LISA in the Delivery Room for Extremely Preterm Infants (DRLISA)

Less Invasive Administration of Surfactant in the Delivery Room for Extremely Preterm Infants: A Randomized Control Trial

The purpose of this study is to evaluate the effect of LISA used in the delivery room (DR) in decreasing the intubation rates in preterm infants at 22-25 weeks gestational age (GA), during first 72 hours compared to the standard approach of stabilization on nasal CPAP in the DR and administering surfactant in the NICU.

Infants in both groups will be resuscitated per NRP algorithm. Infants who maintain a stable HR and respiratory effort on CPAP will qualify for the intervention. Infants in Group 1 (Intervention arm) will receive LISA in DR. CPAP will be titrated between 5-8 cm H20 after LISA. Infants in Group 2 (Control arm) will be transferred to NICU on CPAP. The CPAP level will be increased stepwise every 30 minutes to 7 cm H2O if FiO2 ≥0.3. Infants requiring CPAP 7 at FiO2 ≥0.3 will receive LISA. CPAP will be titrated between 5-8 cm H20 after LISA.

Infants in both arms requiring CPAP 7 and FiO2 >0.8 at 20 MOL in the delivery room will be intubated in DR. Any infant with a heart rate not responding with appropriate PPV will be intubated in the DR. CXR will be obtain on admission and umbilical lines will be placed. Infants in both arm who require FiO2 ≥0.6 for ≥1 hour, apnea requiring stimulation 3 times within one hour or ≥6 over 6 hour period, any apnea requiring PPV, or CO2 >0.65 in two consecutive blood gases drawn over two hours will be considered as reasons for intubation after LISA.

Primary outcome is the need for MV within 72 hours of life, secondary outcome includes need for MV during first week of life and during hospital stay, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), need for treatment of patent ductus arteriosus (PDA), composite death or BPD and mortality. This is a feasibility trial with the intention to enroll 30 infants in each arm of the study over three years.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Distress Syndrome; Extreme Prematurity
• Intervention / Treatment: Procedure: LISA

Detailed Description

This is a single center, unblinded, randomized control, feasibility trial to evaluate the use of LISA in the DR for extremely preterm infants born 22-25 weeks GA who were successfully resuscitated without being intubated. The study team will approach a mother who is at risk of delivering an infant between 22-25 week GA for consent to be included in the study. Infants will be resuscitated according to NRP algorithm. Infants who are successfully resuscitated without requiring intubation and mechanical ventilation (HR >100, regular spontaneous respiratory effort, able to maintain oxygenation per NRP target saturation goal) are eligible for enrollment. Randomization will be achieved by opening an opaque envelope.

• Intervention arm (DR-LISA): Infants with a stable heart rate and spontaneous respiratory effort on CPAP are eligible for surfactant therapy. A LISA catheter will be prepared for use prior to the birth of the infant. Surfactant will be drawn into a syringe soon after the initial stabilization. A trained physician will perform LISA. The infant will be maintained on CPAP by prongs during the procedure. PPV will be provided if needed after the procedure. The infant will be monitored in the DR for stable HR, respiration and SpO2 prior to being moved to a transporter. Infants requiring FiO2 >0.8 on CPAP 8 cm H2O to maintain SpO2 88-94% by 20 minutes of life will be intubated prior to transport. After admission to NICU, CPAP level will be titrated between 5-8 cm H20 based on FiO2 threshold ≥0.3
• Control arm: Infants will be resuscitated per NRP guidelines. Infant with stable HR and respiratory effort will be changed to binasal prongs and transported to NICU on CPAP. CPAP level be titrated between 5- 7 cm H2O in the DR. Infants requiring FiO2 >0.8 to maintain SpO2 88-94% by 20 minutes of life will be intubated in DR. After admission to NICU, CPAP will be escalated every 30 minutes up to a maximum level of 7 cm H2O at which point infant would qualify for LISA if the FiO2 requirement is ≥0.3. CPAP level will be titrated between 5-8 cm H20 based on FiO2 threshold ≥0.3. Infants in both groups who require FiO2 ≥0.6 for ≥1 hour, apnea requiring stimulation 3 times within one hour or ≥6 over 6 hour period, any apnea requiring PPV, or CO2 >0.65 in two consecutive blood gases drawn over two hours will be considered as reasons for intubation after LISA.

