Early Caffeine and LISA Compared to Caffeine and CPAP in Preterm Infants (CaLI)

August 29, 2023 updated by: Anup Katheria, M.D., Sharp HealthCare

A Multicenter, Randomized Trial of Preterm Infants Receiving Caffeine and Less Invasive Surfactant Administration Compared to Caffeine and Early Continuous Positive Airway Pressure (CaLI Trial)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

In order to allow for initial stabilization on CPAP, infants will be randomized by 1 hour of life. Consented infants that are assessed by a provider as clinically stable (i.e. HR> 100 bpm) and spontaneously breathing on CPAP will be randomized by computer generated randomization cards placed in opaque envelopes.

Randomization will be stratified by gestational age (24-26+6 weeks and 27-29+6 weeks) and labeled as such on each envelope. Multiples will be randomized to the same treatment group for ease of consent and family considerations.

Infants randomized to LISA will receive surfactant (Curosurf 2.5 mL/kg, based on estimated fetal weight) and must be given in the first 2 hours of life using a conventional or video laryngoscope and a small flexible 16 gauge angiocatheter.

All sites have agreed on using senior level physicians or practitioners that have prior experience with the LISA method. An orogastric tube will be placed into the stomach prior to laryngoscopy and the contents aspirated after the procedure to document any esophageal surfactant administration.

Infants randomized to early CPAP will be managed according to unit practice for preterm infants on CPAP.

Caffeine Administration:

If randomized to LISA, caffeine will be given prior to the LISA procedure. In contrast, if randomized to CPAP, caffeine will be given soon after birth. If infants in the CPAP group meet intubation criteria, and the loading dose of caffeine has not been administered, to avoid delay in intubation, caffeine will be given no later than thirty minutes after intubation.

As an unblinded trial it is critical that both groups are standardized to avoid bias towards one arm for intubation/treatment failure. Therefore, strict delivery room/NICU criteria will be used.

In the Delivery Room, criteria for intubation will be as specified in the Neonatal Resuscitation Program guidelines (7th Ed) and will include:

  1. Chest compressions
  2. Ineffective respiration
  3. Prolonged positive pressure ventilation (PPV)
  4. Prolonged hypoxia

In the Neonatal Intensive Care Unit (NICU), randomized infants in both groups will only be intubated if they meet strict failure criteria :

  1. CPAP level of 6-8 cmH2O and FiO2> 0.40 required to maintain oxygen saturation >90% for 2 hours after randomization
  2. pH of 7.15 or less OR a partial pCO2 >65 mmHg on any (2) blood gas (arterial/capillary/ or venous) at least 2 hours after randomization in the first 72 hours of life.
  3. Continued Apnea/Bradycardia/Desaturation events despite nasal intermittent minute ventilation (NIMV) mode of ventilation.

Infants intubated prior to randomization will be excluded. Infants not consented prior to birth will also be excluded to avoid bias in patient selection.

For pragmatic purposes sites will be able to use their standard approach for non-invasive ventilation (NCPAP or NIMV).

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Irvine, California, United States, 92868
        • University of California, Irvine
      • Loma Linda, California, United States, 92350
        • Loma Linda Medical Center
      • San Diego, California, United States, 92123
        • Sharp Mary Birch Hospital for Women & Newborns

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 6 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Less Invasive Surfactant Administration (LISA)
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
Laryngoscopy with insertion of a small 16 gauge angiocatheter to administer FDA approved Surfactant, during spontaneous respirations.
Active Comparator: Continuous Positive Airway Pressure (CPAP)
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
Infant will remain on CPAP Therapy during spontaneous respirations

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of subjects requiring endotracheal intubation between the two groups (LISA vs CPAP) in the first 72 hours of life
Time Frame: Within 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of mechanical ventilation and/or CPAP
Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
Number of days on mechanical ventilation and/or CPAP
Through study completion at discharge, up to 6 months of corrected gestational age
Oxygen at 36 weeks corrected age
Time Frame: Up to 40 weeks of corrected gestational age
Requiring oxygen therapy greater than 0.21 at 36 weeks corrected age
Up to 40 weeks of corrected gestational age
Frequency of Grade III and IV intraventricular hemorrhage
Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
Intraventricular hemorrhage (grades 3-4)
Through study completion at discharge, up to 6 months of corrected gestational age
Neurodevelopment outcome at 24 months of corrected gestational age
Time Frame: Up to 2 years of corrected gestational age
Neurodevelopmental assessments using the Bayley Scales of Infant Development 4th ed. will be done at 2 years of corrected corrected age (22-26 months) for subjects who were randomized at birth to receive surfactant by the LISA method versus CPAP alone.
Up to 2 years of corrected gestational age
Neurodevelopment outcome at 2 Years of Age
Time Frame: 22-26 months corrected gestational age
Overall and Domain Scores- Ages and Stages, 3rd ed. Questionnaire
22-26 months corrected gestational age
Need for repeat surfactant dosing
Time Frame: Up to 40 weeks of corrected gestational age
Requiring more than one dose of surfactant
Up to 40 weeks of corrected gestational age

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Laryngoscopy attempt with the LISA procedure
Time Frame: Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
Total number of laryngoscopy attempts to administer surfactant via the LISA procedure
Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
Laryngoscopy attempt with endotracheal intubation
Time Frame: Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
Total number of laryngoscopy attempts to administer surfactant via endotracheal intubation
Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sharp HealthCare

Collaborators

University of California, Irvine
Loma Linda University
Sharp Mary Birch Hospital for Women & Newborns

Investigators

  • Principal Investigator: Anup Katheria, Sharp HealthCare

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2020

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

December 13, 2019

First Submitted That Met QC Criteria

December 23, 2019

First Posted (Actual)

December 24, 2019

Study Record Updates

Last Update Posted (Estimated)

August 31, 2023

Last Update Submitted That Met QC Criteria

August 29, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CaLI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data, particularly data that underlie the results reported in this article after deidentification will be available with other researchers, including data dictionaries for meta-analysis.

IPD Sharing Time Frame

Beginning 6 months and ending 36 months following article publication

IPD Sharing Access Criteria

Data and publication are available at http://clinicaltrials.gov

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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