Enteral Nutrition Tolerance And REspiratory Support (ENTARES)

NCT03548324 | Completed

• 1 other identifier: ENTARES
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 13

Brief Summary

This research study aims to evaluate the relation between non-invasive ventilation and feeding tolerance in preterms with respiratory distress syndrome (RDS). To this purpose a multicenter randomized controlled trial was designed. It will involve 13 neonatal intensive care units (NICUs) in Italy and will be coordinated by the NICU of the University of Turin. The study focuses on the impact of two non-invasive respiratory support techniques (NCPAP and HHHFNC) on feeding intolerance and gastrointestinal complications to identify which technique is the most effective and safe in preterms with RDS. Further aim is to identify which technique could be the most suitable for full enteral feeding achievement and acquisition of oral feeding. Improving enteral feeding tolerance and promoting oral feeding could improve clinical outcomes and reduce risks and costs of prolonged hospital stay. Further aim is to evaluate the response to NCPAP and HHHFNC in the treatment of RDS, focusing on a population of extremely low preterms.

Conditions

Very Low Birth Weight Infant; Respiratory Distress Syndrome in Premature Infant; Enteral Feeding Intolerance

Keywords

Feeding Tolerance; RDS; HFNC; NCPAP; Preterm; NEC; Enteral Nutrition; Non Invasive Respiratory Support; Very Low Birth Weight Infant

Outcome Measures

Primary Outcomes (1)

• Full Enteral Feeding (FEF) time

  Time to reach Full Enteral Feeding, defined as an enteral intake of 150 mL/kg/die (n. of days)

  From date of randomization until the date of hospital discharge or date of death, whichever came first, assessed up to 6 months

Secondary Outcomes (14)

• Half Enteral Feeding (HEF) time

  From date of randomization until the date of hospital discharge or date of death, whichever came first, assessed up to 6 months

• Enteral feeding interruptions

  From date of randomization until the date of hospital discharge or date of death, whichever came first, assessed up to 6 months

• Not given feeds

  From date of randomization until the date of hospital discharge or date of death, whichever came first, assessed up to 6 months

• Pathologic gastric residuals

  From date of randomization until the date of hospital discharge or date of death, whichever came first, assessed up to 6 months

• Vomits and/or regurgitations

  From date of randomization until the date of hospital discharge or date of death, whichever came first, assessed up to 6 months

Study Arms (2)

HHHFNC

ACTIVE COMPARATOR

Heated Humidified High Flow Nasal Cannulae

Device: HHHFNC

NCPAP

ACTIVE COMPARATOR

Nasal Continuous Positive Air Pressure

Device: NCPAP

Interventions

HHHFNC DEVICE

Application to HHHFNC to treat respiratory distress syndrome in preterm infants previously demonstrated to be stable on a non-invasive respiratory support (HHHFNC or NCPAP).

HHHFNC

NCPAP DEVICE

Application to NCPAP to treat respiratory distress syndrome in preterm infants previously demonstrated to be stable on a non-invasive respiratory support (HHHFNC or NCPAP).

NCPAP

Eligibility Criteria

• Age: 25 Weeks - 29 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• diagnosis of RDS
• stability on HHHFNC or NCPAP since at least 48 hours (SatO2 TC 90-95%, pCO2 ≤ 60 mmHg, FiO2 \< 40%, Silverman score ≤ 6, ≤ 2 apnea episodes/hour with CPAP ≤ 7 cmH2O if on NCPAP and flow ≤ 6 L/min if on HHHFNC )
• ≤ 7 days of life
• suitability to start enteral feeding (if not already started)
• parental written consent

You may not qualify if:

• neurological or surgical diseases
• sepsis
• chromosomal abnormalities or major malformations

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (13)

AOUC Policlinico di Bari

Bari, Bari (BA), Italy

Location

ASL Ospedale Di Venere

Bari, Bari (BA), Italy

Location

Ospedale Sana Croce e Carle

Cuneo, CN, Italy

Location

AOU Careggi

Florence, Firenze (FI), Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Milano (MI), Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Mangiagalli)

Milan, Milano (MI), Italy

Location

Ospedale dei Bambini Vittore Buzzi

Milan, MI, Italy

Location

AOU Federico II

Napoli, Napoli (NA), Italy

Location

Ospedale San Matteo

Pavia, PV, Italy

Location

Fondazione Policlinico Universitario A. Gemelli

Roma, Roma (RM), Italy

Location

AOU Città della Salute e della Scienza di Torino - Ospedale S.Anna

Torino, Torino (TO), Italy

Location

AOU Città della Salute e della Scienza di Torino - Ospedale S.Anna

Torino, TO, 10126, Italy

Location

ASST Sette Laghi Polo Universitario

Varese, Varese (VA), Italy

Location

Related Publications (16)

• Davies PL, Maxwell NC, Kotecha S. The role of inflammation and infection in the development of chronic lung disease of prematurity. Adv Exp Med Biol. 2006;582:101-10. doi: 10.1007/0-387-33026-7_9.

  PMID: 16802622 BACKGROUND

• Lista G, Maturana A, Moya FR. Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU. Eur J Pediatr. 2017 Oct;176(10):1287-1293. doi: 10.1007/s00431-017-2984-y. Epub 2017 Aug 10.

  PMID: 28795220 BACKGROUND

• Aly H. Ventilation without tracheal intubation. Pediatrics. 2009 Aug;124(2):786-9. doi: 10.1542/peds.2009-0256. Epub 2009 Jul 27. No abstract available.