Repeat doses of surfactant will be administered every 12 hours for FiO2 ≥0.4 up to a maximum of three doses.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Venkatakrishna Kakkilaya, MBBS; Phone Number: 2146483903; Email: Venkat.Kakkilaya@UTSouthwestern.edu
• Study Contact Backup: Name: Christina M Chan, MD; Phone Number: 2146483903; Email: Christina.Chan@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75093
      • Recruiting
      • Venkatakrishna Kakkilaya
      • Contact: Venkatakrishna Kakkilaya; Phone Number: 214-648-3903; Email: venkat.kakkilaya@utsouthwestern.edu
      • Principal Investigator: Venkatakrishna Kakkilaya, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 minutes to 20 minutes (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants born 22 -25 weeks GA
• Resuscitated without requiring intubation and maintaining HR >100, oxygen saturation per NRP goal saturation limits and regular respiratory effort on CPAP

Exclusion Criteria:

• Major congenital anomalies

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DR-LISA; Experimental: Infants will be resuscitated per NRP guidelines. Infant with stable HR and respiratory effort will be changed to binasal prongs. A trained physician will perform LISA using Hobart method. Infants requiring FiO2 >0.8 on CPAP 8 cm H2O to maintain SpO2 88-94% by 20 minutes of life will be intubated prior to transport. After admission to the NICU, CPAP will be titrated 5-8 cm H20.	Procedure: LISA; LISA administered in the DR after initial resuscitation or in the NICU after stepwise escalation of CPAP based on FiO2 ≥0.3. While maintaining infant on CPAP with binasal prongs/small nasal mask, a thin catheter (Hobart method) is inserted below the vocal cord using direct laryngoscopy. Poractant alfa (200mg/kg) is administered slowly over 2-3 minutes. Catheter is then withdrawn and infant is maintained on CPAP
Active Comparator: NICU-LISA; Infants will be resuscitated per NRP guidelines. Infant with stable HR and respiratory effort will be changed to binasal prongs and transported to NICU on CPAP. After admission to NICU, CPAP will be escalated every 30 minutes up to a maximum level of 7 cm H2O at which point infant would qualify for LISA if the FiO2 requirement is ≥0.3. LISA will be performed using Hobart method. Infants requiring FiO2 >0.8 to maintain SpO2 88-94% by 20 minutes of life will be intubated in the DR.	Procedure: LISA; LISA administered in the DR after initial resuscitation or in the NICU after stepwise escalation of CPAP based on FiO2 ≥0.3. While maintaining infant on CPAP with binasal prongs/small nasal mask, a thin catheter (Hobart method) is inserted below the vocal cord using direct laryngoscopy. Poractant alfa (200mg/kg) is administered slowly over 2-3 minutes. Catheter is then withdrawn and infant is maintained on CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for intubation and/any mechanical ventilation	Any Infant randomized to the study requiring intubation and/mechanical ventilation	within 72 hours of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for mechanical ventilation within 7 days of life	Any Infant randomized to the study requiring intubation and/mechanical ventilation	Within 7 days of life.
Mechanical Ventilation	Any infant requiring MV	Until hospital discharge or 6 months of life
High Frequency Ventilation	Any infant requiring high frequency ventilation	Until hospital discharge or 6 months of life
Mechanical ventilator days	Infant requiring MV for longer than 12 hours in a day	Until hospital discharge or 6 months of life
Bronchopulmonary dysplasia	Infant requiring supplemental oxygen at 36 weeks PMA	Until hospital discharge or 6 months of life
Severe intraventricular hemorrhage	Grade 3 or 4 intraventricular hemorrhage	Until hospital discharge or 6 months of life
Pneumothorax	Radiographic evidence of pneumothorax	Until hospital discharge or 6 months of life
Desaturation (SpO2 <80) and Bradycardia (HR <100) events	Any desaturation and bradycardia event lasting >10 seconds during LISA procedure	During the first 72 hours
Proportion of infants requiring >1 LISA attempt	Any direct laryngoscopy attempt	During the first 72 hours of life

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Chiesi USA, Inc.
• Investigators: Principal Investigator: Venkatakrishna Kakkilaya, MBBS, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Estimated): June 29, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 16, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: STU-2020-0926

Drug and device information, study documents

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