Lung UltrasouNd Guided Surfactant Therapy in Preterm Infants (LUNG Study)

NCT05198375 | Terminated DMC

• 1 other identifier: 302/2021
• Study Type: interventional
• Target: 411
• Locations: 2 countries
• Sites: 18

Brief Summary

The investigators hypothesized that the use of lung ultrasound (LU) for measuring RDS severity and deciding surfactant treatment thresholds might decrease the incidence of early and late sequelae in the study group. Thus, a timely surfactant therapy would eventually improve short (e.g. Need of mechanical ventilation in the first 3 days) and more long-term outcomes, such as BPD or death. To confirm this hypothesis, the investigators planned an international multicenter randomized controlled study in which preterm infants will be randomized into two groups: one will be managed deciding surfactant treatment of preterm infants with RDS on the basis of a cut-off value of FiO2 as for European guidelines, and one will be managed deciding surfactant treatment using a LU score cut-off and/or FiO2. Primary endpoint will be the reduction in proportion of infants with BPD or death in the group managed with LU compared to the control group

Conditions

Respiratory Distress Syndrome, Newborn

Outcome Measures

Primary Outcomes (1)

• BPD or Death reduction

  Primary endpoint will be the difference in proportion of infants with BPD (defined as Bancalari, Jobe 2001) or death in the group managed with LUS compared to the control group.

  36 weeks of gestational age or at the moment of discharge

Secondary Outcomes (18)

• Proportion of infants treated "early" (before 3 hours of life) vs late

  First 3 hours of life

• Age in minute at the first surfactant administration

  First 12 hours of life

• Needs of mechanical ventilation in the first 3 days of life

  First 3 days of life

• Max FiO2 value before surfactant treatment

  First 12 hours of life

• FiO2/SpO2 ratio before surfactant treatment

  First 12 hours of life

Study Arms (2)

Control group (CG)

ACTIVE COMPARATOR

decision to administer exogenous surfactant when FiO2 \>0.30 on nCPAP (pressure 6-8 cmH20) to maintain preductal SpO2 between 90 and 95%.

Diagnostic Test: Lung ultrasound score (LUS)

LUS group (LUSG)

EXPERIMENTAL

decision to administer surfactant when LUS \> 8 on nCPAP (pressure 6-8 cmH20) to maintain preductal SpO2 between 90 and 95%. The LUS group will receive surfactant administration as rescue therapy in case of LUS \< or = 8 but FiO2 \> 0.30 on nCPAP (pressure 6-8 cmH20) to maintain preductal SpO2 between 90 and 95%.

Diagnostic Test: Lung ultrasound score (LUS)

Interventions

Lung ultrasound score (LUS) DIAGNOSTIC_TEST

LU score (LUS) will be performed between 1 and 3 hours of life. LUS will be calculated by performing longitudinal scans of the chest in the anterior (midclavicular line), lateral (anterior axillary line) and posterior (posterior axillary line) area bilaterally using high-frequency linear or micro linear (hockey stick) probe. A score from 0 to 3 will be assigned to each area based on the ultrasound detected pattern.

Control group (CG); LUS group (LUSG)

Eligibility Criteria

• Age: 1 Minute - 3 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• In-born infants at 25+0-29+6 weeks of gestational age
• Spontaneously breathing at birth but requiring noninvasive respiratory support with nCPAP at a pressure of 6-8 cmH2O to maintain an SpO2 between 90% and 95%.
• Parental consent has been obtained

You may not qualify if:

• Endotracheal intubation in the delivery room for resuscitation or insufficient respiratory drive according to European guidelines
• Prolonged premature rupture of membranes (PROM) for more than 3 days
• Presence of major congenital malformations or chromosomal anomalies
• Hydrops fetalis
• Inherited disorders of metabolism
• Administration of surfactant before performing the LUS.
• Other respiratory diseases than RDS

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead

Study Sites (18)

Neonatal intensive care unit - Azienda Sanitaria dell'Alto Adige

Bolzano, Italy

Location

Spedali Civili di Brescia

Brescia, Italy

Location

AOU Careggi

Florence, 50134, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano

Milan, Italy

Location

Neonatal Intensive Care Unit Ospedale dei Bambini "Vittore Buzzi"

Milan, Italy

Location

Neonatal Intensive Care Unit Modena

Modena, Italy

Location

Neonatal Intensive Care Unit - Federico II University

Napoli, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy

Location

Neonatologia e Terapia Intensiva Neonatale Rimini

Rimini, Italy

Location

Fondazione Policlinico Gemelli

Roma, Italy

Location

Azienda sanitaria universitaria Friuli Centrale

Udine, Italy

Location

NICU AOUI Verona

Verona, Italy

Location

Germans Trias i Pujol

Badalona, Spain, 08916, Spain

Location

Neonatal Intensive Care Unit Coruña

A Coruña, Spain

Location

Barcelona Center for Maternal Fetal and Neonatal Medicine

Barcelona, Spain

Location

Neonatal Intensive Care Unit, Puerta del Mar Universitary Hospital, Cádiz.

Cadiz, Spain

Location

Hospital Gregorio Maranon

Madrid, Spain

Location

Hospital Alvaro Cunqueiro de Vigo. Instituto de Investigación Galicia Sur

Vigo, Spain

Location

Related Publications (16)

• Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update. Neonatology. 2019;115(4):432-450. doi: 10.1159/000499361. Epub 2019 Apr 11.

  PMID: 30974433 BACKGROUND

• Bahadue FL, Soll R. Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD001456. doi: 10.1002/14651858.CD001456.pub2.

