LISA vs Endotracheal Surfactant in Preterm Neonates: A Lung Ultrasound Distribution Study (LISA-Ven-LUS)

A Prospective Pilot Controlled Trial Comparing the Intrapulmonary Distribution of Exogenous Surfactant Between (LISA) and Conventional Endotracheal Intubation in Preterm Neonates With RDS Using Lung Ultrasound and the NOVEL Surfactant Distribution Homogeneity Index (SDHI)

This prospective, non-randomized, unblinded pilot study evaluates and compares the intrapulmonary distribution of exogenous surfactant in preterm neonates when administered via Less Invasive Surfactant Administration (LISA) versus conventional endotracheal intubation (ETT). Lung ultrasound (LUS) will be utilized to assess the pioneer Surfactant Distribution Homogeneity Index (SDHI) to quantify the evenness and extent of surfactant-induced lung aeration. Secondary objectives include evaluating changes in LUS scores, short-term clinical respiratory outcomes, and feasibility parameters for guiding future larger-scale trials.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Distress Syndrome, Newborn
• Intervention / Treatment: Procedure: surfactant administration by thin catheter; Procedure: surfactant administration by ETT

Detailed Description

Respiratory Distress Syndrome (RDS) is a primary cause of neonatal morbidity, typically managed with exogenous surfactant. While LISA has emerged as a preferred method to avoid mechanical ventilation, the comparative homogeneity of surfactant distribution remains unclear. This pilot study enrolls 22 infants (1:1 allocation) in a tertiary-level Neonatal Intensive Care Unit (NICU). The experimental group receives surfactant via a thin catheter while on non-invasive support, whereas the active comparator group receives surfactant via an endotracheal tube. High-frequency linear probe lung ultrasounds are performed immediately before and 60 minutes post-administration across 12 lung regions. The primary metric, the genuine Surfactant Distribution Homogeneity Index (SDHI), is calculated from regional LUS score changes to assess aeration uniformity.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Loay A Alkamel, MD, Mac; Phone Number: 0097455190326; Email: lalkamel@hamad.qa

Study Locations

• Qatar
  • Doha, Qatar
    • Recruiting
    • Women's Wellness and Research Center (WWRC), Hamad Medical Corporation
    • Contact: Loay A Alkamel, MD, Msc; Phone Number: 0097455190326; Email: loay.alkamel@gmail.com
    • Sub-Investigator: Husam Salameh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Gestational age 24+0 to 42+6 weeks. Clinical and radiographic diagnosis of Respiratory Distress Syndrome (RDS). Requirement for surfactant within the first 3 days of life. Written informed parental consent.

Exclusion Criteria:

Infants intubated at birth or who received surfactant prophylactically in the delivery room.

Major congenital anomalies or lung malformations (e.g., congenital diaphragmatic hernia, pulmonary hypoplasia).

Syndromic or genetic conditions affecting lung or chest wall development. Severe hemodynamic instability or congenital heart disease requiring intensive support.

