Enteral Nutrition Tolerance And REspiratory Support (ENTARES) Study in preterm infants: study protocol for a randomized controlled trial

Francesco Cresi, Elena Maggiora, Silvia Maria Borgione, Elena Spada, Alessandra Coscia, Enrico Bertino, Fabio Meneghin, Luigi Tommaso Corvaglia, Maria Luisa Ventura, Gianluca Lista, ENTARES Study Research Group, Fabio Mosca, Anna Orsi, Domenica Mercadante, Stefano Martinelli, Laura Ilardi, Alice Proto, Sara Gatto, Arianna Aceti, Fabrizio Sandri, Roksana Chakrokh, Nicola Laforgia, Antonio Di Mauro, Maria E Baldassarre, Antonio Del Vecchio, Flavia Petrillo, Maria P Spalierno, Francesco Raimondi, Letizia Capasso, Marta Palma, Daniele Farina, Maria F Campagnoli, Tatiana Boetti, Federica Logrippo, Massimo Agosti, Laura Morlacchi, Simona Perniciaro, Carlo Dani, Serena Elia, Giovanni Vento, Luca Maggio, Mauro Stronati, Elisa Civardi, Grappone Lidia, Borrelli Angela, Francesco Cresi, Elena Maggiora, Silvia Maria Borgione, Elena Spada, Alessandra Coscia, Enrico Bertino, Fabio Meneghin, Luigi Tommaso Corvaglia, Maria Luisa Ventura, Gianluca Lista, ENTARES Study Research Group, Fabio Mosca, Anna Orsi, Domenica Mercadante, Stefano Martinelli, Laura Ilardi, Alice Proto, Sara Gatto, Arianna Aceti, Fabrizio Sandri, Roksana Chakrokh, Nicola Laforgia, Antonio Di Mauro, Maria E Baldassarre, Antonio Del Vecchio, Flavia Petrillo, Maria P Spalierno, Francesco Raimondi, Letizia Capasso, Marta Palma, Daniele Farina, Maria F Campagnoli, Tatiana Boetti, Federica Logrippo, Massimo Agosti, Laura Morlacchi, Simona Perniciaro, Carlo Dani, Serena Elia, Giovanni Vento, Luca Maggio, Mauro Stronati, Elisa Civardi, Grappone Lidia, Borrelli Angela

Abstract

Background: Respiratory distress syndrome (RDS) and feeding intolerance are common conditions in preterm infants and among the major causes of neonatal mortality and morbidity. For many years, preterm infants with RDS have been treated with mechanical ventilation, increasing risks of acute lung injury and bronchopulmonary dysplasia. In recent years non-invasive ventilation techniques have been developed. Showing similar efficacy and risk of bronchopulmonary dysplasia, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) have become the most widespread techniques in neonatal intensive care units. However, their impact on nutrition, particularly on feeding tolerance and risk of complications, is still unknown in preterm infants. The aim of the study is to evaluate the impact of NCPAP vs HHHFNC on enteral feeding and to identify the most suitable technique for preterm infants with RDS.

Methods: A multicenter randomized single-blind controlled trial was designed. All preterm infants with a gestational age of 25-29 weeks treated with NCPAP or HHHFNC for RDS and demonstrating stability for at least 48 h along with the compliance with inclusion criteria (age less than 7 days, need for non-invasive respiratory support, suitability to start enteral feeding) will be enrolled in the study and randomized to the NCPAP or HHHFNC arm. All patients will be monitored until discharge, and data will be analyzed according to an intention-to-treat model. The primary outcome is the time to reach full enteral feeding, while parameters of respiratory support, feeding tolerance, and overall health status will be evaluated as secondary outcomes. The sample size was calculated at 141 patients per arm.

Discussion: The identification of the most suitable technique (NCPAP vs HHHFNC) for preterm infants with feeding intolerance could reduce gastrointestinal complications, improve growth, and reduce hospital length of stay, thus improving clinical outcomes and reducing health costs. The evaluation of the timing of oral feeding could be useful in understanding the influence that these techniques could have on the development of sucking-swallow coordination. Moreover, the evaluation of the response to NCPAP and HHHFNC could clarify their efficacy as a treatment for RDS in extremely preterm infants.

Trial registration: ClinicalTrials.gov, NCT03548324 . Registered on 7 June 2018.

Keywords: Enteral nutrition; Feeding intolerance; HFNC; NCPAP; NEC; Non-invasive ventilation; Preterm; RDS; Very low birth weight infant.

Conflict of interest statement

Ethics approval and consent to participate

Study protocol was approved with the approval number 0043331 on 24th March 2018 by the ethics committee of the coordinating unit (Comitato Etico Interaziendale – AOU Città della Salute e della Scienza di Torino; phone: + 39.011.6336547; email: comitatoetico@cittadellasalute.to.it).

The study protocol will be subsequently submitted to the ethics committees of each participating unit.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Design of the study
Fig. 2
Fig. 2
SPIRIT figure

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