriosus Closure

Description

Confirmed by echocardiogram

Time Frame

Within 48 hrs after the last dose

Title

Percentage of Participants with Intraventricular hemorrhage

Description

Confirmed by cranial ultrasound performed and graded using Papile's classification system

Time Frame

Within the first 7 days of life.

Title

Duration of mechanical ventilation of each patient

Description

Number of days the infant was intubated and ventilated.

Time Frame

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

Title

Percentage of Participants with Adverse Events

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

23 Weeks

Maximum Age & Unit of Time

26 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Deepak Louis, MD

Organizational Affiliation

University of Manitoba

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Boniface General Hospital Research Centre

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R2H 2A6

Country

Canada

Facility Name

Health Sciences Centre

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3A 1R9

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

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Indomethacin PK-PD in Extremely Preterm Neonates

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