Budesonide With Intratracheal Surfactants in Extremely Preterm Infants

Bronchopulmonary Dysplasia Clinical Trial

— BITS  

Official title:

Pharmacokinetics and Pharmacodynamics of Budesonide With Intratracheal Surfactant (BITS) Administration in Preterm Infants < 29 Weeks Gestational Age

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04019106
• Other study ID #: BITS-03
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 15, 2019
• Est. completion date: January 15, 2021

Study information

• Verified date: August 2018
• Source: University of Manitoba
• Contact: Geert W 't Jong, MD, Ph.D
• Phone: (204)789-3206
• Email: gtjong[@]chrim.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: January 15, 2021
• Est. primary completion date: October 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 5 Days

Eligibility

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.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Respiratory Distress Syndrome in Premature Infant
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Budesonide in bovine lipid extract surfactant (BLES)
Budesonide in bovine lipid extract surfactant

Locations

Country	Name	City	State
Canada	Children's Hospital-Health Science Centre	Winnipeg	Manitoba
Canada	St. Boniface General Hospital	Winnipeg	Manitoba

Sponsors (7)

Lead Sponsor	Collaborator
University of Manitoba	BLES Biochemicals Inc., Health Sciences Centre, Winnipeg, Manitoba, Manitoba Institute of Child Health, St. Boniface General Hospital Research Centre, University of Utah, Winnipeg Rh Institute Foundation Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve from serial budesonide levels	Blood samples will be drawn from patients to determine the serum budesonide levels to determine the area under the curve	At 24 hour time point following dosing
Secondary	Bronchopulmonary Dysplasia free survival	NICHD criteria will be used to diagnose and grade the infants for presence of BPD.	at 36 weeks PMA or discharge, whichever comes first
Secondary	Neonatal Mortality	Survival of the infants	up to 40 weeks PMA or discharge, whichever comes first
Secondary	Concentration of Inflammatory Biomarkers in Tracheal Aspirates	Tracheal aspirates will be centrifuged to isolate a large aggregate surfactant fraction that will be assayed for both phospholipid (surfactant recovery) and total protein concentration. The supernatant fraction after surfactant isolation will be assayed for total protein, and selected cytokines (IL-1 ß, IL-6, IL-8, IL-10, CCL2 and TNF-?)	Baseline, 24 hours, 48 hours,1 week, 4 weeks and 36 weeks Gestational Age
Secondary	Concentration of Inflammatory Biomarkers in Serum	Cytokines IL-1 ß, IL-6, IL-8, IL-10, CCL2 and TNF-? will be analyzed in serum samples obtained from the infants following BITS administration using commercially available ELISA kits.	Baseline, 24 hours, 48 hours and 1 week.
Secondary	Duration of Hospital Stay		from day 0 (birth date) to 40 weeks
Secondary	VentilationStrategy	Duration and modality of ventilation used in the preterm infants	till 36 weeks PMA or discharge, whichever comes first
Secondary	Respiratory Severity Score	The product of Fraction of inspired oxygen and mean airway pressure will be used to estimate the respiratory severity score	at baseline and till 36 weeks PMA or discharge, whichever comes first
Secondary	Duration of Supplemental Oxygen		till 36 weeks PMA or discharge, whichever comes first
Secondary	Level of Supplemental Oxygen Administered	the concentration of supplemental oxygen given at discharge or 36 weeks PMA compared to baseline.	at baseline and at 36 week Post menstrual age or discharge, whichever comes first
Secondary	Presence of Respiratory Support	the presence or absence of any method of respiratory support at discharge or 36 weeks PMA compared to baseline.	at 36 week Post menstrual age or discharge, whichever comes first
Secondary	Percentage of Participants with Pulmonary Hemorrhage	Clinical signs of pallor, cyanosis, bradycardia, apnoea and blood gas changes. Radiographic evidences of patchy infiltrates to complete opacification of lung fields.	at baseline and 48 hours after budesonide with surfactant administration
Secondary	Percentage of Participants with Hypothalamic pituitary axis (HPA) suppression	Cortisol levels will be measured	at 0 and 24 hours after dosing
Secondary	Percentage of Participants with Pneumothorax on Chest X-ray	Identified in X-ray as hyperlucent shadow outside the lungs without pulmonary vascular markings, with or without mediastinal shift	at baseline and 48 hours after budesonide with surfactant administration
Secondary	Percentage of Participants with Spontaneous Intestinal Perforation (SIP) on abdominal X-ray	Abdominal X-ray showing presence of free air. Presence or absence of SIP will be compared across the 3 dosing groups and within the dosing groups.	at baseline and 48 hours after budesonide with surfactant administration
Secondary	Percentage of Participants with Intra-ventricular Hemorrhage	presence or absence of will be compared across the 3 dosing groups and within the dosing groups.	at baseline and 48 hours after budesonide with surfactant administration
Secondary	Percentage of Participants with Sepsis	As per the third international consensus definitions for sepsis and septic shock (Sepsis-3)	at baseline and till 36 weeks PMA or discharge, whichever comes first
Secondary	Percentage of Participants with Necrotising Enterocolitis (NEC)	presence or absence of NEC will be compared across the 3 dosing groups and within the dosing groups.	48 hours after budesonide with surfactant administration
Secondary	Percentage of Participants with Severe Retinopathy at Prematurity	retinopathy of =grade III will be recorded	baseline and 48 hours after budesonide with surfactant administration