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

NCT04825197 | Unknown Phase 2 DMC

• 1 other identifier: 3435
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bronchopulmonary Dysplasia; Chronic Pulmonary Insufficiency of Prematurity

Keywords

surfactant; preterm; recruitment; bronchopulmonary dysplasia; hfov

Outcome Measures

Primary Outcomes (1)

• First successful extubation

  The time to first successful extubation ( expressed as day of life).

  From date of randomization until the date of first documented progression, assessed up to 40 weeks of post menstrual age

Secondary Outcomes (13)

• Rate of Bronchopulmonary dysplasia

  At 36 weeks of post-menstrual age

• Rate of Interstitial emphysema

  In the 21 days following experimental treatment

• Rate of Pneumothorax

  In the 21 days following experimental treatment

• Rate of Pulmonary haemorrhage

  In the 21 days following experimental treatment

• Rate of Necrotising enterocolitis

  Up to 40 weeks post-mestrual age

Study Arms (2)

LRS Group

EXPERIMENTAL

This arm will receive up to 4 doses (100 mg Kg) of Poractant alfa (Curosurf, Chiesi) every 12 hours; each dose preceded by a recruitment manoeuvre in HFOV. Optimal recruitment is defined as adequate oxygenation using a fraction of inspired oxygen (FiO2) of 0.30 or less. The continuous distending pressure (CDP) will be increased stepwise (1 cmH2O every 2-3 min) as long as pulse oximetry (SpO2) improves. The FiO2 will be reduced stepwise, keeping SpO2 within the target range (87-94 %). The recruitment procedure will be stopped if oxygenation no longer improves or if the FiO2 is equal to or less than 0.30. The corresponding CDP will be called the opening pressure (CDPO). Next, the CDP will be reduced stepwise (1-2 cmH2O every 2-3 min) until the SpO2 deteriorates (by at least 2-3 points). The corresponding CDP will be called the closing pressure (CDPC). After a second recruitment maneuver at CDPO for 5 min, the optimal CDP (CDPOPT) will be set 2 cmH2O above the CDPC for at least 3 min.

Drug: Poractant Alfa Intratracheal Suspension [Curosurf]

Standard Group

NO INTERVENTION

This arm will be managed following the ward standard ventilatory protocol which does not contemplate neither surfactant administration nor recruitment manoeuvre.

Interventions

Poractant Alfa Intratracheal Suspension [Curosurf] DRUG

up to 4 doses (100 mg Kg) of Poractant alfa every 12 hours; each dose preceded by a recruitment manoeuvre in HFOV.

Also known as: Surfactant endotracheal administration following a recruitment HFOV manoeuvre

LRS Group

Eligibility Criteria

• Age: 7 Days - 10 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. Extremely low gestational age newborn infants (GA \< 28 weeks) - gestational age matching between maternal dates and/or early antenatal ultrasound
• \. Singleton or multiple birth
• \. Postnatal age between 7 and 10 days
• \. Invasive mechanical ventilation still needed
• \. Fraction of inspired oxygen (FiO2) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours
• \. Stable cardiovascular condition
• \. Informed consent form signed by parents or legal guardian

You may not qualify if:

• \. Major congenital malformation (i.e., infants with genetic, metabolic or endocrine disorder diagnosed before enrolment)
• \. High index of suspicion of infection before enrolment
• \. Neurological conditions that might contraindicate extubation
• \. Inotropic agents needed
• \. Pneumothorax
• \. Hemodynamically significant ductus arteriosus
• \. Surgical intervention within the past 72 hours
• \. Partecipation in another interventional clinical study that may interfere with the results of this trial
• \. Known hypersensitivity to the drug or to one of the excipients

Sponsors & Collaborators

• VENTO GIOVANNI: lead

Study Sites (1)

Fondazione Policlinico Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Related Publications (8)

• 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.

  PMID: 30460252 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.

  PMID: 17622950 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.

  PMID: 15496605 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.

  PMID: 26928567 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.

  PMID: 26500107 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.

  PMID: 31498776 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.

  PMID: 32687801 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.

  PMID: 29389921 BACKGROUND

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth

Interventions

poractant alfa

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Giovanni Vento, Professor

  Fondazione Policlinico Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giovanni Vento, Professor

CONTACT

00390630153237; giovanni.vento@unicatt.it

Alessandra Lio, MD

CONTACT

alessandra.lio@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 1, 2021
• Study Start: December 1, 2021
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2025
• Last Updated: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 6 months following article publication.
• Access Criteria: All researchers who provide a methodologically sound proposal will have access to data. Proposals should be directed to giovanni.vento@unicatt.it.

Locations

IT (1)