Efficacy of a New Technique -"IN-REC-SUR-E"- in Preterm Neonates With RDS

NCT02482766 | Completed DMC

• 1 other identifier: Prot. rs 25882/14
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 33

Brief Summary

The primary hypothesis of this study is reduction in need of mechanical ventilation in the first 72 hours of life (excluding the transient tracheal intubation performed for surfactant administration and the mechanical ventilation for lung recruitment) in spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 hours of life who received an HFOV recruitment maneuver (IN-REC-SUR-E) compared to no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation.

Conditions

Respiratory Distress Syndrome; Hyaline Membrane Disease

Outcome Measures

Primary Outcomes (1)

• Need for mechanical ventilation within the first 3 days of life and therefore we consider IN-REC-SUR-E a success if mechanical ventilation is not required and a failure if the infant needs mechanical ventilation in the first 72 hours.

  First 72 hours of life

Secondary Outcomes (8)

• Duration of NCPAP

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

• Duration of conventional mechanical ventilation

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

• Duration of High-frequency oscillatory ventilation (HFOV)

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

• Duration of O2-therapy

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

• Duration of hospitalization

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

Other Outcomes (12)

• Air leaks

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

• Pulmonary hemorrage

  First 72 hours of life

• PDA and need of surgical closure

  Participants will be followed for the duration of hospital stay, an expected average of 12 weeks

Study Arms (2)

INRECSURE

EXPERIMENTAL

Infants in the INRECSURE arm will undergo the following approach: as soon as possible after the recruitment manoeuver (at CDP-Optimal) a dose of poractant alfa (Curosurf \[Chiesi Farmaceutici, Parma, Italy\]) of 200 mg/kg will be administered via a closed administration system in one-two aliquots (1-2 minutes). The tube position will be confirmed by auscultation. A temporary reduction of frequency may be necessary to increase the VT up to 2.5 ml/kg for improving the surfactant spreading.

Drug: Poractant alfa, 200 mg/kg; Device: Ventilator for High-frequency Oscillatory Ventilation (HFOV); Device: Nasal Continuous Positive Airway Pressure (nCPAP)

INSURE

ACTIVE COMPARATOR

Infants in the INSURE arm will undergo the following approach: after intubation, a dose of poractant alfa (Curosurf \[Chiesi Farmaceutici, Parma, Italy\]) of 200 mg/kg will be administered via a closed administration system in one-two aliquots (1-2 minutes). The tube position will be confirmed by auscultation. During surfactant administration, infants will be manually ventilated to facilitate surfactant distribution.

Drug: Poractant alfa, 200 mg/kg; Device: Nasal Continuous Positive Airway Pressure (nCPAP)

Interventions

Poractant alfa, 200 mg/kg DRUG

Endotracheal Surfactant administration

Also known as: Curosurf-Chiesi Farmaceutici, Parma, Italy

INRECSURE; INSURE

Ventilator for High-frequency Oscillatory Ventilation (HFOV) DEVICE

This device will be used to perform an HFOV recruitment maneuver before surfactant administration

INRECSURE

Nasal Continuous Positive Airway Pressure (nCPAP) DEVICE

After surfactant administration, the babies will be extubated within 30 minutes and will receive nCPAP (6-8 cm H2O)

INRECSURE; INSURE

Eligibility Criteria

• Age: 24 Weeks - 27 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• In-Born at 24+0-27+6 (and)
• Spontaneously breathing at birth but requiring respiratory support (CPAP or O2) at 5' of life (and)
• Parental consent has been obtained (and)
• Failing nCPAP during the first 24 hours of life

You may not qualify if:

• Severe birth asphyxia or a 5-minute Apgar score \<3
• Endotracheal intubation in the delivery room for resuscitation or insufficient respiratory drive according to AAP guidelines16
• Prolonged PROM \> 3 weeks
• Presence of major congenital malformations
• Hydrops fetalis
• Inherited disorders of metabolism

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead
• Ospedali Riuniti Ancona: collaborator
• Careggi Hospital: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• Centre for Neonatal Research and Education, Crawley, West Australia: collaborator
• Monash University: collaborator
• Azienda Ospedaliera San Gerardo di Monza: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (33)

