Bronchopulmonary DysplasiaPhase 1/2BITSNCT04019106
Budesonide With Intratracheal Surfactants in Extremely Preterm Infants
A Phase 1/2 study testing Budesonide in bovine lipid extract surfactant (BLES) in people with Bronchopulmonary Dysplasia and Respiratory Distress Syndrome in Premature Infant, run by University of Manitoba at 2 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 1 hour to 5 days
- Conditions the study is for
- Bronchopulmonary Dysplasia, Respiratory Distress Syndrome in Premature Infant
- What is being tested?
- Budesonide in bovine lipid extract surfactant (BLES)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesCanada
- Study dates
- 15 Oct 2019to 15 Jan 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 5 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female infant born between 23 and 28+6 weeks of GA
- Infant diagnosed with RDS according to clinical protocol criteria
- Able to adhere to surfactant administration protocol
- The patient is born in the study centre.
- 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.
Who cannot join
- Older than five days at inclusion.
- Presence of known clinically significant congenital heart disease or other major congenital malformation
- 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.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Children's Hospital-Health Science Centre
Winnipeg, Manitoba, R3E 3P4
Geert 't Jong, MD, PhD, 2047893206, gtjong@chrim.ca
Abin Chandrakumar, PharmD, MSc, 2045945359, achandrakumar@chrim.ca
St. Boniface General Hospital
Winnipeg, Manitoba, R3E 3P4
Ruben Alvaro, MD, FAAP
About this study
Official title: Pharmacokinetics and Pharmacodynamics of Budesonide With Intratracheal Surfactant (BITS) Administration in Preterm Infants < 29 Weeks Gestational Age
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.
Read the 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:
- Children's Hospital-Health Sciences Centre (HSC), Winnipeg
- 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.
- Being tested
- Budesonide in bovine lipid extract surfactant (BLES)
- Keywords
- Surfactant, Budesonide, Steroid, Intratracheal, Preterm, Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Bovine Lipid Extract Surfactant
- Medical subject headings
- Bronchopulmonary Dysplasia, Premature Birth, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Budesonide in bovine lipid extract surfactant (BLES)Drug
Also called Pulmicort respule, BLES
Budesonide in bovine lipid extract surfactant
| Study group | Role | What they receive |
|---|---|---|
| Dosing Level 1 | Experimental | 0.0625 mg/kg Budesonide in bovine lipid extract surfactant (BLES) Receives: Drug: Budesonide in bovine lipid extract surfactant (BLES) |
| Dosing Level 2 | Experimental | 0.125 mg/kg Budesonide in bovine lipid extract surfactant (BLES) Receives: Drug: Budesonide in bovine lipid extract surfactant (BLES) |
| Dosing Level 3 | Experimental | 0.25 mg/kg Budesonide in bovine lipid extract surfactant (BLES) Receives: Drug: Budesonide in bovine lipid extract surfactant (BLES) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At 24 hour time point following dosing
Secondary outcomes (18)
Bronchopulmonary Dysplasia free survival
NICHD criteria will be used to diagnose and grade the infants for presence of BPD.
Measured: at 36 weeks PMA or discharge, whichever comes first
Neonatal Mortality
Survival of the infants
Measured: up to 40 weeks PMA or discharge, whichever comes first
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 β, IL-6, IL-8, IL-10, CCL2 and TNF-ɑ)
Measured: Baseline, 24 hours, 48 hours,1 week, 4 weeks and 36 weeks Gestational Age
Concentration of Inflammatory Biomarkers in Serum
Cytokines IL-1 β, IL-6, IL-8, IL-10, CCL2 and TNF-ɑ will be analyzed in serum samples obtained from the infants following BITS administration using commercially available ELISA kits.
Measured: Baseline, 24 hours, 48 hours and 1 week.
Duration of Hospital Stay
Measured: from day 0 (birth date) to 40 weeks
VentilationStrategy
Duration and modality of ventilation used in the preterm infants
Measured: till 36 weeks PMA or discharge, whichever comes first
Respiratory Severity Score
The product of Fraction of inspired oxygen and mean airway pressure will be used to estimate the respiratory severity score
Measured: at baseline and till 36 weeks PMA or discharge, whichever comes first
Duration of Supplemental Oxygen
Measured: till 36 weeks PMA or discharge, whichever comes first
Level of Supplemental Oxygen Administered
the concentration of supplemental oxygen given at discharge or 36 weeks PMA compared to baseline.
Measured: at baseline and at 36 week Post menstrual age or discharge, whichever comes first
Presence of Respiratory Support
the presence or absence of any method of respiratory support at discharge or 36 weeks PMA compared to baseline.
Measured: at 36 week Post menstrual age or discharge, whichever comes first
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.
Measured: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Hypothalamic pituitary axis (HPA) suppression
Cortisol levels will be measured
Measured: at 0 and 24 hours after dosing
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
Measured: at baseline and 48 hours after budesonide with surfactant administration
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.
Measured: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Intra-ventricular Hemorrhage
presence or absence of will be compared across the 3 dosing groups and within the dosing groups.
Measured: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Sepsis
As per the third international consensus definitions for sepsis and septic shock (Sepsis-3)
Measured: at baseline and till 36 weeks PMA or discharge, whichever comes first
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.
