HHHFNC (Heated Humidified High-Flow Nasal Cannula) Versus NCPAP for Respiratory Distress Syndrome of Prematurity

Study Overview
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Brief Summary
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Preterm infants ranging from 29+0 to 36+6 weeks+days are randomly assigned to one of the following treatments as non invasive respiratory support if they develop mild to moderate Respiratory Distress Syndrome within 72 hrs from birth: 1) NCPAP set at 4-6 cmH2O or 2) HHHFNC providing a flow 4-6 l/min. The aim of the study is to assess efficacy and safety of relative new form of respiratory support (HHHFNC) versus a more common one (NCPAP).

Detailed Description
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Preterm infants are eligible to the study if they present mild to moderate Respiratory Distress Syndrome (RDS) defined by the following criteria: need of FiO2 ( Fraction of Inspired Oxygen) ≥0.30 to keep a target SpO2 (Periferal Oxygen Saturation) beetween 88-93% and/or Silverman score ≥5. To confirm the diagnosis a Chest XR is performed as routinarily in the ward before starting the respiratory support. They are randomly assigned to one of the treatment groups cited in brief summary by means of closed envelops. A block randomization is applided with a blok size of 4. The randomization is stratified per groups accoring to gestational age: from 29+0 to 32+6; from 33+0 to 34+6; from 35+0 to 36+6 weeks+days. Once the treatment is started, for the group NCPAP there is the possibility to switch to the mode Bi-PAP if: there are more than 4 episodes of apnoea per hour or more than 2 episodes requiring positive pressure ventilation or if deemed by clinicians for increased work of breathing assesed by the Silverman score. For all the groups, if the FiO2 requirement is persistently higher than 0.35-0.40 per target SpO2 86-93% and/or dyspnoea defined by Silverman score > 6 after starting the respiratory support, newborns receive Surfactant by INSURE technique, involving endotracheal intubation by direct laryngoscopic vision, endotracheal administration of surfactant (Curosurf, Chiesi Pharmaceutics, Parma, Italy) 200 mg/kg and finally extubation. After the administration of surfactant, if FiO2 requirement is persistently >0.4 to keep SpO2 86-93% or severe apnea episodes are present (apnea episodes > 4/hr or >2/hr requiring positive pressure ventilation) or at the blood gas (capillary or venous) PaCO2>70 mmHg and pH<7.20, newborns are intubated and mechanically ventilated. For all the newborns enrolled in the study, capillary or venous 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. Weaning is started decreasing HHHFNC flow by 1 lpm or nCPAP pressure by 1 cmH2O pressure if infants are presenting FIO2 < 0.30 to target SpO2 and minimal or no signs of respiratory effort. The respiratory support is discontinued for flow ≤ 2 lpm or pressure ≤ 2 cmH2O.

Official Title
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HHHFNC (Heated Humidified High-Flow Nasal Cannula) Versus NCPAP (Nasal Continuous Positive Airway Pressure) in Preterm Infants With Mild to Moderate Respiratory Distress Syndrome (RDS): a Randomized Clinical Trial.

Conditions
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Newborn Respiratory Distress Syndrome

Intervention / Treatment
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* Device: HHHFNC
* Device: NCPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inborn Parental Consent Exclusion Criteria: No parental consent Major congenital malformations Severe intra ventricular hemorrage diagnosed early after birth

Ages Eligible for Study
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Minimum Age: 29 Weeks
Maximum Age: 36 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HHHFNC<br>The patients receive respiratory support by mean of Heated Humidified High Flow Nasal cannula | Device: HHHFNC<br>* infants receive non-invasive respiratory support by mean of HHHFNC<br>* Other names: PRECISION FLOW (Vapotherm,Stevensville, USA);|
| Active Comparator: NCPAP<br>Patients receive respiratory support by Nasal Continuous Positive Airways Pressure(NCPAP) | Device: NCPAP<br>* infants receive non-invasive respiratory support by mean of NCPAP<br>* Other names: SiPAP (Viasys Healthcare, Palm Springs, CA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients needing intubation and mechanical ventilation within 72 hrs from the beginning of the study mode | The procedure defined as INSURE and described in details in the section Detailed Study Description is not considered as a failure for the primary outcome. | within 72 hrs from the beginning of the study mode | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall duration of respiratory assistance | respiratory assistance includes both invasive and non invasive respiratory supports | up to 2 years from birth | 
| overall duration of oxygen requirement | Apart from invasive and non invasive respiratory supports, for this specific outcome are considered also the days of oxygen administration by devices other then ventilators or HHHFNC devices. | up to 2 years from birth | 
| overall duration of non invasive respiratory assistance | If later during the hospitalisation the newborn receive non invasive ventilation, even if for different reasons from the beginning and/or by mean of a different mode or device, this is registered and computed as overall non invasive ventilation. | up to 2 years from birth | 
| Surfactant treatment | the overall number of doses of surfactant are considered | through study completion, an average of 1 year | 
| full enteral feeding | Number of days required to reach the  full enteral feeding (defined by a fluids intake about 120 ml/kg/day by enteral administration) | through study completion, an average of 1 year | 
| overall duration of hospitalisation |  | up to 2 years from birth | 
| air-leak syndrome |  | through study completion, an average of 1 year | 
| Intra ventricular Hemorrage |  | through study completion, an average of 1 year | 
| Patent Doctus Arterious | If a pharmaceutical or surgical treatment is required is considered. Small doctuses closing spontaneously during the first days of life are not included. | through study completion, an average of 1 year | 
| Infections | Sepsis, pneumonia, cellulites and other infections are considered | through study completion, an average of 1 year | 
| Necrotising Enterocolites (NEC) |  | through study completion, an average of 1 year | 
| Bronchopulmonary Dysplasia | Jobe-Bancalari classification criteria are applied. | up to 2 years from birth | 
| Retinopathy of Prematurity |  | through study completion, an average of 1 year | 
| overall mortality |  | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NCPAP, High Flow Nasal Cannula, pretem infants, NICU