High-Flow Nasal Cannula Versus Nasal CPAP as Primary Support in Preterm Respiratory Distress Syndrome

NCT07693530 | Completed DMC

• 1 other identifier: Ethics C.D.No:141(Kayseri CH)
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center randomized controlled trial compared heated humidified high-flow nasal cannula (HHHFNC) with nasal continuous positive airway pressure (nCPAP) as primary noninvasive respiratory support in preterm infants (gestational age 28-34 weeks; birth weight 1000-2000 g) with moderate respiratory distress syndrome. The primary outcome was treatment failure requiring invasive mechanical ventilation within the first 7 days.

Conditions

Premature Birth; Respiratory Distress Syndrome, Newborn

Keywords

HHHFNC; nCPAP; Preterm infant; Noninvasive respiratory support

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Failure Requiring Invasive Mechanical Ventilation

  Treatment failure defined as the need for invasive mechanical ventilation per pre-specified criteria (FiO2 \>=0.60 to maintain SpO2 91-95%; pH \<7.20 with PaCO2 \>60 mmHg; recurrent or caffeine-refractory apnea; markedly increased work of breathing; or clinical deterioration determined by the attending neonatologist), assessed at 72 hours, Day 5, and Day 7 of life.

  First 7 days of life (assessed at 72 hours, Day 5, and Day 7)

Secondary Outcomes (3)

• Number of Participants With Nasal Trauma

  During noninvasive respiratory support (first 7 days of life)

• Number of Participants With Proven (Culture-Positive) Late-Onset Sepsis

  From 72 hours of life through hospital discharge, an average of 24 days

• Number of Participants With Bronchopulmonary Dysplasia (BPD)

  At 36 weeks postmenstrual age

Other Outcomes (14)

• Number of Participants With Patent Ductus Arteriosus (PDA) Requiring Treatment

  From randomization through hospital discharge, an average of 24 days

• Number of Participants With Intraventricular Hemorrhage (IVH) of Any Grade

  From randomization through hospital discharge, an average of 24 days

• Number of Participants With Necrotizing Enterocolitis (NEC) of Any Stage

  From randomization through hospital discharge, an average of 24 days

Study Arms (2)

Group 1 Heated humidified high-flow nasal cannula (HHHFNC)

EXPERIMENTAL

n:43 Vapotherm Precision Flow Hi-VNI; initial flow 5 L/min (range 5-8 L/min), 37°C, 100% humidity; FiO₂ titrated to SpO₂ 91-95%.

Device: Group 1 Heated humidified high-flow nasal cannula (HHHFNC)

Group 2 Nasal continuous positive airway pressure (nCPAP)

ACTIVE COMPARATOR

n:43 nCPAP via ventilator-driven system; pressure 5-8 cmH2O; FiO2 titrated to SpO2 91-95%.

Device: Group 2 Nasal continuous positive airway pressure (nCPAP)

Interventions

Group 1 Heated humidified high-flow nasal cannula (HHHFNC) DEVICE

HHHFNC delivered via the Vapotherm Precision Flow Hi-VNI system; initial flow 5 L/min (range 5-8 L/min), 37°C, 100% humidity; FiO2 titrated to maintain SpO2 91-95%.

Also known as: Vapotherm Precision Flow Hi-VNI

Group 1 Heated humidified high-flow nasal cannula (HHHFNC)

Group 2 Nasal continuous positive airway pressure (nCPAP) DEVICE

nCPAP delivered via a ventilator-driven system; pressure 5-8 cmH2O; FiO2 titrated to maintain SpO2 91-95%.

Also known as: nCPAP

Group 2 Nasal continuous positive airway pressure (nCPAP)

Eligibility Criteria

• Age: 28 Weeks - 34 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants admitted to the NICU who fulfilled all of the following were eligible:
• Gestational age (GA) 28+0 to 34+6 weeks and/or birth weight 1,000-2,000 g
• Clinical and radiological diagnosis of moderate respiratory distress syndrome (RDS)
• Silverman-Anderson score (SAS) 4 \< SAS \< 7
• Eligibility for noninvasive ventilatory support

You may not qualify if:

• Parental refusal of consent
• Outborn infants transferred from other centers
• Infants who required immediate intubation in the delivery room
• Major congenital anomalies, chromosomal disorders, gastrointestinal malformations, or life-threatening congenital cardiac defects
• Nasal/pharyngeal anatomical anomalies (choanal atresia, cleft palate/lip)
• Moderate-to-severe hypoxic-ischemic encephalopathy (Grade 2-3)
• Infants who died unexpectedly shortly after admission without respiratory evaluation

Sponsors & Collaborators

• Kayseri City Hospital: lead

Study Sites (1)

Kayseri City Hospital

Kayseri, Kayseri, 38090, Turkey (Türkiye)

Location

Related Publications (10)

• Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3-23. doi: 10.1159/000528914. Epub 2023 Feb 15.

  PMID: 36863329 RESULT

• Hodgson KA, Wilkinson D, De Paoli AG, Manley BJ. Nasal high flow therapy for primary respiratory support in preterm infants. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006405. doi: 10.1002/14651858.CD006405.pub4.

  PMID: 37144837 RESULT

• Bruet S, Butin M, Dutheil F. Systematic review of high-flow nasal cannula versus continuous positive airway pressure for primary support in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2022 Jan;107(1):56-59. doi: 10.1136/archdischild-2020-321094. Epub 2021 May 20.

  PMID: 34016651 RESULT

• Luo K, Huang Y, Xiong T, Tang J. High-flow nasal cannula versus continuous positive airway pressure in primary respiratory support for preterm infants: A systematic review and meta-analysis. Front Pediatr. 2022 Nov 21;10:980024. doi: 10.3389/fped.2022.980024. eCollection 2022.

  PMID: 36479290 RESULT

• Aramesh MR, et al. nCPAP vs HFNC for RDS in preterm neonates: a RCT. Curr Respir Med Rev. 2025;21(3). doi:10.2174/011573398X339994241209170750

  RESULT

• Singh S, Ananthan A, Nanavati R. Post-INSURE Administration of Heated Humidified High-Flow Therapy Versus Nasal Continuous Positive Airway Pressure in Preterm Infants More Than 28 Weeks Gestation with Respiratory Distress Syndrome: A Randomized Non-Inferiority Trial. J Trop Pediatr. 2022 Jun 6;68(4):fmac062. doi: 10.1093/tropej/fmac062.

  PMID: 35877150 RESULT

• Demirel G, Vatansever B, Tastekin A. High Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure for Primary Respiratory Support in Preterm Infants: A Prospective Randomized Study. Am J Perinatol. 2021 Feb;38(3):237-241. doi: 10.1055/s-0039-1696673. Epub 2019 Sep 28.

  PMID: 31563133 RESULT

• Murki S, Singh J, Khant C, Kumar Dash S, Oleti TP, Joy P, Kabra NS. High-Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure for Primary Respiratory Support in Preterm Infants with Respiratory Distress: A Randomized Controlled Trial. Neonatology. 2018;113(3):235-241. doi: 10.1159/000484400. Epub 2018 Jan 23.

  PMID: 29393237 RESULT

• 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.

  PMID: 27532363 RESULT

• Roberts CT, Owen LS, Manley BJ, Froisland DH, Donath SM, Dalziel KM, Pritchard MA, Cartwright DW, Collins CL, Malhotra A, Davis PG; HIPSTER Trial Investigators. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. N Engl J Med. 2016 Sep 22;375(12):1142-51. doi: 10.1056/NEJMoa1603694.

  PMID: 27653564 RESULT

MeSH Terms

Conditions

Premature Birth; Respiratory Distress Syndrome, Newborn

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Respiratory Distress Syndrome; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: July 9, 2026
• Study Start: June 1, 2020
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: July 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)