Comparison of “IN-REC-SUR-E” and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN- REC-LISA trial)
Authors: Vento Giovanni , Paladini Angela , Aurilia Claudia , Ozdemir Senem Alkan , Carnielli Virgilio Paolo , Cools Filip , Costa Simonetta , Cota Francesco , Dani Carlo , Davis Peter G. , Fattore Simona , Fè Claudia , Finer Neil , Fusco Francesca Paola , Gizzi Camilla , Herting Egbert , Jian Mao , Lio Alessandra , Lista Gianluca , Mosca Fabio , Nobile Stefano , Perri Alessandro , Picone Simona , Pillow Jane , Polglase Graeme , Pasciutto Tina , Pastorino Roberta , Tana Milena , Tingay David , Tirone Chiara , vankaam Anton , Ventura Maria Luisa , Aceti Arianna , Agosti Massimo , Alighieri Gianni , Ancora Gina , Angileri Vita , Ausanio Gaetano , Aversa Salvatore , Balestri Eleonora , Baraldi Eugenio , Barbini Maria Cristina , Barone Ciro , Beghini Renzo , Bellan Cristina , Berardi Alberto , Bernardo Italo , Betta Pasqua , Binotti Marco , Bizzarri Bianca , Borgarello Gabriella , Borgione Silvia , Borrelli Angela , Bottino Roberto , Bracaglia Giorgio , Bresesti Ilia , Burattini Ilaria , Cacace Caterina , Calzolari Francesca , Campagnoli Maria Francesca , Capasso Letizia , Capozza Manuela , Capretti Mariagrazia , Caravetta Jacopo , Carbonara Caterina , Cardilli Viviana , Carta Maurizio , Castoldi Francesca , Castronovo Antonella , Cavalleri Elisa , Cavigioli Francesco , Cecchi Sara , Chierici Valentina , Cimino Carla , Cocca Francesco , Cocca Carmen , Cogo Paola , Coma Martina , Comito Valentina , Condò Valentin , Consiglia Chiara , Conti Rossella , Corradi Mara , Corsello Giovanni , Corvaglia Luigi T. , Costa Antonino , Coscia Alessandra , Cresi Francesco , Crespino Francesco , D'Amico Pietro , De Cosmo Lucrezia , De Maio Cinzia , Campo Giuliana Del , Credico Simona Di , Fabio Sandra Di , Nicola Paola Di , Paolo Ambriogio Di , Distilo Antonietta , Valerio Susanna Di , Duca Vincenzo , Falcone Alessandra , Falsaperla Raffaele , Fasolato Valeria , Fatuzzo Valentina , Favini Francesca , Ferrarello Maria Pia , Ferrari Stefania , Nastro Francesca Fiori , Forcellini Carlo Alberto , Frachiolla Annalisa , Gabriele Angela , Galdo Francesca , Gallini Francesca , Gangemi Antonella , Gargano Giancarlo , Gazzolo Diego , Gentile Maria Paola , Ghirardello Stefano , Giardina Fabio , Giordano Lucio , Giuffrè Mario , Yildirim Tuling Gokmen , Grappone Lidia , Grasso Fiorentino , Greco Irene , Grison Alessandra , Guglielmino Rosanna , Guidotti Isotta , Guzzo Immacolata , Forgia Nicola La , Placa Simona La , Torre Giuseppe La , Lago Paola , Lanciotti Lucia , Lavizzari Anna , Leo Francesco , Leonardi Valentina , Li Juan , Liberatore Pio , Lodin Danila , Lubrano Riccardo , Lucente Mariella , Luciani Stefano , Luvarà Dimenica , Maffei Gianfranco , Maggio Alessandra , Maggio Luca , Maiolo Kim , Malaigia Laura , Mangili Giovanna , Manna Angelo , Maranella Eugenia , Marciano Alessandra , Marcozzi Paola , Marletta Marisa , Marseglia Lucia , Martinelli Domenico , Massari Simona , Massenzi Luca , Matina Federico , Mattia Loretta , Mescoli Giovanna , Migliore Ignazia Valentina , Minghetti Diego , Mondello Isabella , Montano Simona , Morandi Grazia , Mores Nadia , Morreale Sabrina , Morselli Ezio , Motta Mario , Napolitano Marcello , Nardo Daniel , Nicolardi Aessandra , Nider Silvia , Nigro Gabriella , Nuccio Melissa , Orfeo Luigi , Ottaviano Carla , Paganin Paola , Palamides Sabrina , Palatta Sara , Paolillo Piermichele , Pappalardo Maria Grazia , Pasta Elisa , Patti Letizia , Paviotti Giulia , Perniola Roberto , Perotti Gianfranco , Perrone Serafina , Petrillo Flavia , Piazza Maria Santa , Piccirillo Alessandro , Pierro Maria , Piga Enrico , Pingitore Giulia Anna , Pisu Simona , Pittini Carla , Pontiggia Federica , Pontrelli Giovanna , Primavera Adele , Proto Alice , Quartulli Lorenzo , Raimondi Francesco , Ramenghi Luca , Rapsomaniki Maria , Ricotti Alberto , Rigotti Camilla , Rinaldi Matteo , Risso Francesco , Roma Enza , Romanini Enzo , Romano Valerio , Rosati Enrico , Rosella Vincenzo , Rulli Imma , Salvo Vincenzo , Sanfilippo Cinzia , Sannia Andrea , Saporito Alessandro , Sauna Alessandra , Scapillati Eleonora , Schettini Federico , Scorrano Antonio , Mantelli Simona Semeria , Sepporta Vittoria , Sindico Paola , Solinas Agostina , Sorrentino Elena , Spaggiari Eugenio , Staffler Alex , Stella Marcello , Termini Donatella , Terrin Gianluca , Testi Alessia , Tina Gabriella , Tirantello Massimo , Tomassini Barbara , Tormena Francesca , Travan Laura , Trevisanuto Daniele , Tulino Viviana , Valenzano Luigia , Vedovato Stefania , Vendramin Silvia , Villani Paolo , Viola Serena , Viola Valeria , Vitaliti Giuliana , Vitaliti Marcello , Wanker Petra , Yang Yuchen , Zanetta Sara , Zannin Emanuela 
Published: April 2024

Abstract

Background:
Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). Goals of different methods of surfactant administration are to reduce duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD), however the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration.
Methods:
In this study 382 infants born at 24+0-27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. Secondary outcomes are: BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular haemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include centre and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks).
Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR).
Discussion:
This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 hours of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life.
Trial registration: ClinicalTrials.gov identifier NCT05711966