Ospedale Salesi

Ancona, AN, Italy

Location

Ospedale Di Venere

Bari, BA, Italy

Location

Ospedale Maggiore

Bologna, BO, Italy

Location

Fondazione Poliambulanza

Brescia, BS, Italy

Location

Ospedale di Bolzano

Bolzano, BZ, Italy

Location

Pineta Grande

Caserta, CE, 81030, Italy

Location

S. Sebastiano e S. Anna

Caserta, CE, Italy

Location

Azienda Ospedaliera di Cosenza

Cosenza, CS, Italy

Location

AOU Policlinico Vittorio Emanuele- Presidio Ospedaliero Gaspare Rodolico

Catania, CT, Italy

Location

Ospedale Nuovo Garibaldi-Nesima

Catania, CT, Italy

Location

Ospedale Vito Fazzi

Lecce, LE, 73100, Italy

Location

Ospedale Barone Romeo

Patti, ME, Italy

Location

Ospedale san Pietro Fatebenefratelli

Rome, RM, 00100, Italy

Location

Ospedale San Bortolo

Vicenza, VI, 36100, Italy

Location

SS Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

Azienda Ospedaliera Universitaria Ferrara

Ferrara, Italy

Location

Careggi

Florence, Italy

Location

Ospedali Riuniti

Foggia, Italy

Location

Ospedale San Salvatore

L’Aquila, Italy

Location

Carlo Poma

Mantova, Italy

Location

Università degli studi di Messina A.O.U. Policlinico G. Martino

Messina, Italy

Location

Mangiagalli

Milan, Italy

Location

Ospedale Niguarda

Milan, Italy

Location

A.O.U. di Modena Policlinico

Modena, Italy

Location

S. Gerardo

Monza, Italy

Location

Ospedale Maggiore

Novara, Italy

Location

Arnas Civico di Palermo

Palermo, Italy

Location

A.O. Bianchi-Melacrino-Morelli

Reggio Calabria, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, Italy

Location

Fatebenefratelli-Isola Tiberina

Roma, Italy

Location

Policlinico Gemelli-Università Cattolica S. Cuore

Rome, 00168, Italy

Location

A.O. Treviso Ospedale Cà Foncello

Treviso, Italy

Location

Belcolle

Viterbo, Italy

Location

Related Publications (28)

• Van Marter LJ, Allred EN, Pagano M, Sanocka U, Parad R, Moore M, Susser M, Paneth N, Leviton A. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network. Pediatrics. 2000 Jun;105(6):1194-201. doi: 10.1542/peds.105.6.1194.

  PMID: 10835057 RESULT

• Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008 Feb 14;358(7):700-8. doi: 10.1056/NEJMoa072788.

  PMID: 18272893 RESULT

• SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sanchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16.

  PMID: 20472939 RESULT

• Dunn MS, Kaempf J, de Klerk A, de Klerk R, Reilly M, Howard D, Ferrelli K, O'Conor J, Soll RF; Vermont Oxford Network DRM Study Group. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics. 2011 Nov;128(5):e1069-76. doi: 10.1542/peds.2010-3848. Epub 2011 Oct 24.

  PMID: 22025591 RESULT

• Dargaville PA, Aiyappan A, De Paoli AG, Dalton RG, Kuschel CA, Kamlin CO, Orsini F, Carlin JB, Davis PG. Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences. Neonatology. 2013;104(1):8-14. doi: 10.1159/000346460. Epub 2013 Apr 4.

  PMID: 23595061 RESULT

• Ammari A, Suri M, Milisavljevic V, Sahni R, Bateman D, Sanocka U, Ruzal-Shapiro C, Wung JT, Polin RA. Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Pediatr. 2005 Sep;147(3):341-7. doi: 10.1016/j.jpeds.2005.04.062.

  PMID: 16182673 RESULT

• De Jaegere AP, van der Lee JH, Cante C, van Kaam AH. Early prediction of nasal continuous positive airway pressure failure in preterm infants less than 30 weeks gestation. Acta Paediatr. 2012 Apr;101(4):374-9. doi: 10.1111/j.1651-2227.2011.02558.x. Epub 2012 Jan 9.

  PMID: 22150698 RESULT

• Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007 Oct 17;2007(4):CD003063. doi: 10.1002/14651858.CD003063.pub3.

