Late Surfactant After a Recruitment Maneuver in Extremely Low Gestational Age Newborns - LATE-REC-SURF Trial

Summary

This is an unblinded monocentric pilot superiority trial that will be conducted in a IIIlevel NICU at Fondazione Policlinico Agostino Gemelli - IRCCS. The aim of the study is to test the hypothesis that endotracheal administration of poractant alfa preceded by a recruitment manoeuvre in High-Frequency Oscillatory Ventilation (HFOV) modality in preterm infants still requiring mechanical ventilation at 7-10 days of life could reduce the length of invasive mechanical ventilation. Extremely low gestational age newborn infants (GA \< 28 weeks) still requiring invasive mechanical ventilation at a postnatal age between 7 and 10 days will be eligible for the study. The study population will be randomly assigned to experimental protocol or to standard care. Treatment group will receive up to 4 doses (100 mg Kg) of Poractant alfa every 12 hours; each dose will be preceded by a recruitment manoeuvre in HFOV. Primary endpoint will be the first successful extubation defined as extubation not followed by a reintubation for at least 7 days. Several secondary endpoints will be collected, including respiratory status at one year of age.

Timeline

Start

2021-12-01

Primary completion

2023-02-01

Completion

2025-02-01

Publications

• Background Bates JHT, Smith BJ. Ventilator-induced lung injury and lung mechanics. Ann Transl Med. 2018 Oct;6(19):378. doi: 10.21037/atm.2018.06.29.
• Background Digeronimo RJ, Mustafa SB, Ryan RM, Sternberg ZZ, Ashton DJ, Seidner SR. Mechanical ventilation down-regulates surfactant protein A and keratinocyte growth factor expression in premature rabbits. Pediatr Res. 2007 Sep;62(3):277-82. doi: 10.1203/PDR.0b013e3181256aeb.
• Background Merrill JD, Ballard RA, Cnaan A, Hibbs AM, Godinez RI, Godinez MH, Truog WE, Ballard PL. Dysfunction of pulmonary surfactant in chronically ventilated premature infants. Pediatr Res. 2004 Dec;56(6):918-26. doi: 10.1203/01.PDR.0000145565.45490.D9. Epub 2004 Oct 20.
• Background Hascoet JM, Picaud JC, Ligi I, Blanc T, Moreau F, Pinturier MF, Zupan V, Guilhoto I, Hamon IR, Alexandre C, Bouissou A, Storme L, Patkai J, Pomedio M, Rouabah M, Coletto L, Vieux R. Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age: A Randomized Clinical Trial. JAMA Pediatr. 2016 Apr;170(4):365-72. doi: 10.1001/jamapediatrics.2015.4617.
• Background Ballard RA, Keller RL, Black DM, Ballard PL, Merrill JD, Eichenwald EC, Truog WE, Mammel MC, Steinhorn RH, Rogers EE, Ryan RM, Durand DJ, Asselin JM, Bendel CM, Bendel-Stenzel EM, Courtney SE, Dhanireddy R, Hudak ML, Koch FR, Mayock DE, McKay VJ, O'Shea TM, Porta NF, Wadhawan R, Palermo L; TOLSURF Study Group. Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide. J Pediatr. 2016 Jan;168:23-29.e4. doi: 10.1016/j.jpeds.2015.09.031. Epub 2015 Oct 21.
• Background Tingay DG, Togo A, Pereira-Fantini PM, Miedema M, McCall KE, Perkins EJ, Thomson J, Dowse G, Sourial M, Dellaca RL, Davis PG, Dargaville PA. Aeration strategy at birth influences the physiological response to surfactant in preterm lambs. Arch Dis Child Fetal Neonatal Ed. 2019 Nov;104(6):F587-F593. doi: 10.1136/archdischild-2018-316240. Epub 2019 Feb 1.
• Background 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.
• Background Shalish W, Kanbar L, Keszler M, Chawla S, Kovacs L, Rao S, Panaitescu BA, Laliberte A, Precup D, Brown K, Kearney RE, Sant'Anna GM. Patterns of reintubation in extremely preterm infants: a longitudinal cohort study. Pediatr Res. 2018 May;83(5):969-975. doi: 10.1038/pr.2017.330. Epub 2018 Jan 31.

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Indications