deMISTify: The Impact of Ventilator Pressure Levels During Minimally Invasive Surfactant Therapy on Lung Aeration in Preterm Infants

NCT07522346 | Not Yet Recruiting

• 1 other identifier: 123038
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Infants born preterm (before 36 weeks' gestation age) have immature lungs and struggle to breathe on their own. They are supported via respiratory machines like ventilators, as well as pharmaceutical aids like surfactant replacement therapy. Surfactant replacement therapy is an established therapy for the treatment of respiratory distress syndrome, which is a common illness in infants born preterm. Surfactant replacement therapy can be delivered to an infant's lungs a few ways, including via a small tube that is briefly placed down an infant's throat. This is considered the least invasive method currently available, and is becoming more popular. It is referred to as minimally invasive surfactant therapy (MIST). A baby can receive surfactant via MIST if they are receiving non-invasive respiratory support, like from a continuous positive airway pressure (CPAP) machine. Doctors and researchers are looking for simple ways to make MIST more effective. This clinical trial will investigate if briefly increasing the air pressure delivered by a CPAP machine before giving MIST therapy will make MIST more effective. This strategy is called a lung recruitment manoeuvre (LRM), because it opens up more of the lungs - 'recruits' them - to help with oxygenation. The CPAP setting that is briefly changed is called positive end expiratory pressure (PEEP) - it increases the amount of air left in the lungs at the end of a breath. This stops parts of the lung collapsing when exhaling, which commonly occurs in the lungs of infants born preterm as they are immature. The goal of this clinical trial is to investigate if a LRM prior to MIST improves ventilation and lung aeration in preterm infants born 24-32 weeks' gestation. The main question it aims to answer is: How a LRM prior to MIST might impact patterns of ventilation and lung aeration in preterm infants, compared to no LRM prior to MIST. The current standard of care is no LRM before MIST. Researchers will compare this current standard against a LRM before MIST to see if it potentially improves patterns of ventilation. Participants will be randomly placed (by chance) to receive either no LRM before MIST (control) or a LRM before MIST (intervention). Participants will be randomised once their treating clinical team have decided to give MIST.

Conditions

Surfactant Deficiency Syndrome Neonatal

Keywords

Minimally Invasive Surfactant Therapy; Lung Recruitment Manoeuvre; Electrical Impedance Tomography

Outcome Measures

Primary Outcomes (1)

• Mean Change in the Centre of Ventilation (ventro-dorsal)

  An electrical impedance tomography-based measure, this is a measure of the homogeneity of air distribution in the lungs along the ventral to dorsal axis. A baseline measurement will be taken pre-MIST occurring. A final measurement will be taken 60 minutes after MIST has occurred. The difference between these values will be compared as the primary outcome measure.

  Baseline, 60 minutes

Secondary Outcomes (5)

• Number of total surfactant doses

  From date of randomisation until date of discharge from primary Neonatal Intensive Care Unit, or date of death from any cause, whichever occurs first, assessed up to 12 months

• Need for intubation within 72 hours of MIST

  72 hours

• FiO2 % 24 hours after MIST

  24 hours

• Number of days on respiratory support

  From date of randomisation until date of discharge from primary Neonatal Intensive Care Unit, or date of death from any cause, whichever occurs first, assessed up to 12 months

• Incidence of air leak

  From date of randomisation until date of discharge from primary Neonatal Intensive Care Unit, or date of death from any cause, whichever occurs first, assessed up to 12 months

Study Arms (2)

Control

ACTIVE COMPARATOR

Minimally Invasive Surfactant Therapy (as per unit protocol)

Device: Control (Minimally Invasive Surfactant Therapy)

Intervention

EXPERIMENTAL

Lung recruitment manoeuvre prior to minimally invasive surfactant therapy. CPAP PEEP is increased from 7-8 cmH2O to 10 cmH2O in one step for 20 mins prior to MIST. PEEP will be decreased to 7-8 cmH2O after surfactant administration.

