Comparing of High Flow Nasal Cannula Versus Cpap for Initial Respiratory Stabilisation of Very Premature Infants

NCT06543589 | Not Yet Recruiting DMC

• 1 other identifier: 8/24
• Study Type: interventional
• Target: 443
• Locations: 0 countries
• Sites: N/A

Brief Summary

Non-invasive continuous positive airway pressure (CPAP) stabilizes premature newborns, but its optimal pressure is unknown. High-flow nasal cannula (HFNC) is an alternative that minimizes trigeminal stimulation but lacks precise pressure control. Initial studies show HFNC's feasibility and effectiveness. This study hypothesizes that HFNC can deliver adequate pressure, reduce the need for positive pressure ventilation, and support safe stabilization of very premature infants. The trial compares the effectiveness and safety of HFNC versus CPAP in the delivery room and during transport to the neonatal intensive care unit in very premature infants. The primary objective is to compare HFNC and CPAP in reducing the need for positive pressure ventilation in very premature infants immediately after birth. The study includes very premature infants delivered between 28+0 and 31+6 weeks gestation in 10 tertiary referral centers (nine in the Czech Republic, one in Slovakia). Approximately 443 patients are required to detect a 15% relative decrease in the need for positive pressure ventilation between trial groups. Centers will be randomized to either CPAP or HFNC at each time period, with parental consent obtained before birth. The primary endpoint is the proportion of neonates requiring positive pressure ventilation within the first 10 minutes post-birth.

Conditions

Premature; Infant

Outcome Measures

Primary Outcomes (1)

• Positive pressure ventilation (PPV)

  The primary endpoint of the trial is to demonstrate a difference in the proportion of neonates requiring PPV administration in the delivery room during the first 10 minutes post-birth. This will be recorded as a binary outcome (yes/no) indicating whether PPV was administered. Each neonate's need for PPV should be documented by the clinical team and recorded in a standardized data collection form immediately after delivery.

  10 minutes after delivery

Secondary Outcomes (3)

• SpO2 >80% within the first 5 minutes of life

  5 minutes after delivery

• SpO2 >90% with FiO2 ≤ 0.40 within the first 10 minutes of life

  10 minutes after delivery

• Stabilization on selected ventilatory support

  3 hours after delivery

Study Arms (2)

ARM A (CPAP group)

NO INTERVENTION

Infants randomized to the ARM A group will be stabilized on CPAP, according to the standard procedure of each participating center.

ARM B (HFNC group)

EXPERIMENTAL

For infants randomly assigned to the ARM B group, the respiratory support will be provided by devices that deliver a blend of heated and humidified gas mixture of air and oxygen at gas flows exceeding 8 L/ min via binasal cannula.

Device: High-flow-nasal-cannula

Interventions

High-flow-nasal-cannula DEVICE

Respiratory support will be provided by devices that deliver a blend of heated and humidified gas mixture of air and oxygen at gas flows exceeding 8 L/ min via binasal cannula.

ARM B (HFNC group)

Eligibility Criteria

• Age: 1 Minute - 5 Minutes
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age at birth between 28+0 and 31+6 weeks by the best obstetric estimate.
• Written informed consent from parent/legal guardian(s) is obtained before delivery.

You may not qualify if:

• Peripartal hypoxia with pH \< 7,1
• Significant congenital malformations.
• IUGR with estimated weight of fetus below 800g.
• Condition that has an adverse effect on breathing/ventilation or oxygenation, including congenital diaphragmatic hernia, trachea-oesophageal fistula, cyanotic heart disease and surfactant protein deficiency.
• Documented decision to give palliative neonatal care.

Sponsors & Collaborators

• Charles University, Czech Republic: lead

Related Publications (13)

• Madar J, Roehr CC, Ainsworth S, Ersdal H, Morley C, Rudiger M, Skare C, Szczapa T, Te Pas A, Trevisanuto D, Urlesberger B, Wilkinson D, Wyllie JP. European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth. Resuscitation. 2021 Apr;161:291-326. doi: 10.1016/j.resuscitation.2021.02.014. Epub 2021 Mar 24.

  PMID: 33773829 BACKGROUND

• Kirpalani H, Ratcliffe SJ, Keszler M, Davis PG, Foglia EE, Te Pas A, Fernando M, Chaudhary A, Localio R, van Kaam AH, Onland W, Owen LS, Schmolzer GM, Katheria A, Hummler H, Lista G, Abbasi S, Klotz D, Simma B, Nadkarni V, Poulain FR, Donn SM, Kim HS, Park WS, Cadet C, Kong JY, Smith A, Guillen U, Liley HG, Hopper AO, Tamura M; SAIL Site Investigators. Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial. JAMA. 2019 Mar 26;321(12):1165-1175. doi: 10.1001/jama.2019.1660.

