EXTERNAL NEGATIVE PRESSURE DURING LISA

Official title

AN EXTERNAL NEGATIVE PRESSURE USE DURING THE LISA PROCEDURE. A FEASIBILITY STUDY

Overview

The goal of this clinical trial is to evaluate the feasibility, safety, and preliminary effectiveness of applying external continuous negative pressure (ECNP) during less invasive surfactant administration (LISA) in preterm infants with respiratory distress syndrome (RDS). It will also assess whether ECNP can improve surfactant distribution and reduce procedural complications. The main questions it aims to answer are: Does ECNP during LISA improve surfactant distribution and oxygenation in preterm infants with RDS? Does ECNP reduce the occurrence of complications such as desaturation, bradycardia, or apnea during the procedure? Does ECNP reduce the need for repeated surfactant administration? Researchers will evaluate ECNP combined with LISA in preterm infants on HFNC or CPAP to see if it improves outcomes compared to standard methods. Participants will: Receive LISA with ECNP support via a soft thoracoabdominal cuirass Be monitored for procedural complications like desaturation, bradycardia, or apnea Have their oxygenation levels, surfactant distribution, and need for repeated surfactant doses assessed Primary Outcome: The procedure will be considered safe if no more than 20% of participants experience serious adverse events, such as apnea requiring positive pressure ventilation or persistent desaturation. Secondary Outcomes: Completion of LISA without interruption due to complications Reduction of FiO₂ to ≤0.25 within 3 hours post-surfactant administration Avoidance of repeated surfactant doses via the INSURE method

Detailed description

This pilot study evaluates the feasibility, safety, and preliminary effectiveness of applying external continuous negative pressure (ECNP) during less invasive surfactant administration (LISA) in preterm infants with respiratory distress syndrome (RDS) supported by non-invasive respiratory support. ECNP, delivered via a modern negative-pressure ventilation device and a soft thoracoabdominal cuirass, generates a sustained sub-atmospheric pressure around the chest wall. This mode of support is intended to facilitate spontaneous breathing, promote more homogeneous lung inflation, and potentially enhance the distribution of intratracheally delivered surfactant.

LISA using thin catheters is a widely adopted method for surfactant administration in spontaneously breathing neonates receiving CPAP or HFNC. Although effective, the procedure is frequently complicated by transient hypoxemia, bradycardia, apnea, and surfactant reflux, occasionally requiring temporary interruption or conversion to more invasive therapy. These complications may impair surfactant delivery, contribute to uneven lung aeration, and lead to the need for repeated dosing. To date, the integration of continuous negative-pressure support during LISA has not been evaluated in clinical practice.

In this single-arm feasibility study, ECNP will be initiated shortly before and maintained throughout the LISA procedure. The study will assess whether negative-pressure support stabilizes spontaneous ventilation, improves oxygenation, and facilitates more uniform surfactant distribution during administration. Safety will be evaluated based on the occurrence of serious procedure-related events requiring interruption, such as significant desaturation, bradycardia, or apnea requiring positive-pressure ventilation. Effectiveness will be explored through measures of post-procedure oxygenation stability, need for repeat surfactant dosing, and indicators of adequate surfactant distribution (e.g., imaging assessments when clinically indicated).

This exploratory study is designed to inform the potential utility of ECNP as an adjunct during LISA and to determine whether a larger controlled trial is warranted. The protocol focuses on documenting feasibility (ability to complete LISA under ECNP), characterizing physiologic responses, and capturing any adverse events specifically associated with ECNP use in this population

Interventions

• Procedure ENCP
  Surfactant will be given in two doses within 2 minutes while continuous negative pressure is applied using the Hayek RTX thoracoabdominal cuirass. Negative pressure will be maintained during and for 10 minutes after administration.

Primary outcome measures

• Safety of the procedure [Time frame: 15 minutes]

Secondary outcome measures (1)

• Completion of the LISA procedure without interruption [Time frame: 3 hours]

Eligibility criteria

Inclusion criteria

• Preterm infants ≥ 32 weeks of gestational age
• FiO₂ > 0.30 for more than 30 minutes on CPAP (6 - 8 cm H₂O) or HFNC (8 l/min)
• Increased work of breathing despite FiO₂ < 0.30
• Birth weight > 800 g
• X-ray confirmed RDS
• Availability of all required devices and appropriately fitting cuirass

Exclusion criteria

• Requirement for endotracheal intubation or mechanical ventilation prior to surfactant administration
• Major congenital anomalies (cardiac, pulmonary, chromosomal)
• Known or suspected neuromuscular or metabolic disorders
• Lack or withdrawal of informed parental consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Deep A, De Munter C, Desai A. Negative pressure ventilation in pediatric critical care setting. Indian J Pediatr. 2007 May;74(5):483-8. doi: 10.1007/s12098-007-0082-2. PMID 17526961
• Kribs A, Roll C, Gopel W, Wieg C, Groneck P, Laux R, Teig N, Hoehn T, Bohm W, Welzing L, Vochem M, Hoppenz M, Buhrer C, Mehler K, Stutzer H, Franklin J, Stohr A, Herting E, Roth B; NINSAPP Trial Investigators. Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2015 Aug;169(8):723-30. doi: 10.1001/jamapediatrics.2015. PMID 26053341
• Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2017 Jan;102(1):F17-F23. doi: 10.1136/archdischild-2015-310299. Epub 2016 Nov 15. PMID 27852668
• Dargaville PA, Aiyappan A, Cornelius A, Williams C, De Paoli AG. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Arch Dis Child Fetal Neonatal Ed. 2011 Jul;96(4):F243-8. doi: 10.1136/adc.2010.192518. Epub 2010 Oct 21. PMID 20971722
• Roberts CT, Halibullah I, Bhatia R, Green EA, Kamlin COF, Davis PG, Manley BJ. Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units. J Pediatr. 2021 Feb;229:141-146. doi: 10.1016/j.jpeds.2020.10.025. Epub 2020 Oct 14. PMID 33068569
• Dargaville PA, Ali SKM, Jackson HD, Williams C, De Paoli AG. Impact of Minimally Invasive Surfactant Therapy in Preterm Infants at 29-32 Weeks Gestation. Neonatology. 2018;113(1):7-14. doi: 10.1159/000480066. Epub 2017 Sep 19. PMID 28922658
• Kurepa D, Perveen S, Lipener Y, Kakkilaya V. The use of less invasive surfactant administration (LISA) in the United States with review of the literature. J Perinatol. 2019 Mar;39(3):426-432. doi: 10.1038/s41372-018-0302-9. Epub 2019 Jan 11. PMID 30635595
• Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008 Apr;31(2):180-91. doi: 10.1002/nur.20247. PMID 18183564

Identifiers

NCT: NCT07271368 · 117/25 S-IV AP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