Early Caffeine and LISA Compared to Caffeine and CPAP in Preterm Infants

NCT04209946 | Completed DMC

• 1 other identifier: CaLI
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

Brief Summary

This study is being conducted to determine whether prophylactic administration of surfactant by the Less Invasive Surfactant Administration (LISA) method reduces the need for mechanical ventilation in the first 72 hours of life when compared to early Continuous Positive Airway Pressure (CPAP) alone.

Conditions

Premature Lungs; Respiratory Distress Syndrome; Surfactant Deficiency Syndrome Neonatal

Keywords

Premature Infants; Respiratory Distress Syndrome; Less Invasive Surfactant administration; Continuous Positive Airway Pressure (CPAP)

Outcome Measures

Primary Outcomes (1)

• Frequency of subjects requiring endotracheal intubation between the two groups (LISA vs CPAP) in the first 72 hours of life

  Required intubation or meeting respiratory failure criteria of having a pCO2 greater than 65 mm Hg or an FiO2 greater than 0.4 for more than 2 hours in the first 72 hours of life

  Within 72 hours of life

Secondary Outcomes (6)

• Duration of mechanical ventilation and/or CPAP

  Through study completion at discharge, up to 6 months of corrected gestational age

• Oxygen at 36 weeks corrected age

  Up to 40 weeks of corrected gestational age

• Frequency of Grade III and IV intraventricular hemorrhage

  Through study completion at discharge, up to 6 months of corrected gestational age

• Neurodevelopment outcome at 24 months of corrected gestational age

  Up to 2 years of corrected gestational age

• Neurodevelopment outcome at 2 Years of Age

  22-26 months corrected gestational age

Other Outcomes (2)

• Laryngoscopy attempt with the LISA procedure

  Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age

• Laryngoscopy attempt with endotracheal intubation

  Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age

Study Arms (2)

Less Invasive Surfactant Administration (LISA)

ACTIVE COMPARATOR

Infants that are spontaneously breathing with a normal heart rate will be randomized to receive prophylactic surfactant (Curosurf 2.5 mL/kg, based on estimated fetal weight) by the LISA procedure in the first 2 hours of life, using a conventional or video laryngoscope and a small flexible 16 gauge angiocatheter. Any repeat dosing for surfactant will be based on clinical indication at the physician discretion by the conventional endotracheal approach.

Procedure: Less Invasive Surfactant Administration LISA

Continuous Positive Airway Pressure (CPAP)

ACTIVE COMPARATOR

Infants that are spontaneously breathing with a normal heart rate will be randomized to early Continuous Positive Airway Pressure (CPAP).

Procedure: Continuous Positive Airway Pressure CPAP

Interventions

Less Invasive Surfactant Administration LISA PROCEDURE

Laryngoscopy with insertion of a small 16 gauge angiocatheter to administer FDA approved Surfactant, during spontaneous respirations.

Less Invasive Surfactant Administration (LISA)

Continuous Positive Airway Pressure CPAP PROCEDURE

Infant will remain on CPAP Therapy during spontaneous respirations

Continuous Positive Airway Pressure (CPAP)

Eligibility Criteria

• Age: 24 Weeks - 29 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Premature infants born at 24 to 29+6 weeks gestation
• Informed consent obtained (antenatal)
• Infant is spontaneously breathing on CPAP of 5-8 cmH2O and maintaining a normal heart rate (HR\>100 Bpm)

You may not qualify if:

• Declined consent
• Infants with known congenital anomalies
• Unstable immediately after birth, requiring intubation in the delivery room

Sponsors & Collaborators

• Sharp HealthCare: lead
• Sharp Mary Birch Hospital for Women & Newborns: collaborator
• Loma Linda University: collaborator
• University of California, Irvine: collaborator

Study Sites (3)

University of California, Irvine

Irvine, California, 92868, United States

Location

Loma Linda Medical Center

Loma Linda, California, 92350, United States

Location

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

Location

Related Publications (12)

• Gopel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, Siegel J, Avenarius S, von der Wense A, Vochem M, Groneck P, Weller U, Moller J, Hartel C, Haller S, Roth B, Herting E; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet. 2011 Nov 5;378(9803):1627-34. doi: 10.1016/S0140-6736(11)60986-0. Epub 2011 Sep 29.

