Early Caffeine + LISA vs. CPAP for Neonatal Respiratory Distress Syndrome

(CaLI Trial)

Recruiting at 2 trial locations

Overseen By Felix Ines

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Sharp HealthCare

Disqualifiers: Congenital anomalies, Unstable birth, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 23

Duration: 72 hours

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if giving a special liquid called surfactant to preterm babies using a gentle method can reduce the need for a breathing machine. The study focuses on babies born very early who are already getting some breathing support. The surfactant helps keep their lungs open, making it easier to breathe. Surfactant therapy has been a major contribution to the care of preterm newborns over the years.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the treatment Early Caffeine + LISA vs. CPAP for Neonatal Respiratory Distress Syndrome?

Research shows that using CPAP (a breathing support method) right after birth can reduce the risk of lung problems and death in premature babies. Combining CPAP with LISA (a gentle way to give lung medicine) and early caffeine (a drug that helps with breathing) may further reduce the need for more invasive breathing support. ^{1 2 3 4 5}

Is the combination of early caffeine, LISA, and CPAP safe for treating neonatal respiratory distress syndrome?

The combination of early caffeine, less invasive surfactant administration (LISA), and continuous positive airway pressure (CPAP) is generally considered safe for preterm infants with respiratory distress syndrome. Studies show that LISA reduces the need for mechanical ventilation and improves outcomes without significant differences in overall mortality or other serious complications. ^{1 2 4 6 7}

How does the treatment of early caffeine and LISA with CPAP differ from other treatments for neonatal respiratory distress syndrome?

This treatment is unique because it combines early caffeine therapy with less invasive surfactant administration (LISA) and continuous positive airway pressure (CPAP) to reduce the need for mechanical ventilation in premature infants. LISA uses a thin catheter to deliver surfactant, avoiding the need for intubation, which is less common in the U.S. but has shown improved outcomes in other countries. ^{1 2 3 4 5}

Research Team

Anup Katheria

Principal Investigator

Sharp HealthCare

Eligibility Criteria

This trial is for premature infants born between 24 and just under 30 weeks of gestation. They must be breathing on their own with CPAP support and have a normal heart rate. Infants can't join if they have birth defects, didn't get parental consent, or needed intubation right after birth due to instability.

Inclusion Criteria

My infant breathes on their own with CPAP support and has a normal heart rate.

My baby was born prematurely between 24 and just under 30 weeks.

Informed consent obtained (antenatal)

Exclusion Criteria

Babies with known birth defects.

I needed a breathing tube right after birth.

Declined consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 hour

1 visit (in-person)

Treatment

Infants receive either LISA or CPAP treatment within the first 2 hours of life

72 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months of corrected gestational age

Regular assessments until discharge

Long-term follow-up

Neurodevelopmental assessments using the Bayley Scales of Infant Development at 2 years of corrected age

Up to 2 years of corrected gestational age

Assessments at 22-26 months

Treatment Details

Interventions

• Continuous Positive Airway Pressure CPAP
• Less Invasive Surfactant Administration LISA

Trial Overview The study compares two treatments for preterm lung problems: one group receives surfactant through the Less Invasive Surfactant Administration (LISA) method, while the other gets early Continuous Positive Airway Pressure (CPAP) alone to see which reduces mechanical ventilation need within the first 72 hours of life.

Participant Groups

Group I: Less Invasive Surfactant Administration (LISA) Active Control 1 Intervention

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.

Group II: Continuous Positive Airway Pressure (CPAP) Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Sharp HealthCare

Lead Sponsor

Trials

42

Recruited

17,600+

Sharp Mary Birch Hospital for Women & Newborns

Collaborator

Trials

13

Recruited

6,600+

University of California, Irvine

Collaborator

Trials

580

Recruited

4,943,000+

Loma Linda University

Collaborator

Trials

322

Recruited

267,000+

References

1. England pubmed.ncbi.nlm.nih.gov

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. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Ancillary therapies to enhance success of non-invasive modes of respiratory support - Approaches to delivery room use of surfactant and caffeine? [2018]

3. England pubmed.ncbi.nlm.nih.gov

Caffeine to prevent intermittent hypoxaemia in late preterm infants: randomised controlled dosage trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Should less invasive surfactant administration (LISA) become routine practice in US neonatal units? [2023]

5. Iran pubmed.ncbi.nlm.nih.gov

The efficacy and safety of two different doses of caffeine in respiratory function of preterm infants. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Short-Term Outcome after Repeated Less Invasive Surfactant Administration: A Retrospective Cohort Study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Less Invasive Surfactant Administration Reduces the Need for Mechanical Ventilation in Preterm Infants: A Meta-Analysis. [2022]