Surfactant Nebulization for the Early Aeration of the Preterm Lung

Study Overview
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Brief Summary
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Respiratory distress syndrome is the most common cause of respiratory failure in preterm infants. Treatment consists of respiratory support and exogenous surfactant administration. Commonly, surfactant is administered via an endotracheal tube during mechanical ventilation. However, mechanical ventilation is considered an important risk factor for developing bronchopulmonary dysplasia. Surfactant nebulisation during noninvasive ventilation may offer an alternative method for surfactant administration and has been shown to be promising in terms of physiological as well as clinical changes. In preterm infants with respiratory distress syndrome, the effect of intratracheally administered surfactant on lung function during invasive ventilation has been studied extensively. However, the effect of early postnatal surfactant nebulization remains unclear. Therefore, the investigators plan to conduct a randomized controlled trial in order to investigate the effect of surfactant nebulization immediately after birth on early postnatal lung volume and short-term respiratory stability.

Official Title
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Surfactant Nebulization for the Early Aeration of the Preterm Lung: a Single Blinded, Parallel, Randomized Controlled Trial

Conditions
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Preterm Birth, Respiratory Distress Syndrome, Surfactant Deficiency Syndrome Neonatal

Intervention / Treatment
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* Drug: Surfactant nebulisation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: inborn gestational age at birth from 26 0/7 to 31 6/7 weeks written informed consent Exclusion Criteria: severe congenital malformation adversely affecting surfactant nebulisation or life expectancy a priori palliative care genetically defined syndrome

Ages Eligible for Study
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Maximum Age: 3 Minutes

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surfactant nebulisation<br>The experimental group will receive a positive end-expiratory pressure (PEEP, +/- noninvasive positive pressure ventilation) and nebulised surfactant via a customised vibrating membrane nebuliser. Nebulisation will commence with the first application of a PEEP and will continue for a maximum of 30 minutes. | Drug: Surfactant nebulisation<br>* 200 mg/kg body weight nebulised surfactant (Poractant alfa, Chiesi Farmaceutici SpA, Parma, Italy) via a customised vibrating membrane nebuliser (eFlow neonatal nebuliser system, PARI Pharma, Starnberg).<br>|
| No Intervention: Standard care<br>The control group will receive standard care (PEEP, +/- noninvasive positive pressure ventilation, without surfactant nebulisation). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EIT: End-expiratory lung impedance (EELI) | Change in EELI using electrical impedance tomography (arbitrary units per kilogram) | Between birth and 30 minutes of life. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EIT: End-expiratory lung impedance (EELI) | EELI using electrical impedance tomography (arbitrary units per kilogram). | At 6, 12, and 24 hours of life and at 36 weeks postmenstrual age | 
| EIT: Regional ventilation distribution | Regional ventilation distribution using electrical impedance tomography (arbitrary units per kilogram). | At 6, 12, and 24 hours of life and at 36 weeks postmenstrual age. | 
| EIT: Tidal volumes | Tidal volumes using electrical impedance tomography (arbitrary units per kilogram). | At 6, 12, and 24 hours of life and at 36 weeks postmenstrual age. | 
| EIT: Association between EELI losses and SpO2/FiO2 ratio. | Association between the number of EELI losses >50% and the SpO2/FiO2 ratio. | At 6, 12, and 24 hours of life. | 
| EIT: Association between EELI losses and need/level of respiratory support. | Association between the number of EELI losses >50% and the need/level of respiratory support. | At 6, 12, and 24 hours of life. | 
| Physiological: Heart rate | Continuous recording of heart rate (beats per minute). | For the first 30 minutes after birth, as well as at 6, 12, and 24 hours of life. | 
| Physiological: Oxygen saturation (SpO2) | Continuous recording of SpO2 (%). | For the first 30 minutes after birth, and at 6, 12, and 24 hours of life. | 
| Physiological: Fraction of inspired oxygen | Continuous recording of fraction of inspired oxygen. | For the first 30 minutes after birth, and at 6, 12, and 24 hours of life. | 
| Physiological: SpO2/FiO2 ratio | SpO2/FiO2 ratio. | At 6, 12, and 24 hours of life. | 
| Physiological: Body temperature | Number of events with body temperature <36.5 or >37.5°C. | In the delivery room. | 
| Respiratory: Peak inspiratory pressure (PIP) | Continuous recording of PIP in the control group (cmH2O). | During the first 30 minutes of life. | 
| Respiratory: Positive end-expiratory pressure (PEEP) | Continuous recording of PEEP in the control group (cmH2O). | During the first 30 minutes of life. | 
| Respiratory: Tidal volume (Vt) | Continuous recording of Vt in the control group (cmH2O). | During the first 30 minutes of life. | 
| Respiratory: PEEP (positive end-expiratory pressure) | PEEP during noninvasive and invasive ventilation [mbar] | At 6, 12, and 24 hours of life. | 
| Respiratory: PIP (peak inspiratory pressure) | PIP during noninvasive and invasive ventilation [mbar] | At 6, 12, and 24 hours of life. | 
| Respiratory: Respiratory rate | Respiratory rate during noninvasive and invasive ventilation [breaths per minute] | At 6, 12, and 24 hours of life. | 
| Clinical: Length and type of noninvasive respiratory support | Total length of CPAP/NIPPV support assessed retrospectively using video recordings (min) | During the first 30 minutes of life. | 
| Clinical: Total time on noninvasive and invasive respiratory support | Total time on invasive and noninvasive respiratory support (days) | Until 36 weeks postmenstrual age | 
| Clinical: Frequency and duration of facemask repositioning | Frequency and duration of facemask repositioning assessed retrospectively using video recordings. | During the first 30 minutes after birth. | 
| Clinical: Intubation | Intubation rate (%) | At 24 and 72 hours of life, at 7 days of life. Until 36 weeks postmenstrual age. | 
| Clinical: Time to first intubation | Time to first intubation (days, minutes) | From birth until 36 weeks postmenstrual age. | 
| Clinical: Number of episodes of desaturation and bradycardia | Number of episodes of desaturation (SpO2 <80%) and bradycardia (<80 beats per minute) | During the first 24 hours of life. | 
| Clinical: Bronchopulmonary dysplasia (BPD) | BPD, maximum grade [number of cases] | At 36 weeks postmenstrual age. | 
| Clinical: Intraventricular haemorrhage (IVH) | IVH, maximum grade [number of cases] | At 36 weeks postmenstrual age. | 
| Clinical: Retinopathy of prematurity (ROP) | ROP, maximum grade [number of cases] | At 36 weeks postmenstrual age. | 
| Clinical: Necrotizing enterocolitis (NEC) | NEC, surgically treated [number of cases] | At 36 weeks postmenstrual age. | 
| Clinical: Blood-culture positive sepsis | Blood-culture positive sepsis [number of cases] | At 36 weeks postmenstrual age. |