  PMID: 30912836 BACKGROUND

• Lista G, Cavigioli F, La Verde PA, Castoldi F, Bresesti I, Morley CJ. Effects of Breathing and Apnoea during Sustained Inflations in Resuscitation of Preterm Infants. Neonatology. 2017;111(4):360-366. doi: 10.1159/000454799. Epub 2017 Jan 25.

  PMID: 28118641 BACKGROUND

• Martherus T, Oberthuer A, Dekker J, Hooper SB, McGillick EV, Kribs A, Te Pas AB. Supporting breathing of preterm infants at birth: a narrative review. Arch Dis Child Fetal Neonatal Ed. 2019 Jan;104(1):F102-F107. doi: 10.1136/archdischild-2018-314898. Epub 2018 Jul 26.

  PMID: 30049727 BACKGROUND

• Kuypers K, Martherus T, Lamberska T, Dekker J, Hooper SB, Te Pas AB. Reflexes that impact spontaneous breathing of preterm infants at birth: a narrative review. Arch Dis Child Fetal Neonatal Ed. 2020 Nov;105(6):675-679. doi: 10.1136/archdischild-2020-318915. Epub 2020 Apr 29.

  PMID: 32350064 BACKGROUND

• Kuypers KLAM, Hopman A, Cramer SJE, Dekker J, Visser R, Hooper SB, Te Pas AB. Effect of initial and subsequent mask applications on breathing and heart rate in preterm infants at birth. Arch Dis Child Fetal Neonatal Ed. 2023 Nov;108(6):594-598. doi: 10.1136/archdischild-2022-324835. Epub 2023 Apr 20.

  PMID: 37080734 BACKGROUND

• Reynolds P, Leontiadi S, Lawson T, Otunla T, Ejiwumi O, Holland N. Stabilisation of premature infants in the delivery room with nasal high flow. Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101(4):F284-7. doi: 10.1136/archdischild-2015-309442. Epub 2016 Jan 5.

  PMID: 26733541 BACKGROUND

• Siva NV, Reynolds PR. Stabilisation of the preterm infant in the delivery room using nasal high flow: A 5-year retrospective analysis. Acta Paediatr. 2021 Jul;110(7):2065-2071. doi: 10.1111/apa.15824. Epub 2021 Mar 8.

  PMID: 33638878 BACKGROUND

• Roberts CT, Hodgson KA. Nasal high flow treatment in preterm infants. Matern Health Neonatol Perinatol. 2017 Sep 6;3:15. doi: 10.1186/s40748-017-0056-y. eCollection 2017.

  PMID: 28904810 BACKGROUND

• Mazmanyan P, Darakchyan M, Pinkham MI, Tatkov S. Mechanisms of nasal high flow therapy in newborns. J Appl Physiol (1985). 2020 Apr 1;128(4):822-829. doi: 10.1152/japplphysiol.00871.2019. Epub 2020 Feb 20.

  PMID: 32078463 BACKGROUND

• Bjorland PA, Oymar K, Ersdal HL, Rettedal SI. Incidence of newborn resuscitative interventions at birth and short-term outcomes: a regional population-based study. BMJ Paediatr Open. 2019 Dec 29;3(1):e000592. doi: 10.1136/bmjpo-2019-000592. eCollection 2019.

  PMID: 31909225 BACKGROUND

• 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 BACKGROUND

• Manley BJ, Arnolda GRB, Wright IMR, Owen LS, Foster JP, Huang L, Roberts CT, Clark TL, Fan WQ, Fang AYW, Marshall IR, Pszczola RJ, Davis PG, Buckmaster AG; HUNTER Trial Investigators. Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries. N Engl J Med. 2019 May 23;380(21):2031-2040. doi: 10.1056/NEJMoa1812077.

  PMID: 31116919 BACKGROUND

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Central Study Contacts

Tereza Lamberska, PhD

CONTACT

+4202249674444; tereza.lamberska@vfn.cz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Model Details: The randomization unit in this study is the center, rather than individual patients. Centers will be randomized to either the ARM A or ARM B at each time period using a stepped-wedge cluster-randomized design. A randomization schedule will be generated using a computer-based random number generator to ensure unbiased allocation. At each of the specified time periods, a random subset of centers will be selected to switch from control to intervention. While it is not feasible to blind the centers to their intervention status due to the nature of the study, the data analysts will be blinded to the group assignments to minimize bias. The randomization will be implemented by the study coordinator, who will notify each center of their assignment at the beginning of each time period. This approach ensures that each center will eventually receive the intervention, allowing for both within-center and between-center comparisons, thus enhancing the robustness of the study findings.

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 9, 2024
• Study Start: December 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share