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

Not Applicable

Active, not recruiting

• Conditions: Premature Lungs; Surfactant Deficiency Syndrome Neonatal; Respiratory Distress Syndrome
• Interventions: Procedure: Less Invasive Surfactant Administration LISA; Procedure: Continuous Positive Airway Pressure CPAP

• Registration Number: NCT04209946
• Lead Sponsor: Sharp HealthCare

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.

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 Timeline

• Study First Submitted: 2019-12-13
• Study First Submitted QC: 2019-12-23
• Study First Posted: 2019-12-24
• Study Start: 2020-01-22
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-29
• Last Update Posted: 2023-08-31
• Primary Completion: 2025-01
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 180

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)

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Less Invasive Surfactant Administration (LISA)	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.
Continuous Positive Airway Pressure (CPAP)	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Oxygen at 36 weeks corrected age	Up to 40 weeks of corrected gestational age	Requiring oxygen therapy greater than 0.21 at 36 weeks corrected age
Frequency of Grade III and IV intraventricular hemorrhage	Through study completion at discharge, up to 6 months of corrected gestational age	Intraventricular hemorrhage (grades 3-4)
Neurodevelopment outcome at 2 Years of Age	22-26 months corrected gestational age	Overall and Domain Scores- Ages and Stages, 3rd ed. Questionnaire
Need for repeat surfactant dosing	Up to 40 weeks of corrected gestational age	Requiring more than one dose of surfactant
Duration of mechanical ventilation and/or CPAP	Through study completion at discharge, up to 6 months of corrected gestational age	Number of days on mechanical ventilation and/or CPAP
Neurodevelopment outcome at 24 months of corrected gestational age	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.

Trial Locations

Locations (3)

University of California, Irvine; 🇺🇸 Irvine, California, United States

Loma Linda Medical Center; 🇺🇸 Loma Linda, California, United States

Sharp Mary Birch Hospital for Women & Newborns; 🇺🇸 San Diego, California, United States