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

Sponsor

Sharp HealthCare (Other)

Overall Status

Recruiting

CT.gov ID

NCT04209946

Collaborator

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

180

Enrollment

Locations

Arms

64.3

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Premature Lungs Respiratory Distress Syndrome Surfactant Deficiency Syndrome Neonatal	Procedure: Less Invasive Surfactant Administration LISA Procedure: Continuous Positive Airway Pressure CPAP	N/A

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:

Chest compressions
Ineffective respiration
Prolonged positive pressure ventilation (PPV)
Prolonged hypoxia

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

CPAP level of 6-8 cmH2O and FiO2> 0.40 required to maintain oxygen saturation >90% for 2 hours after randomization
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.
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 Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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)

Actual Study Start Date :

Jan 22, 2020

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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
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 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.
Need for repeat surfactant dosing [Up to 40 weeks of corrected gestational age]
Requiring more than one dose of surfactant

Other Outcome Measures

Laryngoscopy attempt with the LISA procedure [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
Laryngoscopy attempt with endotracheal intubation [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

24 Weeks to 29 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Irvine	Irvine	California	United States	92868
2	Loma Linda Medical Center	Loma Linda	California	United States	92350
3	Sharp Mary Birch Hospital for Women & Newborns	San Diego	California	United States	92123