  PMID: 17943779 RESULT

• Sandri F, Plavka R, Ancora G, Simeoni U, Stranak Z, Martinelli S, Mosca F, Nona J, Thomson M, Verder H, Fabbri L, Halliday H; CURPAP Study Group. Prophylactic or early selective surfactant combined with nCPAP in very preterm infants. Pediatrics. 2010 Jun;125(6):e1402-9. doi: 10.1542/peds.2009-2131. Epub 2010 May 3.

  PMID: 20439601 RESULT

• Brix N, Sellmer A, Jensen MS, Pedersen LV, Henriksen TB. Predictors for an unsuccessful INtubation-SURfactant-Extubation procedure: a cohort study. BMC Pediatr. 2014 Jun 19;14:155. doi: 10.1186/1471-2431-14-155.

  PMID: 24947477 RESULT

• Lakkundi A, Wright I, de Waal K. Transitional hemodynamics in preterm infants with a respiratory management strategy directed at avoidance of mechanical ventilation. Early Hum Dev. 2014 Aug;90(8):409-12. doi: 10.1016/j.earlhumdev.2014.04.017. Epub 2014 Jun 5.

  PMID: 24951077 RESULT

• Dani C, Corsini I, Bertini G, Fontanelli G, Pratesi S, Rubaltelli FF. The INSURE method in preterm infants of less than 30 weeks' gestation. J Matern Fetal Neonatal Med. 2010 Sep;23(9):1024-9. doi: 10.3109/14767050903572174.

  PMID: 20180736 RESULT

• Cherif A, Hachani C, Khrouf N. Risk factors of the failure of surfactant treatment by transient intubation during nasal continuous positive airway pressure in preterm infants. Am J Perinatol. 2008 Nov;25(10):647-52. doi: 10.1055/s-0028-1090590. Epub 2008 Oct 7.

  PMID: 18841536 RESULT

• Lista G, Boni L, Scopesi F, Mosca F, Trevisanuto D, Messner H, Vento G, Magaldi R, Del Vecchio A, Agosti M, Gizzi C, Sandri F, Biban P, Bellettato M, Gazzolo D, Boldrini A, Dani C; SLI Trial Investigators. Sustained lung inflation at birth for preterm infants: a randomized clinical trial. Pediatrics. 2015 Feb;135(2):e457-64. doi: 10.1542/peds.2014-1692.

  PMID: 25624390 RESULT

• Krause MF, Jakel C, Haberstroh J, Schulte-Monting J, Leititis JU, Orlowska-Volk M. Alveolar recruitment promotes homogeneous surfactant distribution in a piglet model of lung injury. Pediatr Res. 2001 Jul;50(1):34-43. doi: 10.1203/00006450-200107000-00009.

  PMID: 11420416 RESULT

• Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP, Guinsburg R, Hazinski MF, Morley C, Richmond S, Simon WM, Singhal N, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics. 2010 Nov;126(5):e1319-44. doi: 10.1542/peds.2010-2972B. Epub 2010 Oct 18. No abstract available.

  PMID: 20956431 RESULT

• Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Halliday HL; European Association of Perinatal Medicine. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants--2013 update. Neonatology. 2013;103(4):353-68. doi: 10.1159/000349928. Epub 2013 May 31.

  PMID: 23736015 RESULT

• Sola A, Golombek SG, Montes Bueno MT, Lemus-Varela L, Zuluaga C, Dominguez F, Baquero H, Young Sarmiento AE, Natta D, Rodriguez Perez JM, Deulofeut R, Quiroga A, Flores GL, Morgues M, Perez AG, Van Overmeire B, van Bel F. Safe oxygen saturation targeting and monitoring in preterm infants: can we avoid hypoxia and hyperoxia? Acta Paediatr. 2014 Oct;103(10):1009-18. doi: 10.1111/apa.12692. Epub 2014 Jul 28.

  PMID: 24838096 RESULT

• De Jaegere A, van Veenendaal MB, Michiels A, van Kaam AH. Lung recruitment using oxygenation during open lung high-frequency ventilation in preterm infants. Am J Respir Crit Care Med. 2006 Sep 15;174(6):639-45. doi: 10.1164/rccm.200603-351OC. Epub 2006 Jun 8.

