Surfactant Nebulization for the Early Aeration of the Preterm Lung (SUNSET)

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

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.

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Respiratory Distress Syndrome; Surfactant Deficiency Syndrome Neonatal
• Intervention / Treatment: Drug: Surfactant nebulisation

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Department of Neonatology, University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surfactant nebulisation; 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; 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).
No Intervention: Standard care; The control group will receive standard care (PEEP, +/- noninvasive positive pressure ventilation, without surfactant nebulisation).

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Death	Death [number of cases]	Until 36 weeks postmenstrual age.
Safety: Pulmonary haemorrhage	Pulmonary haemorrhage [number of cases]	Until 36 weeks postmenstrual age.
Safety: Air leak	Air leak [number of cases]	Until 36 weeks postmenstrual age.

Collaborators and Investigators

• Sponsor: University of Zurich

Publications and helpful links

General Publications

• Gaertner VD, Waldmann AD, Bassler D, Hooper SB, Ruegger CM. Intrapulmonary Volume Changes during Hiccups versus Spontaneous Breaths in a Preterm Infant. Neonatology. 2022;119(4):525-529. doi: 10.1159/000524194. Epub 2022 Apr 8.
• Minocchieri S, Berry CA, Pillow JJ; CureNeb Study Team. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019 May;104(3):F313-F319. doi: 10.1136/archdischild-2018-315051. Epub 2018 Jul 26. Erratum In: Arch Dis Child Fetal Neonatal Ed. 2020 Mar;105(2):e1. doi: 10.1136/archdischild-2018-315051corr1.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): January 16, 2022

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 19, 2020

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Syndrome; Premature Birth; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: SUNSET

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