Clinical trial NCT04025177: Indomethacin PK-PD in Extremely Preterm Neonates
Official title: Pharmacokinetics and Pharmacodynamics of Indomethacin Used for PDA Treatment in Extremely Preterm Neonates <27 Weeks Gestational Age
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Patent Ductus Arteriosus After Premature Birth
Keywords: Indomethacin
Pharmacokinetics
Preterm birth
Pharmacodynamics
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: St. Boniface Hospital
name: Health Sciences Centre, Winnipeg, Manitoba
name: University at Buffalo
First posted: 2019-07-18
Enrollment: 0
Sex: ALL
Minimum age (years): 23
Maximum age (years): 26
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Area under the curve from serial Indomethacin levels
timeFrame: At 48 hour following the last dose
Secondary outcomes:
measure: Percentage of Participants with Patent Ductus Arteriosus Closure
timeFrame: Within 48 hrs after the last dose
measure: Percentage of Participants with Intraventricular hemorrhage
timeFrame: Within the first 7 days of life.
measure: Duration of mechanical ventilation of each patient
timeFrame: trough hospital discharge, an average of up to 36 weeks gestational age
measure: Percentage of Participants with Adverse Events
timeFrame: trough hospital discharge, an average of up to 36 weeks gestational age
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital Research Centre
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
Study officials:
affiliation: University of Manitoba
name: Deepak Louis, MD
role: PRINCIPAL_INVESTIGATOR
References: