Clinical trial NCT04019106: Budesonide With Intratracheal Surfactants in Extremely Preterm Infants
Official title: Pharmacokinetics and Pharmacodynamics of Budesonide With Intratracheal Surfactant (BITS) Administration in Preterm Infants < 29 Weeks Gestational Age
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Bronchopulmonary Dysplasia
Respiratory Distress Syndrome in Premature Infant
Keywords: Surfactant
Budesonide
Steroid
Intratracheal
Preterm
Bronchopulmonary Dysplasia
Respiratory Distress Syndrome
Bovine Lipid Extract Surfactant
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: Health Sciences Centre, Winnipeg, Manitoba
name: St. Boniface Hospital
name: Manitoba Institute of Child Health
name: University of Utah
name: Winnipeg Rh Institute Foundation Inc.
name: BLES Biochemicals Inc.
First posted: 2019-07-15
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This is a phase I/II trial in preterm infants aimed at identifying the optimal dose of budesonide with bovine lipid extract surfactant as vehicle for intratracheal administration.

Detailed description: Premature infants of gestational age less than 29 weeks with respiratory distress syndrome and clinical indication for surfactant administration will be recruited for this Phase I/II open-label study.

A total of 30 subjects will be recruited from 2 neonatal intensive care units:

1. Children's Hospital-Health Sciences Centre (HSC), Winnipeg
2. St. Boniface General Hospital, Winnipeg, MB

3 groups of 10 infants each will receive single dose of intratracheal budesonide (0.0625 mg/kg, 0.125 mg/kg, and 0.25 mg/kg) with BLES surfactant (5 ml/kg). PK/PD analysis will be done using clinical parameters, serum biomarkers, tracheal aspirate biomarkers and plasma budesonide levels obtained at fixed intervals.

The duration of subject participation will involve 12-17 weeks for the clinical intervention, depending on gestational age at birth and discharge date. Participants will be followed until 40 weeks or discharge, whichever comes first.

Eligibility criteria: Inclusion Criteria:

1. Male or female infant born between 23 and 28+6 weeks of GA
2. Infant diagnosed with RDS according to clinical protocol criteria
3. Able to adhere to surfactant administration protocol
4. The patient is born in the study centre.
5. 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.
6. 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:

1. Older than five days at inclusion.
2. Presence of known clinically significant congenital heart disease or other major congenital malformation
3. Subjects with clinically significant laboratory abnormalities which are deemed by the investigator to represent a safety risk to participation in this study. Other laboratory parameters outside the reference range for the subject's age may be included if the investigator considers the abnormalities unlikely to introduce additional risk factors and will not interfere with data interpretation.

Primary outcomes:
measure: Area under the curve from serial budesonide levels
timeFrame: At 24 hour time point following dosing
Secondary outcomes:
measure: Bronchopulmonary Dysplasia free survival
timeFrame: at 36 weeks PMA or discharge, whichever comes first
measure: Neonatal Mortality
timeFrame: up to 40 weeks PMA or discharge, whichever comes first
measure: Concentration of Inflammatory Biomarkers in Tracheal Aspirates
timeFrame: Baseline, 24 hours, 48 hours,1 week, 4 weeks and 36 weeks Gestational Age
measure: Concentration of Inflammatory Biomarkers in Serum
timeFrame: Baseline, 24 hours, 48 hours and 1 week.
measure: Duration of Hospital Stay
timeFrame: from day 0 (birth date) to 40 weeks
measure: VentilationStrategy
timeFrame: till 36 weeks PMA or discharge, whichever comes first
measure: Respiratory Severity Score
timeFrame: at baseline and till 36 weeks PMA or discharge, whichever comes first
measure: Duration of Supplemental Oxygen
timeFrame: till 36 weeks PMA or discharge, whichever comes first
measure: Level of Supplemental Oxygen Administered
timeFrame: at baseline and at 36 week Post menstrual age or discharge, whichever comes first
measure: Presence of Respiratory Support
timeFrame: at 36 week Post menstrual age or discharge, whichever comes first
measure: Percentage of Participants with Pulmonary Hemorrhage
timeFrame: at baseline and 48 hours after budesonide with surfactant administration
measure: Percentage of Participants with Hypothalamic pituitary axis (HPA) suppression
timeFrame: at 0 and 24 hours after dosing
measure: Percentage of Participants with Pneumothorax on Chest X-ray
timeFrame: at baseline and 48 hours after budesonide with surfactant administration
measure: Percentage of Participants with Spontaneous Intestinal Perforation (SIP) on abdominal X-ray
timeFrame: at baseline and 48 hours after budesonide with surfactant administration
measure: Percentage of Participants with Intra-ventricular Hemorrhage
timeFrame: at baseline and 48 hours after budesonide with surfactant administration
measure: Percentage of Participants with Sepsis
timeFrame: at baseline and till 36 weeks PMA or discharge, whichever comes first
measure: Percentage of Participants with Necrotising Enterocolitis (NEC)
timeFrame: 48 hours after budesonide with surfactant administration
measure: Percentage of Participants with Severe Retinopathy at Prematurity
timeFrame: baseline and 48 hours after budesonide with surfactant administration
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Children's Hospital-Health Science Centre
state: Manitoba
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
Study officials:
affiliation: Children's Hospital Research Institute of Manitoba
name: Geert W 't Jong, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: