Respiratory Distress Syndrome
Conditions
Keywords
Prematurity
Brief summary
The purpose of this study is to see if a medication called Curosurf can reduce the length of time that small premature babies with Respiratory Distress Syndrome (immature lungs) or RDS, stay on the ventilator, as compared to the standard medication called BLES. Curosurf is a medication that is already used in other countries around the world but not yet in Canada. Babies born under 32 weeks of gestation frequently need respiratory support after birth, including being placed on a breathing machine or respirator. The most common reason is Respiratory Distress Syndrome (RDS) whereby immature lungs don't produce enough surfactant, a soapy like substance that helps the air sacs open and close. Our current standard treatment is a surfactant called BLES. Curosurf contains more active ingredient per volume therefore the amount is smaller. The investigators hypothesize that babies who receive Curosurf will be able to be removed from the ventilator sooner. Babies in this study will have a 50/50 chance of receiving either Curosurf or BLES and the investigators will monitor their progress during their Neonatal Intensive Care Unit admission. The study is taking place in Canada. The goal is to enroll 88 babies. There are no extra tests (blood tests or X-Rays) or return visits to the hospital for the purposes of this study.
Interventions
DRUGCurosurf-Group1
Maximum of 3 doses are administered to infants diagnosed with RDS.
DRUGBLES-group 2
Maximum of 3 doses are administered to infants with RDS
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
24 Weeks to 31 Weeks
Healthy volunteers
No
Inclusion criteria
1. Infants born between 24+0 and 31+6 weeks gestational age, admitted to the study centers 2. Infants with RDS requiring intubation and surfactant therapy within 48 hours after birth
Exclusion criteria
1. Any infant more than 48 hours of age 2. Any infant with a pulmonary hemorrhage 3. Any infant with life-threatening congenital anomaly or one that is considered non-viable 4. Any infant on rescue high frequency ventilation 5. Any infant known to require early intubation and ventilation for surgical treatment of a congenital anomaly 6. Any infant with anomalies of the upper or lower airway or mandible precluding use of nCPAP 7. Any infant born after prolonged premature rupture of membranes (\<22 weeks GA or \>28 days prior to delivery) 8. A parent/LAR who is incapable of, or unwilling, to give consent 9. Participation in another clinical trial of any placebo, drug, biological, or device conducted under the provisions of a protocol 10. Any other reason as deemed significant by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Objective of the Study is to Compare Between the Two Groups, the Number of Subjects Alive and Extubated at 48 Hours Post Surfactant Administration. Extubation | 48 hours | 1. rate on ventilator ≤40 per minute and 2. mean airway pressure ≤ 10 cm H20 and 3. fi02 ≤ 30% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Duration of Respiratory Support, Extubation Failure Rates, Need for Additional Surfactant Doses, Adverse Events (During and Following Administration), Survival and Pulmonary Morbidities During Hospital Admission Between the Two Groups. | 36 weeks GA | 1\. Extubation failure |
| Curosurf-01 | 36 weeks GA | 2\. Duration of first intubation (in hours/days) |
Countries
Canada
Participant flow
Recruitment details
Three university-affiliated tertiary NICUs recruited patients between March 2013 and December 2015. 560 patients were screening for eligibility.
Pre-assignment details
One patient in the Curosurf group was found to have an exclusion criteria after randomization and was excluded (he did not receive the assigned treatment).
Participants by arm
| Arm | Count |
|---|---|
| Curosurf (Group 1) Surfactant(Curosurf in this arm) is given for treatment of RDS after the diagnosis has been made by the Neonatologist. The treatment dose for Curosurf® is 2.5 ml/kg (200mg/kg) for the first dose and 1.25 ml/kg (100mg/kg) for repeat doses, given by endotracheal method. There is a maximum of 3 doses in the study.
Curosurf-Group1: Maximum of 3 doses are administered to infants diagnosed with RDS. | 42 |
| BLES (Group 2) Surfactant(BLES in this arm) is given for treatment of RDS after the diagnosis has been made by the Neonatologist. For BLES the recommended dose is 5 ml/kg. given by endotracheal method. There is a maximum of 3 doses in the study.
BLES-group 2: Maximum of 3 doses are administered to infants with RDS | 45 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Curosurf (Group 1) | BLES (Group 2) | Total |
|---|---|---|---|
| Age, Continuous | 26.5 weeks gestational age STANDARD_DEVIATION 1.5 | 26.9 weeks gestational age STANDARD_DEVIATION 2.1 | 26.7 weeks gestational age STANDARD_DEVIATION 1.9 |
| fraction of inspired oxygen | 45 % of inspired oxygen | 45 % of inspired oxygen | 45 % of inspired oxygen |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Canada | 42 participants | 45 participants | 87 participants |
| Sex: Female, Male Female | 23 Participants | 12 Participants | 35 Participants |
| Sex: Female, Male Male | 19 Participants | 33 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 42 | 1 / 45 |
| serious Total, serious adverse events | 5 / 42 | 11 / 45 |
Outcome results
Primary
The Primary Objective of the Study is to Compare Between the Two Groups, the Number of Subjects Alive and Extubated at 48 Hours Post Surfactant Administration. Extubation
1. rate on ventilator ≤40 per minute and 2. mean airway pressure ≤ 10 cm H20 and 3. fi02 ≤ 30%
Time frame: 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Curosurf (Group 1) | The Primary Objective of the Study is to Compare Between the Two Groups, the Number of Subjects Alive and Extubated at 48 Hours Post Surfactant Administration. Extubation | 21 Participants |
| BLES (Group 2) | The Primary Objective of the Study is to Compare Between the Two Groups, the Number of Subjects Alive and Extubated at 48 Hours Post Surfactant Administration. Extubation | 26 Participants |
Secondary
Curosurf-01
2\. Duration of first intubation (in hours/days)
Time frame: 36 weeks GA
Secondary
Curosurf-01
3\. Total duration of respiratory support (ventilator and nCPAP) and total number of days of oxygen requirement
Time frame: 36 weeks GA
Secondary
Curosurf-01
4\. Number of doses of surfactant received
Time frame: 36 weeks GA
Secondary
Curosurf-01
5\. Adverse events during or after administration of surfactant
Time frame: 36 weeks GA
Secondary
Curosurf-01
6\. Bronchopulmonary dysplasia, defined as oxygen or respiratory support requirement at 36 weeks corrected GA
Time frame: 36 Weeks GA
Secondary
Curosurf-01
7\. Mortality prior to discharge
Time frame: 36 weeks GA
Secondary
To Compare the Duration of Respiratory Support, Extubation Failure Rates, Need for Additional Surfactant Doses, Adverse Events (During and Following Administration), Survival and Pulmonary Morbidities During Hospital Admission Between the Two Groups.
1\. Extubation failure
Time frame: 36 weeks GA