Clinical trial NCT04209946: Early Caffeine and LISA Compared to Caffeine and CPAP in Preterm Infants
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
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)
Lead sponsor: Sharp HealthCare
Sponsor class: OTHER
Collaborators: name: Sharp Mary Birch Hospital for Women & Newborns
name: Loma Linda University
name: University of California, Irvine
First posted: 2019-12-24
Enrollment: 180
Sex: ALL
Minimum age (years): 24
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of subjects requiring endotracheal intubation between the two groups (LISA vs CPAP) in the first 72 hours of life
timeFrame: Within 72 hours of life
Secondary outcomes:
measure: Duration of mechanical ventilation and/or CPAP
timeFrame: Through study completion at discharge, up to 6 months of corrected gestational age
measure: Oxygen at 36 weeks corrected age
timeFrame: Up to 40 weeks of corrected gestational age
measure: Frequency of Grade III and IV intraventricular hemorrhage
timeFrame: Through study completion at discharge, up to 6 months of corrected gestational age
measure: Neurodevelopment outcome at 24 months of corrected gestational age
timeFrame: Up to 2 years of corrected gestational age
measure: Neurodevelopment outcome at 2 Years of Age
timeFrame: 22-26 months corrected gestational age
measure: Need for repeat surfactant dosing
timeFrame: Up to 40 weeks of corrected gestational age
Other outcomes:
measure: Laryngoscopy attempt with the LISA procedure
timeFrame: Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
measure: Laryngoscopy attempt with endotracheal intubation
timeFrame: Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Loma Linda
country: United States
facility: Loma Linda Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women & Newborns
state: California
Study officials:
affiliation: Sharp HealthCare
name: Anup Katheria
role: PRINCIPAL_INVESTIGATOR
References:
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