Clinical trial NCT02570217: HHHFNC (Heated Humidified High-Flow Nasal Cannula) Versus NCPAP for Respiratory Distress Syndrome of Prematurity
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Newborn Respiratory Distress Syndrome
Keywords: NCPAP, High Flow Nasal Cannula, pretem infants, NICU
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: Dr Anna Lavizzari
name: Dr Francesca Gaia Ciuffini
First posted: 2015-10-07
Enrollment: 316
Sex: ALL
Minimum age (years): 29
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Inborn
* Parental Consent

Exclusion Criteria:

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

Primary outcomes:
measure: number of patients needing intubation and mechanical ventilation within 72 hrs from the beginning of the study mode
timeFrame: within 72 hrs from the beginning of the study mode
Secondary outcomes:
measure: overall duration of respiratory assistance
timeFrame: up to 2 years from birth
measure: overall duration of oxygen requirement
timeFrame: up to 2 years from birth
measure: overall duration of non invasive respiratory assistance
timeFrame: up to 2 years from birth
measure: Surfactant treatment
timeFrame: through study completion, an average of 1 year
measure: full enteral feeding
timeFrame: through study completion, an average of 1 year
measure: overall duration of hospitalisation
timeFrame: up to 2 years from birth
measure: air-leak syndrome
timeFrame: through study completion, an average of 1 year
measure: Intra ventricular Hemorrage
timeFrame: through study completion, an average of 1 year
measure: Patent Doctus Arterious
timeFrame: through study completion, an average of 1 year
measure: Infections
timeFrame: through study completion, an average of 1 year
measure: Necrotising Enterocolites (NEC)
timeFrame: through study completion, an average of 1 year
measure: Bronchopulmonary Dysplasia
timeFrame: up to 2 years from birth
measure: Retinopathy of Prematurity
timeFrame: through study completion, an average of 1 year
measure: overall mortality
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Milan
country: Italy
facility: NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
Study officials:
affiliation: IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
name: Mariarosa Colnaghi, MD
role: STUDY_DIRECTOR
References:
citation: 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.