Device: Lung Recruitment Manoeuvre prior to Minimally Invasive Surfactant Therapy

Interventions

Lung Recruitment Manoeuvre prior to Minimally Invasive Surfactant Therapy DEVICE

Lung recruitment manoeuvre prior to minimally invasive surfactant therapy. CPAP PEEP is increased from 7-8 cmH2O to 10 cmH2O in one step for 20 mins prior to MIST. PEEP will be decreased to 7-8 cmH2O after surfactant administration.

Also known as: Lung Recruitment Manoeuvre

Intervention

Control (Minimally Invasive Surfactant Therapy) DEVICE

Minimally Invasive Surfactant Therapy (MIST) as per unit protocol

Also known as: Minimally Invasive Surfactant Therapy

Control

Eligibility Criteria

• Age: 24 Weeks - 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Born between 24 to 31+6 weeks' gestation, by best obstetric estimate
• Admitted to a participating NICU
• A parent/guardian who can provide informed consent
• Receiving CPAP respiratory support
• Planned to receive MIST by clinicians as standard clinical care
• Clinically stable (as determined by clinical team)
• Infant less than 72 hours of age
• MIST can be administered within 90 min of allocating assigned interventional arm

You may not qualify if:

• Receiving any form of respiratory support other than CPAP
• Receiving more than 8 cmH2O PEEP via CPAP in the 4 hours prior to surfactant administration (except in the Delivery Room as part of resuscitation at birth)
• The infant's clinical team has concern regarding clinical stability and tolerability of EIT
• The infant's skin integrity will not tolerate the EIT belt and gel
• Refusal of informed consent by their parent/guardian/legally acceptable representative
• The infant does not have a parent/guardian who can provide informed consent.
• Major congenital anomaly involving the cardiac, respiratory, gastrointestinal systems, or a known genetic syndrome or diagnosis that might affect respiratory course and outcomes
• Severe pulmonary hypoplasia due to anhydramnios or oligohydramnios before 24 weeks in which the neonatal clinician anticipates that pulmonary hypoplasia related respiratory failure will be the major respiratory problem in early post-natal life
• Suspected or confirmed air leak or pneumothorax
• Previous treatment with surfactant or mechanical ventilation via an endotracheal tube
• Urgent need for intubation and mechanical ventilation as determined by the treating clinician
• Not receiving full active intensive care (i.e. palliative/comfort care)

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (1)

Joan Kirner Women's and Children's Hospital

Saint Albans, Victoria, 3021, Australia

Location

Related Publications (3)

• Kidman AM, Manley BJ, Boland RA, Malhotra A, Donath SM, Beker F, Davis PG, Bhatia R. Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (ECLAT): a multicentre, randomised, superiority trial. Lancet Child Adolesc Health. 2023 Dec;7(12):844-851. doi: 10.1016/S2352-4642(23)00235-3. Epub 2023 Oct 27.

  PMID: 38240784 BACKGROUND

• Dargaville PA, Kamlin COF, Orsini F, Wang X, De Paoli AG, Kanmaz Kutman HG, Cetinkaya M, Kornhauser-Cerar L, Derrick M, Ozkan H, Hulzebos CV, Schmolzer GM, Aiyappan A, Lemyre B, Kuo S, Rajadurai VS, O'Shea J, Biniwale M, Ramanathan R, Kushnir A, Bader D, Thomas MR, Chakraborty M, Buksh MJ, Bhatia R, Sullivan CL, Shinwell ES, Dyson A, Barker DP, Kugelman A, Donovan TJ, Tauscher MK, Murthy V, Ali SKM, Yossuck P, Clark HW, Soll RF, Carlin JB, Davis PG; OPTIMIST-A Trial Investigators. Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial. JAMA. 2021 Dec 28;326(24):2478-2487. doi: 10.1001/jama.2021.21892.

  PMID: 34902013 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

MeSH Terms

Conditions

Pulmonary Atelectasis

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Study Officials

• David Tingay

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frederique N Donnelly

CONTACT

+61 8341 6200; frederique.donnelly@mcri.edu.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)