Indomethacin PK-PD in Extremely Preterm Neonates

NCT ID: NCT04025177

Last Updated: 2021-10-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-31
• Study Completion Date: 2022-02-28

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.

Conditions

Patent Ductus Arteriosus After Premature Birth

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Indomethacin Injection

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 23 Weeks
• Maximum Eligible Age: 26 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Boniface Hospital

OTHER

Sponsor Role: collaborator

Health Sciences Centre, Winnipeg, Manitoba

OTHER

Sponsor Role: collaborator

University at Buffalo

OTHER

Sponsor Role: collaborator

University of Manitoba

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deepak Louis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

St. Boniface General Hospital Research Centre

Winnipeg, Manitoba, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

Countries

Canada

Other Identifiers

B2018:095

Identifier Type: -

Identifier Source: org_study_id