Comparing of High Flow Nasal Cannula Versus Cpap for Initial Respiratory Stabilisation of Very Premature Infants (SIMPLSAFE3)

November 8, 2024 updated by: Jonáš Klára, Charles University, Czech Republic

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background and Rationale

The stabilization of very premature infants (VPIs) immediately after birth is crucial, as their underdeveloped lungs are prone to respiratory distress. Non-invasive continuous positive airway pressure (CPAP) is commonly recommended in the delivery room and during transport to the NICU. While CPAP can help maintain airway pressure and support spontaneous breathing, its optimal pressure settings are not yet established. Furthermore, when CPAP pressure is increased for infants who are not breathing spontaneously, it often necessitates positive pressure ventilation (PPV), which may lead to lung injury and increase the risk of complications.

CPAP's reliance on a face mask requires frequent adjustments, which can trigger reflexes that may exacerbate bradycardia, potentially destabilizing the neonate. High-flow nasal cannula (HFNC) offers an alternative that reduces direct facial stimulation, thus potentially lowering the occurrence of these reflex-induced events. Preliminary studies suggest that HFNC is both feasible and effective in supporting some premature infants, though HFNC does not provide the precise pressure control seen with CPAP. This study is designed to evaluate if HFNC can provide effective airway pressure for initial lung clearance, decrease the need for PPV, and support safe respiratory stabilization of VPIs immediately after birth.

Hypothesis

HFNC will reduce upper airway resistance and deliver adequate positive pressure for lung aeration in spontaneously breathing, very immature neonates. Compared to CPAP, HFNC's reduced physical stimulation may decrease the requirement for PPV, promoting a smoother transition to stable lung function and cardiopulmonary stabilization in very preterm infants.

Trial Aim

This trial aims to compare the effectiveness and safety of HFNC and CPAP in stabilizing severely premature neonates in the delivery room and during transport to the NICU. The primary endpoint is the proportion of neonates requiring PPV within the first 10 minutes post-birth, to determine if HFNC can reduce the need for PPV more effectively than CPAP.

Objectives

The primary objective is to evaluate whether HFNC can reduce the need for PPV compared to CPAP in very premature infants immediately after birth. Secondary objectives will focus on achieving specific oxygenation and ventilation milestones without PPV, including SpO₂ levels and FiO₂ requirements.

Study Design

This is a stepped-wedge cluster randomized controlled trial (RCT) involving 10 tertiary perinatal care centers (9 in the Czech Republic, 1 in Slovakia). Participating centers will switch between using HFNC and CPAP during specified time periods. Randomization will determine the order in which each center uses either HFNC or CPAP across six to ten periods of approximately 90 days each.

Study Type

Interventional

Enrollment (Estimated)

443

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: ARM A (CPAP group)
Infants randomized to the ARM A group will be stabilized on CPAP, according to the standard procedure of each participating center.
Experimental: ARM B (HFNC group)
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive pressure ventilation (PPV)
Time Frame: 10 minutes after delivery

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
SpO2 >80% within the first 5 minutes of life
Time Frame: 5 minutes after delivery

Achieving SpO2 >80% within the first 5 minutes of life, regardless of FiO2 without the need of PPV administration.

Oxygen saturation (SpO₂) will be measured continuously using a pulse oximeter attached to the infant.
5 minutes after delivery
SpO2 >90% with FiO2 ≤ 0.40 within the first 10 minutes of life
Time Frame: 10 minutes after delivery

Achieving SpO2 >90% with FiO2 ≤ 0.40 within the first 10 minutes of life without the need for PPV.

Oxygen saturation (SpO₂) will be measured continuously using a pulse oximeter attached to the infant.
10 minutes after delivery
Stabilization on selected ventilatory support
Time Frame: 3 hours after delivery

Stabilization on selected ventilatory support with FiO2 ≤ 0.35 without the use of PPV at 3h of life.

FiO₂ and respiratory support (CPAP or HFNC) will be documented.
3 hours after delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charles University, Czech Republic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

August 5, 2024

First Submitted That Met QC Criteria

August 5, 2024

First Posted (Actual)

August 9, 2024

Study Record Updates

Last Update Posted (Estimated)

November 12, 2024

Last Update Submitted That Met QC Criteria

November 8, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8/24

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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