EXTERNAL NEGATIVE PRESSURE DURING LISA

NCT ID: NCT07271368

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-22

Study Completion Date

2027-01-31

Brief Summary

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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

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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

Conditions

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Neonatology

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

ENCP

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

1 Hour

Maximum Eligible Age

3 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Charles University, Czech Republic

OTHER

Sponsor Role lead

Responsible Party

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Ján Hlivák

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Ján Hlivák, MUDr.

Role: CONTACT

+420774221805

Tereza Lamberská, MUDr., PhD.

Role: CONTACT

+420224967404

References

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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.

Reference Type BACKGROUND
PMID: 17526961 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26053341 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27852668 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
PMID: 33068569 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28922658 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30635595 (View on PubMed)

Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008 Apr;31(2):180-91. doi: 10.1002/nur.20247.

Reference Type BACKGROUND
PMID: 18183564 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25710048 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24993581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26092476 (View on PubMed)

Other Identifiers

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117/25 S-IV AP

Identifier Type: -

Identifier Source: org_study_id