  PMID: 19651592 BACKGROUND

• Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks' gestation: a randomized, controlled trial. J Perinatol. 2012 May;32(5):336-43. doi: 10.1038/jp.2012.1. Epub 2012 Feb 2.

  PMID: 22301528 BACKGROUND

• Fischer HS, Buhrer C. Avoiding endotracheal ventilation to prevent bronchopulmonary dysplasia: a meta-analysis. Pediatrics. 2013 Nov;132(5):e1351-60. doi: 10.1542/peds.2013-1880. Epub 2013 Oct 21.

  PMID: 24144716 BACKGROUND

• Schmolzer GM, Kumar M, Pichler G, Aziz K, O'Reilly M, Cheung PY. Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis. BMJ. 2013 Oct 17;347:f5980. doi: 10.1136/bmj.f5980.

  PMID: 24136633 BACKGROUND

• Wilkinson D, Andersen C, O'Donnell CP, De Paoli AG, Manley BJ. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2016 Feb 22;2(2):CD006405. doi: 10.1002/14651858.CD006405.pub3.

  PMID: 26899543 BACKGROUND

• Kotecha SJ, Adappa R, Gupta N, Watkins WJ, Kotecha S, Chakraborty M. Safety and Efficacy of High-Flow Nasal Cannula Therapy in Preterm Infants: A Meta-analysis. Pediatrics. 2015 Sep;136(3):542-53. doi: 10.1542/peds.2015-0738. Epub 2015 Aug 17.

  PMID: 26283781 BACKGROUND

• Yoder BA, Manley B, Collins C, Ives K, Kugelman A, Lavizzari A, McQueen M. Consensus approach to nasal high-flow therapy in neonates. J Perinatol. 2017 Jul;37(7):809-813. doi: 10.1038/jp.2017.24. Epub 2017 Mar 23.

  PMID: 28333157 BACKGROUND

• Salvo V, Lista G, Lupo E, Ricotti A, Zimmermann LJI, Gavilanes AWD, Gitto E, Colivicchi M, Ferrau V, Gazzolo D. Comparison of three non-invasive ventilation strategies (NSIPPV/BiPAP/NCPAP) for RDS in VLBW infants. J Matern Fetal Neonatal Med. 2018 Nov;31(21):2832-2838. doi: 10.1080/14767058.2017.1357693. Epub 2017 Aug 1.

  PMID: 28718356 BACKGROUND

• Mihatsch WA, Pohlandt F, Franz AR, Flock F. Early feeding advancement in very low-birth-weight infants with intrauterine growth retardation and increased umbilical artery resistance. J Pediatr Gastroenterol Nutr. 2002 Aug;35(2):144-8. doi: 10.1097/00005176-200208000-00008.

  PMID: 12187288 BACKGROUND

• Parker L, Torrazza RM, Li Y, Talaga E, Shuster J, Neu J. Aspiration and evaluation of gastric residuals in the neonatal intensive care unit: state of the science. J Perinat Neonatal Nurs. 2015 Jan-Mar;29(1):51-9; quiz E2. doi: 10.1097/JPN.0000000000000080.

  PMID: 25633400 BACKGROUND

• Li YF, Lin HC, Torrazza RM, Parker L, Talaga E, Neu J. Gastric residual evaluation in preterm neonates: a useful monitoring technique or a hindrance? Pediatr Neonatol. 2014 Oct;55(5):335-40. doi: 10.1016/j.pedneo.2014.02.008. Epub 2014 Aug 14.

  PMID: 25129325 BACKGROUND

• Gephart SM, Fleiner M, Kijewski A. The ConNECtion Between Abdominal Signs and Necrotizing Enterocolitis in Infants 501 to 1500 g. Adv Neonatal Care. 2017 Feb;17(1):53-64. doi: 10.1097/ANC.0000000000000345.

  PMID: 27754992 BACKGROUND

• Cresi F, Maggiora E, Lista G, Dani C, Borgione SM, Spada E, Ferroglio M, Bertino E, Coscia A; ENTARES Study Group. Effect of Nasal Continuous Positive Airway Pressure vs Heated Humidified High-Flow Nasal Cannula on Feeding Intolerance in Preterm Infants With Respiratory Distress Syndrome: The ENTARES Randomized Clinical Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2323052. doi: 10.1001/jamanetworkopen.2023.23052.

  PMID: 37436750 DERIVED

• Cresi F, Maggiora E, Borgione SM, Spada E, Coscia A, Bertino E, Meneghin F, Corvaglia LT, Ventura ML, Lista G; ENTARES Study Research Group. Enteral Nutrition Tolerance And REspiratory Support (ENTARES) Study in preterm infants: study protocol for a randomized controlled trial. Trials. 2019 Jan 18;20(1):67. doi: 10.1186/s13063-018-3119-0.

  PMID: 30658676 DERIVED

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Francesco Cresi, MD, PhD

  Città della Salute e della Scienza, S.C. Neonatologia U., University of Turin

  STUDY DIRECTOR

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: Principal Investigator

Model Details: Two arms multicenter randomized controlled trial designed according to the intention-to-treat model. The assignement to one of the two arms (NCPAP or HHHFNC) is by block randomization. The randomization program is designed to obtain, in each research unit, a balance between the two arms according to gestation age (GA \<28 weeks and GA ≥ 28 weeks).

Study Record Dates

• First Submitted: April 28, 2018
• First Posted: June 7, 2018
• Study Start: January 2, 2019
• Primary Completion: September 30, 2021
• Study Completion: October 30, 2021
• Last Updated: August 23, 2022

Record last verified: 2022-08

Locations

IT (13)