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

Charles University, Czech Republic

Status: Not yet enrolling

Conditions: Premature; Infant

Treatments: Device: High-flow-nasal-cannula

Study type: Interventional

Funder types: Other

Identifiers

NCT06543589

8/24

Details and patient eligibility

About

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.

Full 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.

Enrollment: 443 estimated patients

Sex: All

Ages: 1 to 5 minutes old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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443 participants in 2 patient groups

ARM A (CPAP group)

No Intervention group

Description:

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 group

Description:

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.

Treatment:

Device: High-flow-nasal-cannula