  PMID: 21963186 BACKGROUND

• Kribs A, Hartel C, Kattner E, Vochem M, Kuster H, Moller J, Muller D, Segerer H, Wieg C, Gebauer C, Nikischin W, Wense Av, Herting E, Roth B, Gopel W. Surfactant without intubation in preterm infants with respiratory distress: first multi-center data. Klin Padiatr. 2010 Jan-Feb;222(1):13-7. doi: 10.1055/s-0029-1241867. Epub 2010 Jan 18.

  PMID: 20084586 BACKGROUND

• Isayama T, Iwami H, McDonald S, Beyene J. Association of Noninvasive Ventilation Strategies With Mortality and Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review and Meta-analysis. JAMA. 2016 Aug 9;316(6):611-24. doi: 10.1001/jama.2016.10708.

  PMID: 27532916 BACKGROUND

• Bhayat S, Kaur A, Premadeva I, Reynolds P, Gowda H. Survey of less Invasive Surfactant Administration in England, slow adoption and variable practice. Acta Paediatr. 2020 Mar;109(3):505-510. doi: 10.1111/apa.14995. Epub 2019 Sep 16.

  PMID: 31471992 BACKGROUND

• SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sanchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16.

  PMID: 20472939 BACKGROUND

• Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111(2):107-125. doi: 10.1159/000448985. Epub 2016 Sep 21.

  PMID: 27649091 BACKGROUND

• Katheria AC, Leone TA. Changes in hemodynamics after rescue surfactant administration. J Perinatol. 2013 Jul;33(7):525-8. doi: 10.1038/jp.2012.166. Epub 2013 Jan 17.

  PMID: 23328925 BACKGROUND

• Dekker J, Hooper SB, van Vonderen JJ, Witlox RSGM, Lopriore E, Te Pas AB. Caffeine to improve breathing effort of preterm infants at birth: a randomized controlled trial. Pediatr Res. 2017 Aug;82(2):290-296. doi: 10.1038/pr.2017.45. Epub 2017 May 17.

  PMID: 28288150 BACKGROUND

• 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 BACKGROUND

• Dorner RA, Morales A, Banerji A, Uy C, Ines F, Finer N, Vaucher Y, Katheria AC. Two-Year Outcomes of Less Invasive Surfactant Administration Among Preterm Neonates: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e263852. doi: 10.1001/jamanetworkopen.2026.3852.

  PMID: 41915392 DERIVED

• Katheria A, Ines F, Banerji A, Hopper A, Uy C, Chundu A, Coughlin K, Hutson S, Morales A, Sauberan J, Poeltler D, Dorner R, Rich W, Finer N. Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn. NEJM Evid. 2023 Dec;2(12):EVIDoa2300183. doi: 10.1056/EVIDoa2300183. Epub 2023 Nov 21.

  PMID: 38320499 DERIVED

• Ines F, Hutson S, Coughlin K, Hopper A, Banerji A, Uy C, Finer N, Rich W, Morales A, Steen J, Katheria AC. Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol. BMJ Open. 2021 Jan 22;11(1):e038343. doi: 10.1136/bmjopen-2020-038343.

  PMID: 33483435 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Pulmonary Atelectasis; Premature Birth

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Anup Katheria

  Sharp HealthCare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neonatal Research Institute

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: December 24, 2019
• Study Start: January 22, 2020
• Primary Completion: May 8, 2023
• Study Completion: November 10, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months and ending 36 months following article publication
• Access Criteria: Data and publication are available at http://clinicaltrials.gov

Locations

US (3)