NHFOV as Primary Support in Very Preterm Infants With RDS

Study Overview
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Brief Summary
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This will be a prospective, multi-center, two-arms,parallel, randomized, controlled trial with a superiority design,conducted in China. The investigators conduct this multi-centre, randomized, controlled trial to test the hypothesis that NHFOV is more effective than nCPAP in the treatment of respiratory distress syndrome (RDS) in infants with a gestational age of less than 28 weeks when used as a primary noninvasive ventilation (NIV) mode.

Detailed Description
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Preterm infants are eligible to the study if they they match the following inclusion criteria: (1) Gestational age between 240/7 and 286/7 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and a fraction of inspired oxygen (FiO2) greater than 0.25 for target saturation of peripheral oxygen (SpO2) 89% to 94%;; (3) Age less than 2 hours; (4)Informed parental consent has been obtained. Neonates will be randomized and assigned either to nCPAP or NHFOV arms with a 1:1ratio, when patients fulfill all inclusion criteria. Randomization cannot be done earlier. Simple randomization will be done according to a computer-generated random number table and will be posted in a specific secured website 24/7 available. Twins will be allocated in the same treatment group. Infants randomized to one arm cannot crossover to the other or vice- versa during the study. For all the groups, if the fraction of inspired oxygen (FiO2) requirement is persistently higher than 0.30 per target SpO2 89-94% after starting the respiratory support, newborns receive Surfactant by LISA technique, administration of surfactant (Curosurf,Chiesi Pharmaceutics, Parma, Italy) 200 mg/kg. After the administration of surfactant, if FiO2 requirement is persistently >0.4 to keep SpO2 89-94% or severe apnea episodes are present (defined as recurrent apnea with >3 episodes/h associated with heart rate <100/min or a single episode of apnea requiring bag and mask ventilation within a 24-hour period ) or at the blood gas (arterial or free-flowing capillary blood) PaCO2>60 mmHg and potential of hydrogen (pH)<7.20 obtained at least 1 hour after commencement of the assigned treatment, newborns are intubated and mechanically ventilated. For all the newborns enrolled in the study, arterial or free-flowing capillary blood gas is checked every 6-12 hours, a cerebral and cardiac ultrasound screening is performed within 24 hrs. Further controls follow the routine of the ward.

Official Title
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NHFOV vs nCPAP in Very Preterm Infants With Respiratory Distress Syndrome: A Multi-center, Prospective, Randomized, Controlled Clinical Superior Trial

Conditions
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to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm Neonates

Intervention / Treatment
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* Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP
* Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Gestational age between 240/7 and 286/7 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and a fraction of inspired oxygen (FiO2) greater than 0.25 for target saturation of peripheral oxygen (SpO2) 89% to 94%；（3） Age less than 2 hours Exclusion Criteria: Intubated forany reasons at birth Major congenital malformations or known complex congenital heart disease No parental consent

Ages Eligible for Study
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Minimum Age: 0 Hours
Maximum Age: 2 Hours

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NCPAP<br> | Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP<br>* neonates assigned to the nCPAP group will be started on a pressure of 6 cmH2O( adjust range:6-10 cmH2O) , with FiO2 (0.21-0.40)adjusted to target SpO2 from 89% to 94%. CPAP will be provided by either variable flow or continuous flow devices, as there is no clear evidence that one type of CPAP generator would be better than any other by pure CPAP system.<br>Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV<br>* neonates assigned to NHFOV will be started with the following boundaries: a) Paw of 6 cmH2O (the range 6-10 cmH2O); b) frequency of 10 Hz (the range 8-12 Hz). c) Inspiratory time 50% (1:1). d) amplitude 15 cmH2O(the range 15-25 cmH2O) NHFOV will only be provided with piston/ membrane oscillators able to provide an active expiratory phase (that is, Acutronic FABIAN-III, SLE 5000, Loweinstein Med LEONI+, Sensormedics 3100A).<br>|
| Active Comparator: NHFOV<br> | Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP<br>* neonates assigned to the nCPAP group will be started on a pressure of 6 cmH2O( adjust range:6-10 cmH2O) , with FiO2 (0.21-0.40)adjusted to target SpO2 from 89% to 94%. CPAP will be provided by either variable flow or continuous flow devices, as there is no clear evidence that one type of CPAP generator would be better than any other by pure CPAP system.<br>Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV<br>* neonates assigned to NHFOV will be started with the following boundaries: a) Paw of 6 cmH2O (the range 6-10 cmH2O); b) frequency of 10 Hz (the range 8-12 Hz). c) Inspiratory time 50% (1:1). d) amplitude 15 cmH2O(the range 15-25 cmH2O) NHFOV will only be provided with piston/ membrane oscillators able to provide an active expiratory phase (that is, Acutronic FABIAN-III, SLE 5000, Loweinstein Med LEONI+, Sensormedics 3100A).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment failure within 72 hours after randomization 72 hours after randomization need for invasive mechanical ventilation |  | within 72 hrs from the beginning of the study mode | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of airleaks(pneumothorax and/or pneumomediastinum) occurred during noninvasive respiratory support | the diagnosis a Chest XR | the first 4weeks of life or until NICU discharge, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasal high frequency oscillation ventilation(NHFOV); nasal continuous positive airway pressure(NCPAP); preterm infants