Clinical trial NCT06543589: Comparing of High Flow Nasal Cannula Versus Cpap for Initial Respiratory Stabilisation of Very Premature Infants
Official title: A Randomised Trial Comparing of High Flow Nasal Cannula Versus Cpap for Initial Respiratory Stabilisation of Very Premature Infants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Premature; Infant
Lead sponsor: Charles University, Czech Republic
Sponsor class: OTHER
First posted: 2024-08-09
Enrollment: 443
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Positive pressure ventilation (PPV)
timeFrame: 10 minutes after delivery
Secondary outcomes:
measure: SpO2 >80% within the first 5 minutes of life
timeFrame: 5 minutes after delivery
measure: SpO2 >90% with FiO2 ≤ 0.40 within the first 10 minutes of life
timeFrame: 10 minutes after delivery
measure: Stabilization on selected ventilatory support
timeFrame: 3 hours after delivery
Other outcomes:
Locations:
Study officials:
References:
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