Lack of parental consent for trial participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1: LISA Group; Administration of exogenous surfactant (Beractant, 100 mg/kg in 4 mL/kg) via a thin catheter while the infant is maintained on non-invasive respiratory support (CPAP or NIPPV).	Procedure: surfactant administration by thin catheter; Administration of exogenous surfactant (Beractant, 100 mg/kg in 4 mL/kg) via a thin catheter while the infant is maintained on non-invasive respiratory support (CPAP or NIPPV).; Other Names: LISA
Experimental: ETT Group; Administration of exogenous surfactant (Beractant, 100 mg/kg in 4 mL/kg) delivered via an endotracheal tube following intubation, accompanied by brief mechanical ventilation and extubation if feasible.	Procedure: surfactant administration by ETT; Administration of exogenous surfactant (Beractant, 100 mg/kg in 4 mL/kg) via an endotracheal tube following intubation, accompanied by brief mechanical ventilation and extubation if feasible.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surfactant Distribution Homogeneity Index (SDHI) Derived from Lung Ultrasound Imaging scores pre and at 60 Minutes Post-Surfactant Administration.	A novel metric calculated from the change in regional Lung Ultrasound (LUS) scores before and after surfactant administration. The(SDHI) quantifies the uniformity of surfactant distribution across lung regions. The SDHI will be calculated 1 hour after surfactant administration. A higher SDHI is hypothesised to indicate more homogeneous distribution of surfactant across the lungs. Each infant will have a single SDHI value post-intervention, and this will be compared between the LISA and ETT groups to evaluate whether one administration method achieves superior surfactant distribution homogeneity. The SDHI evaluates the homogeneity of surfactant distribution using multiple formulations applied to regional LUS score changes across 12 predefined lung regions (anterior, lateral, and posterior zones for both left and right hemithoraces). The computation involves comparing regional LUS improvements SDHI (dimensionless index); higher values indicate more homogeneous surfactant distribution	Baseline (immediately before administration) and 60 minutes (+/- 15 min) post-administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Lung Ultrasound Score (LUS) from Baseline to 60 Minutes Post-Surfactant Administration	The Lung Ultrasound Scoring System (LUSS) will be used to quantify lung aeration. Each of 12 predefined lung regions (anterior, lateral, and posterior zones for both left and right hemithoraces) will be scored on a scale from 0 to 3, where: 0 = normal aeration (no B-lines), 1 = moderate aeration (B-lines <50% of region), 2 = poor aeration (B-lines ≥50% of region), and 3 = consolidation. Higher scores indicate worse aeration. Total LUS score ranges from 0 (best) to 36 (worst). Regional changes will be analyzed by anatomical zone (anterior-posterior, left-right) to assess distribution homogeneity. The primary analysis will report the mean change in total LUS score and regional LUS scores for each study arm, with comparison between LISA and ETT groups. Scale Name (Unabbreviated): Lung Ultrasound Scoring System (LUSS) Minimum Value: 0 Maximum Value: 36 Higher Scores Indicate: Worse aeration (lower is better outcome)	Baseline and 60 minutes post-administration.
Number of Participants Requiring Invasive Mechanical Ventilation Following Initial Surfactant Administration	The proportion of infants in each arm (LISA vs. ETT) who require intubation and invasive mechanical ventilation after the initial surfactant dose. This is a binary outcome (yes/no) and will be reported as the number and percentage of participants in each arm requiring mechanical ventilation. Mechanical ventilation is defined as the need for endotracheal intubation with positive pressure ventilation support. The analysis will compare the rate of mechanical ventilation requirement between the two study groups to evaluate whether LISA reduces the need for invasive ventilation compared to standard ETT administration. Measurement Unit Count and percentage of participants (0-22 participants per arm)	Within 72 hours post-intervention.
Number of Participants Requiring a Second Dose of Surfactant Due to Persistent Respiratory Distress Syndrome	The proportion of infants in each arm (LISA vs. ETT) who require a second dose of exogenous surfactant due to persistent or worsening radiographic and clinical evidence of Respiratory Distress Syndrome (RDS). This is a binary outcome (yes/no) and will be reported as the number and percentage of participants in each arm requiring repeat surfactant dosing. Repeat dosing is determined by the clinical team based on persistent RDS criteria, including radiographic findings and clinical respiratory severity. The analysis will compare the rate of repeat surfactant requirement between the two study groups to evaluate the efficacy of each administration method in providing adequate initial surfactant distribution. Measurement Unit Count and percentage of participants (0-22 participants per arm)	Up to 72 hours of life.

Collaborators and Investigators

• Sponsor: Hamad General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Less Invasive Surfactant Administration, LISA, Lung Ultrasound, Neonatology, Surfactant Distribution Homogeneity Index
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Respiratory Distress Syndrome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: MRC-01-25-899 Abhath-HMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No