NHFOV vs. NCPAP as a Primary Treatment to Neonatal Respiratory Distress Syndrome(NRDS)

Study Overview
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Brief Summary
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The investigators compared advantages and disadvantages of two forms of noninvasive respiratory support -noninvasive high-frequency oscillatory ventilation (nHFOV) or nasal continuous positive airway pressure (nCPAP) -as a primary mode of ventilation in premature infants with RDS．

Detailed Description
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Background: Invasive mechanical ventilation is associated with development of adverse pulmonary and non-pulmonary outcomes in very low birth weight infants. Various modes of non-invasive respiratory support are being increasingly used to minimize the incidence of bronchopulmonary dysplasia (BPD). The aim of this trials to compare the effect of noninvasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary noninvasive ventilation support mode. Methods/Design:In this multicenter, randomized, controlled trial, 300 preterm infants at gestational age (GA) less than 34 weeks with a diagnosis of RDS will be randomized to NHFOV or NCPAP as a primary mode of non-invasive respiratory support. Study will be conducted in 18 tertiary neonatal intensive care units in China. The primary outcome is the need for invasive mechanical ventilation (IMV)during the first 7 days after enrollment in preterm infants randomized to the two groups. The secondary outcomes include days of hospitalization, days on noninvasive respiratory support, days on IMV, days on supplemental oxygen, mortality, need for surfactant, incidence of retinopathy of prematurity(ROP) and bronchopulmonary dysplasia(BPD), occurrence of abdominal distention, air leaks, intraventricular hemorrhage (IVH ≥ grade 3) and necrotizing enterocolitis (NEC> II stage). Other secondary outcomes include scores of Bayley Scales of Infant Development at 2 months and 2 years of corrected age.

Official Title
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Noninvasive Ventilation for Preterm Neonates With Respiratory Distress Syndrome: a Multi-center Randomized Controlled Trial

Conditions
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Preterm Infants

Intervention / Treatment
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* Procedure: noninvasive high-frequency ventilation (nHFOV)
* Procedure: nasal continuous positive airway pressure (nCPAP)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: (1)Gestational age (GA) is from 26 to 34 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and chest X-ray findings; (3) RDS Silverman score>5; (4) informed parental consent has been obtained. Exclusion criteria (1) severe RDS requiring early intubation according to the American Academy of Pediatrics guidelines for neonatal resuscitation7; (2)major congenital malformations or complex congenital heart disease; (3) group B hemolytic streptococcus pneumonia, septicemia, pneumothorax, pulmonary hemorrhage; (4) cardiopulmonary arrest needing prolonged resuscitation; (5) transferred out of the NICUs without treatment.

Ages Eligible for Study
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Maximum Age: 12 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>nasal continuous positive airway pressure (nCPAP) - as a primary mode of ventilation in premature infants with RDS | Procedure: nasal continuous positive airway pressure (nCPAP)<br>* Infants assigned to the NCPAP group will be started on a pressure of 6 cmH2O (range: 6-8 cmH2O) by CPAP system (CNO Medin, Germany, Carefusion, USA)<br>|
| Experimental: nHFOV<br>noninvasive high-frequency ventilation (nHFOV) as a primary mode of ventilation in premature infants with RDS | Procedure: noninvasive high-frequency ventilation (nHFOV)<br>* NHFOV will be provided by a high frequency ventilator (CNO, Medin, Germany or SLE 5000, UK). NHFOV will be provided via binasal prongs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Required Intubation | The criteria for endotracheal mechanical ventilation were as follows: severe respiratory acidosis (PaCO2 > 60 mmHg with pH<7.20), severe apnea and bradycardia (defined as recurrent apnea with > 3 episodes per hour associated with heart rate < 100/min, a single episode of apnea that required bag and mask ventilation), hypoxia (FiO2>0.5 with PaO2<50mmHg), severe respiratory distress, neonatal pulmonary hemorrhage, and cardiopulmonary arrest without effective resuscitation needing continued ventilation and rescue | during the first 7 days after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Incidence of Intraventricular Hemorrhage (IVH, ≥ Grade Ⅲ) | The criteria for intraventricular hemorrhage (IVH, ≥ grade Ⅲ): intraventricular hemorrhage with ventricular dilatation and intraventricular hemorrhage with paren- ehymal hemorrhage. Intraventricular hemorrhage (≥ grade Ⅲ) is worse outcome. | first two months after birth | 
| the Incidence of Pneumothorax | the incidence of pneumothorax | during non-invasive ventilation, up to 7 days | 
| the Incidence of Neonatal Necrotizing Enterocolitis(>Stage II) | The criteria for neonatal necrotizing enterocolitis(>stage II): Unequivocal malfunction of the gastrointestinal tract is demonstrated clinically and by radiographic evaluation. Other disorders such as malrotation and volvulus and Hirschsprung's disease must be excluded. Neonatal necrotizing enterocolitis(>stage II) is worse outcome | during non-invasive ventilation, up to 7 days | 
| the Incidence of Retinopathy of Prematurity (>Stage II) | The criteria for Retinopathy of prematurity (>Stage II); extraretinal fibrovascular proliferation neovascularization extends from ridge into the vitreous. Retinopathy of prematurity (>Stage II) is worse outcome. | at a post-menstrual age of 36 weeks or at discharge | 
| The Score of Bayley Scales of Infant Development | scores of Bayley Scales of Infant Development at 2 months old and 2 years old | 30 months | 
| the Incidence of Bronchopulmonary Dysplasia(BPD) | BPD was defined according to the National Institutes of Health consensus definition: Need for O2 supplementation(FiO2>0.21) for at least 28 days after birth. BPD is worse outcome. | at a post-menstrual age of 36 weeks or at discharge | 
| the Incidence of Abdominal Distention | Abdominal circumference increase 2 centimeter during non-invasive ventilation | during non-invasive ventilation, up to 7 days | 
| The Time of Non-invasive Ventilation | Hours | during non-invasive ventilation, up to 30 days | 
| Length of Hospitalization | Days | during hospitalization, up to 60 days | 
| Predischarge Mortality |  | during hospitalization, up to 60 days | 
| Length of O2 Therapy | Days | during hospitalization, up to 60 days | 
| Number of Participants With Thick Secretions Causing an Airway Obstruction | determined by the clinician | during non-invasive ventilation, up to 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NRDS, nHFOV, nCPAP, preterm infants