  PMID: 16763218 RESULT

• Buzzella B, Claure N, D'Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr. 2014 Jan;164(1):46-51. doi: 10.1016/j.jpeds.2013.08.040. Epub 2013 Oct 1.

  PMID: 24094879 RESULT

• 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 RESULT

• Parry G, Tucker J, Tarnow-Mordi W; UK Neonatal Staffing Study Collaborative Group. CRIB II: an update of the clinical risk index for babies score. Lancet. 2003 May 24;361(9371):1789-91. doi: 10.1016/S0140-6736(03)13397-1.

  PMID: 12781540 RESULT

• Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978 Apr;92(4):529-34. doi: 10.1016/s0022-3476(78)80282-0.

  PMID: 305471 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Vento G, Ventura ML, Pastorino R, van Kaam AH, Carnielli V, Cools F, Dani C, Mosca F, Polglase G, Tagliabue P, Boni L, Cota F, Tana M, Tirone C, Aurilia C, Lio A, Costa S, D'Andrea V, Lucente M, Nigro G, Giordano L, Roma V, Villani PE, Fusco FP, Fasolato V, Colnaghi MR, Matassa PG, Vendettuoli V, Poggi C, Del Vecchio A, Petrillo F, Betta P, Mattia C, Garani G, Solinas A, Gitto E, Salvo V, Gargano G, Balestri E, Sandri F, Mescoli G, Martinelli S, Ilardi L, Ciarmoli E, Di Fabio S, Maranella E, Grassia C, Ausanio G, Rossi V, Motta A, Tina LG, Maiolo K, Nobile S, Messner H, Staffler A, Ferrero F, Stasi I, Pieragostini L, Mondello I, Haass C, Consigli C, Vedovato S, Grison A, Maffei G, Presta G, Perniola R, Vitaliti M, Re MP, De Curtis M, Cardilli V, Lago P, Tormena F, Orfeo L, Gizzi C, Massenzi L, Gazzolo D, Strozzi MCM, Bottino R, Pontiggia F, Berardi A, Guidotti I, Cacace C, Meli V, Quartulli L, Scorrano A, Casati A, Grappone L, Pillow JJ. Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial. Lancet Respir Med. 2021 Feb;9(2):159-166. doi: 10.1016/S2213-2600(20)30179-X. Epub 2020 Jul 17.

  PMID: 32687801 DERIVED

• Vento G, Pastorino R, Boni L, Cota F, Carnielli V, Cools F, Dani C, Mosca F, Pillow J, Polglase G, Tagliabue P, van Kaam AH, Ventura ML, Tana M, Tirone C, Aurilia C, Lio A, Ricci C, Gambacorta A, Consigli C, D'Onofrio D, Gizzi C, Massenzi L, Cardilli V, Casati A, Bottino R, Pontiggia F, Ciarmoli E, Martinelli S, Ilardi L, Colnaghi M, Matassa PG, Vendettuoli V, Villani P, Fusco F, Gazzolo D, Ricotti A, Ferrero F, Stasi I, Magaldi R, Maffei G, Presta G, Perniola R, Messina F, Montesano G, Poggi C, Giordano L, Roma E, Grassia C, Ausanio G, Sandri F, Mescoli G, Giura F, Garani G, Solinas A, Lucente M, Nigro G, Del Vecchio A, Petrillo F, Orfeo L, Grappone L, Quartulli L, Scorrano A, Messner H, Staffler A, Gargano G, Balestri E, Nobile S, Cacace C, Meli V, Dallaglio S, Pasqua B, Mattia L, Gitto E, Vitaliti M, Re MP, Vedovato S, Grison A, Berardi A, Torcetta F, Guidotti I, di Fabio S, Maranella E, Mondello I, Visentin S, Tormena F. Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial. Trials. 2016 Aug 18;17:414. doi: 10.1186/s13063-016-1498-7.

  PMID: 27538798 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Hyaline Membrane Disease

Interventions

poractant alfa; Ventilators, Mechanical; Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Equipment and Supplies; Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Giovanni Vento, MD

  Catholic University of the Sacred Heart

  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: Associate Professor

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 26, 2015
• Study Start: November 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 30, 2018
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

IT (33)