Measured: 48 hours after budesonide with surfactant administration
Percentage of Participants with Severe Retinopathy at Prematurity
retinopathy of ≥grade III will be recorded
Measured: baseline and 48 hours after budesonide with surfactant administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2019
- Study start15 Oct 2019 (estimated)
- Primary completion15 Oct 2020 (estimated)
- Study completion15 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- Health Sciences Centre, Winnipeg, Manitoba, St. Boniface Hospital, Manitoba Institute of Child Health, University of Utah, Winnipeg Rh Institute Foundation Inc., BLES Biochemicals Inc.
- Responsible party
- Sponsor
- Investigators
- Geert W 't Jong, MD, Ph.D, Principal investigator, Children's Hospital Research Institute of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04019106
- Sponsor's protocol ID
- BITS-03
- Acronym
- BITS
- Status last verified
- Aug 2018
- First submitted
- 15 Aug 2018
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of Budesonide With Intratracheal Surfactant (BITS) Administration in Preterm Infants < 29 Weeks Gestational Age
- ClinicalTrials.gov ID
- NCT04019106
- Acronym / sponsor ID
- BITS / BITS-03
- Keywords
- Surfactant, Budesonide, Steroid, Intratracheal, Preterm, Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Bovine Lipid Extract Surfactant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- Health Sciences Centre, Winnipeg, Manitoba, St. Boniface Hospital, Manitoba Institute of Child Health, University of Utah, Winnipeg Rh Institute Foundation Inc., BLES Biochemicals Inc.
- Study start
- 15 Oct 2019 (estimated)
- Primary completion
- 15 Oct 2020 (estimated)
- Study completion
- 15 Jan 2021 (estimated)
- First posted
- 15 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Children's Hospital-Health Sciences Centre (HSC), Winnipeg
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dosing Level 1 | Experimental | Drug: Budesonide in bovine lipid extract surfactant (BLES)0.0625 mg/kg Budesonide in bovine lipid extract surfactant (BLES) |
| Dosing Level 2 | Experimental | Drug: Budesonide in bovine lipid extract surfactant (BLES)0.125 mg/kg Budesonide in bovine lipid extract surfactant (BLES) |
| Dosing Level 3 | Experimental | Drug: Budesonide in bovine lipid extract surfactant (BLES)0.25 mg/kg Budesonide in bovine lipid extract surfactant (BLES) |
Who may qualify
- Ages
- 1 hour to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male or female infant born between 23 and 28+6 weeks of GA
- Infant diagnosed with RDS according to clinical protocol criteria
- Able to adhere to surfactant administration protocol
- The patient is born in the study centre.
- 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.
Key exclusion criteria (3 listed)
- Older than five days at inclusion.
- Presence of known clinically significant congenital heart disease or other major congenital malformation
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Budesonide in bovine lipid extract surfactant (BLES)Also: Pulmicort respule, BLESBudesonide in bovine lipid extract surfactant | Drug | Dosing Level 1, Dosing Level 2, Dosing Level 3 |
Primary outcome
Area under the curve from serial budesonide levels
Time frame: At 24 hour time point following dosing
Blood samples will be drawn from patients to determine the serum budesonide levels to determine the area under the curve
18 secondary outcomes
Bronchopulmonary Dysplasia free survival
Time frame: at 36 weeks PMA or discharge, whichever comes first
Neonatal Mortality
Time frame: up to 40 weeks PMA or discharge, whichever comes first
Concentration of Inflammatory Biomarkers in Tracheal Aspirates
Time frame: Baseline, 24 hours, 48 hours,1 week, 4 weeks and 36 weeks Gestational Age
Concentration of Inflammatory Biomarkers in Serum
Time frame: Baseline, 24 hours, 48 hours and 1 week.
Duration of Hospital Stay
Time frame: from day 0 (birth date) to 40 weeks
VentilationStrategy
Time frame: till 36 weeks PMA or discharge, whichever comes first
Respiratory Severity Score
Time frame: at baseline and till 36 weeks PMA or discharge, whichever comes first
Duration of Supplemental Oxygen
Time frame: till 36 weeks PMA or discharge, whichever comes first
Level of Supplemental Oxygen Administered
Time frame: at baseline and at 36 week Post menstrual age or discharge, whichever comes first
Presence of Respiratory Support
Time frame: at 36 week Post menstrual age or discharge, whichever comes first
Percentage of Participants with Pulmonary Hemorrhage
Time frame: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Hypothalamic pituitary axis (HPA) suppression
Time frame: at 0 and 24 hours after dosing
Percentage of Participants with Pneumothorax on Chest X-ray
Time frame: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Spontaneous Intestinal Perforation (SIP) on abdominal X-ray
Time frame: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Intra-ventricular Hemorrhage
Time frame: at baseline and 48 hours after budesonide with surfactant administration
Percentage of Participants with Sepsis
Time frame: at baseline and till 36 weeks PMA or discharge, whichever comes first
Percentage of Participants with Necrotising Enterocolitis (NEC)
Time frame: 48 hours after budesonide with surfactant administration
Percentage of Participants with Severe Retinopathy at Prematurity
Time frame: baseline and 48 hours after budesonide with surfactant administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geert W 't Jong, MD, Ph.D principal investigator
Children's Hospital Research Institute of Manitoba
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Budesonide in bovine lipid extract surfactant (BLES) in people with Bronchopulmonary Dysplasia and Respiratory Distress Syndrome in Premature Infant, run by University of Manitoba at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Geert W 't Jong, MD, Ph.D ((204)789-3206, gtjong@chrim.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the curve from serial budesonide levels (time frame: At 24 hour time point following dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.