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RecruitingNCT07271368ENCP LISAUpdated Aug 21, 2026

EXTERNAL NEGATIVE PRESSURE DURING LISA

An interventional study of ENCP in Neonatology, sponsored by Charles University, Czech Republic. Recruiting at 1 site in Czechia. Open to participants aged 1 Hour to 3 Days. Per ClinicalTrials.gov, last updated 2026-08-21.

Sponsored by Charles University, Czech Republic · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
1 Hour to 3 Days
Sex
All
01

Study summary

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

Read the 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

02

Conditions studied

  • Neonatology

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Keywords

  • LISA, negative pressure, neonatology, preterm, surfactant
03

Who can participate

Ages eligible
1 Hour to 3 Days
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
25 participants (estimated)

Study arms

  • Experimental
    ENCP LISA

    Infants will remain on CPAP (6-8 cm H₂O) or HFNC (8 L/min) with FiO₂ titrated to maintain SpO₂ ≥92%. LISA catheter will be introduced under direct laryngoscopic vision 1-2 cm below the vocal cords. Two fractional boluses of surfactant (Curosurf, 200 mg/kg) will be administered within 2 minutes during ECNP support using Hayek RTX via a well-fitted thoracoabdominal cuirass. ECNP will be maintained at -10 cmH₂O throughout administration and for 10 minutes after. FiO₂ will not be reduced until SpO₂ stabilizes ≥92% and FiO₂ is ≤0.25.

    Procedure: ENCP

Interventions

  • ProcedureENCP

    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.

05

What researchers measure

Primary outcomes

  1. Safety of the procedure

    No more than 20% of neonates experience serious adverse events requiring procedural interruption. Serious adverse events: * apnea necessitating positive pressure ventilation (PPV) or intubation * persistent desaturation (SpO₂ \< 80%) unresponsive to increased FiO₂ * prolonged bradycardia (heart rate \< 100 bpm) requiring interruption of the procedure * any other adverse event or treatment failure leading to the need for a repeated surfactant administration.

    Time frame: 15 minutes

Secondary outcomes

  1. Completion of the LISA procedure without interruption

    Completion of the LISA procedure without interruption due to desaturation, bradycardia, or apnea, and reduction of FiO₂ to ≤0.25 within 3 hours after surfactant administration.

    Time frame: 3 hours

06

Study locations

1 of 1 sites recruiting
  • Klinika gynekologie, porodnictví a neonatologie
    Prague, Praha 2 128 08, Czechia
    Recruiting
07

References and documents

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. PubMed 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.2015.0504. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 18183564 ↗
  • Mohammadizadeh M, Ardestani AG, Sadeghnia AR. Early administration of surfactant via a thin intratracheal catheter in preterm infants with respiratory distress syndrome: Feasibility and outcome. J Res Pharm Pract. 2015 Jan-Mar;4(1):31-6. doi: 10.4103/2279-042X.150053. PubMed 25710048 ↗
  • Teare MD, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters SJ. Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014 Jul 3;15:264. doi: 10.1186/1745-6215-15-264. PubMed 24993581 ↗
  • Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016 Jun;25(3):1057-73. doi: 10.1177/0962280215588241. Epub 2015 Jun 19. PubMed 26092476 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT07271368
Lead sponsor
Charles University, Czech Republic
Responsible party
Ján Hlivák (Principal investigator, Charles University, Czech Republic) — Principal investigator
First posted
Dec 9, 2025
Start date
Mar 17, 2025
Primary completion
Mar 30, 2027 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Aug 21, 2026

Study contacts

Ján Hlivák, MUDr.
Contact
jan.hlivak@vfn.cz
+420774221805
Tereza Lamberská, MUDr., PhD.
Contact
tereza.lamberska@vfn.cz
+420224967404

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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