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

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.

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).

Study Overview

• Status: Completed
• Conditions: Newborn Respiratory Distress Syndrome
• Intervention / Treatment: Device: HHHFNC; Device: NCPAP

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 316
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20122
    • NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inborn
• Parental Consent

Exclusion Criteria:

• No parental consent
• Major congenital malformations
• Severe intra ventricular hemorrage diagnosed early after birth

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HHHFNC; The patients receive respiratory support by mean of Heated Humidified High Flow Nasal cannula	Device: HHHFNC; infants receive non-invasive respiratory support by mean of HHHFNC; Other Names: PRECISION FLOW (Vapotherm,Stevensville, USA)
Active Comparator: NCPAP; Patients receive respiratory support by Nasal Continuous Positive Airways Pressure(NCPAP)	Device: NCPAP; infants receive non-invasive respiratory support by mean of NCPAP; Other Names: Infant Flow Driver System (EME Ltd, Brighton, Sussex, UK); SiPAP (Viasys Healthcare, Palm Springs, CA)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Collaborators: Dr Anna Lavizzari; Dr Francesca Gaia Ciuffini
• Investigators: Study Director: Mariarosa Colnaghi, MD, IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy

Publications and helpful links

General Publications

• Lavizzari A, Colnaghi M, Ciuffini F, Veneroni C, Musumeci S, Cortinovis I, Mosca F. Heated, Humidified High-Flow Nasal Cannula vs Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome of Prematurity: A Randomized Clinical Noninferiority Trial. JAMA Pediatr. 2016 Aug 8. doi: 10.1001/jamapediatrics.2016.1243. Online ahead of print.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: October 3, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (Estimate): October 7, 2015

Study Record Updates

• Last Update Posted (Estimate): October 7, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: NCPAP, High Flow Nasal Cannula, pretem infants, NICU
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hyaline Membrane Disease
• Other Study ID Numbers: HHHFNC vs NCPAP 2012; IRCCSMaggioreH (Other Identifier: IRCCSMaggioreH)