A Multi-center Trial to Determine if Curosurf® Reduces the Duration of Mechanical Ventilation in Very Preterm Infants

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Controlled, Partially Double-blinded, Phase 3, Multi-center Trial to Determine if Curosurf® Reduces the Duration of Mechanical Ventilation in Infants 24+0 to 31+6 Weeks Gestational Age

Conditions
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Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Curosurf-Group1
* Drug: BLES-group 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born between 24+0 and 31+6 weeks gestational age, admitted to the study centers Infants with RDS requiring intubation and surfactant therapy within 48 hours after birth Exclusion Criteria: Any infant more than 48 hours of age Any infant with a pulmonary hemorrhage Any infant with life-threatening congenital anomaly or one that is considered non-viable Any infant on rescue high frequency ventilation Any infant known to require early intubation and ventilation for surgical treatment of a congenital anomaly Any infant with anomalies of the upper or lower airway or mandible precluding use of nCPAP Any infant born after prolonged premature rupture of membranes (<22 weeks GA or >28 days prior to delivery) A parent/LAR who is incapable of, or unwilling, to give consent Participation in another clinical trial of any placebo, drug, biological, or device conducted under the provisions of a protocol Any other reason as deemed significant by the Investigator

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 31 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curosurf (Group 1)<br>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. | Drug: Curosurf-Group1<br>* Maximum of 3 doses are administered to infants diagnosed with RDS.<br>|
| Active Comparator: BLES (Group 2)<br>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. | Drug: BLES-group 2<br>* Maximum of 3 doses are administered to infants with RDS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | rate on ventilator ≤40 per minute and mean airway pressure ≤ 10 cm H20 and fi02 ≤ 30% | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 36 weeks GA | 
| Curosurf-01 | 2. Duration of first intubation (in hours/days) | 36 weeks GA | 
| Curosurf-01 | 3. Total duration of respiratory support (ventilator and nCPAP) and total number of days of oxygen requirement | 36 weeks GA | 
| Curosurf-01 | 4. Number of doses of surfactant received | 36 weeks GA | 
| Curosurf-01 | 5. Adverse events during or after administration of surfactant | 36 weeks GA | 
| Curosurf-01 | 6. Bronchopulmonary dysplasia, defined as oxygen or respiratory support requirement at 36 weeks corrected GA | 36 Weeks GA | 
| Curosurf-01 | 7. Mortality prior to discharge | 36 weeks GA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prematurity