  PMID: 23152207 BACKGROUND

• Raschetti R, Yousef N, Vigo G, Marseglia G, Centorrino R, Ben-Ammar R, Shankar-Aguilera S, De Luca D. Echography-Guided Surfactant Therapy to Improve Timeliness of Surfactant Replacement: A Quality Improvement Project. J Pediatr. 2019 Sep;212:137-143.e1. doi: 10.1016/j.jpeds.2019.04.020. Epub 2019 May 10.

  PMID: 31079857 BACKGROUND

• Rodriguez-Fanjul J, Jordan I, Balaguer M, Batista-Munoz A, Ramon M, Bobillo-Perez S. Early surfactant replacement guided by lung ultrasound in preterm newborns with RDS: the ULTRASURF randomised controlled trial. Eur J Pediatr. 2020 Dec;179(12):1913-1920. doi: 10.1007/s00431-020-03744-y. Epub 2020 Jul 24.

  PMID: 32710304 BACKGROUND

• Brat R, Yousef N, Klifa R, Reynaud S, Shankar Aguilera S, De Luca D. Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. JAMA Pediatr. 2015 Aug;169(8):e151797. doi: 10.1001/jamapediatrics.2015.1797. Epub 2015 Aug 3.

  PMID: 26237465 BACKGROUND

• De Martino L, Yousef N, Ben-Ammar R, Raimondi F, Shankar-Aguilera S, De Luca D. Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates. Pediatrics. 2018 Sep;142(3):e20180463. doi: 10.1542/peds.2018-0463. Epub 2018 Aug 14.

  PMID: 30108142 BACKGROUND

• De Luca D, van Kaam AH, Tingay DG, Courtney SE, Danhaive O, Carnielli VP, Zimmermann LJ, Kneyber MCJ, Tissieres P, Brierley J, Conti G, Pillow JJ, Rimensberger PC. The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity. Lancet Respir Med. 2017 Aug;5(8):657-666. doi: 10.1016/S2213-2600(17)30214-X. Epub 2017 Jul 4.

  PMID: 28687343 BACKGROUND

• Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.

  PMID: 11401896 BACKGROUND

• Corsini I, Parri N, Ficial B, Dani C. Lung ultrasound in the neonatal intensive care unit: Review of the literature and future perspectives. Pediatr Pulmonol. 2020 Jul;55(7):1550-1562. doi: 10.1002/ppul.24792. Epub 2020 Apr 27.

  PMID: 32339409 BACKGROUND

• Madar J, Roehr CC, Ainsworth S, Ersdal H, Morley C, Rudiger M, Skare C, Szczapa T, Te Pas A, Trevisanuto D, Urlesberger B, Wilkinson D, Wyllie JP. European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth. Resuscitation. 2021 Apr;161:291-326. doi: 10.1016/j.resuscitation.2021.02.014. Epub 2021 Mar 24.

  PMID: 33773829 BACKGROUND

• Raimondi F, Migliaro F, Corsini I, Meneghin F, Pierri L, Salome S, Perri A, Aversa S, Nobile S, Lama S, Varano S, Savoia M, Gatto S, Leonardi V, Capasso L, Carnielli VP, Mosca F, Dani C, Vento G, Dolce P, Lista G. Neonatal Lung Ultrasound and Surfactant Administration: A Pragmatic, Multicenter Study. Chest. 2021 Dec;160(6):2178-2186. doi: 10.1016/j.chest.2021.06.076. Epub 2021 Jul 19.

  PMID: 34293317 BACKGROUND

• Raimondi F, Migliaro F, Corsini I, Meneghin F, Dolce P, Pierri L, Perri A, Aversa S, Nobile S, Lama S, Varano S, Savoia M, Gatto S, Leonardi V, Capasso L, Carnielli VP, Mosca F, Dani C, Vento G, Lista G. Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome. Pediatrics. 2021 Apr;147(4):e2020030528. doi: 10.1542/peds.2020-030528. Epub 2021 Mar 9.

  PMID: 33688032 BACKGROUND

• de Vries LS, Eken P, Dubowitz LM. The spectrum of leukomalacia using cranial ultrasound. Behav Brain Res. 1992 Jul 31;49(1):1-6. doi: 10.1016/s0166-4328(05)80189-5.

  PMID: 1388792 BACKGROUND

• International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005 Jul;123(7):991-9. doi: 10.1001/archopht.123.7.991.

  PMID: 16009843 BACKGROUND

• Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978 Jan;187(1):1-7. doi: 10.1097/00000658-197801000-00001.

  PMID: 413500 BACKGROUND

• Corsini I, Rodriguez-Fanjul J, Raimondi F, Boni L, Berardi A, Aldecoa-Bilbao V, Alonso-Ojembarrena A, Ancora G, Aversa S, Beghini R, Meseguer NB, Capasso L, Chesi F, Ciarcia M, Concheiro A, Corvaglia L, Ficial B, Filippi L, Carballal JF, Fusco M, Gatto S, Ginovart G, Gregorio-Hernandez R, Lista G, Sanchez-Luna M, Martini S, Massenzi L, Miselli F, Mercadante D, Mosca F, Palacio MT, Perri A, Piano F, Prieto MP, Fernandez LR, Risso FM, Savoia M, Staffler A, Vento G, Dani C. Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study). Trials. 2023 Nov 4;24(1):706. doi: 10.1186/s13063-023-07745-8.

  PMID: 37925512 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn

Condition Hierarchy (Ancestors)

Respiratory Distress Syndrome; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Iuri Corsini, MD

  Careggi University Hospital of Florence

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatologist at the Careggi University Hospital NICU

Study Record Dates

• First Submitted: December 25, 2021
• First Posted: January 20, 2022
• Study Start: April 5, 2022
• Primary Completion: May 23, 2025
• Study Completion: May 23, 2025
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (12); ES (6)