Early Caffeine and LISA Compared to Caffeine and CPAP in Preterm Infants (CaLI)
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|ClinicalTrials.gov Identifier: NCT04209946|
Recruitment Status : Recruiting
First Posted : December 24, 2019
Last Update Posted : January 22, 2021
|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||Not Applicable|
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.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 :||January 22, 2020|
|Estimated Primary Completion Date :||January 2025|
|Estimated Study Completion Date :||June 2025|
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
- 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
- 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
- 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
- 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)
- 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.
- Need for repeat surfactant dosing [ Time Frame: Up to 40 weeks of corrected gestational age ]Requiring more than one dose of surfactant
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209946
|Contact: Anup Katheriaemail@example.com|
|Contact: Felix Inesfirstname.lastname@example.org|
|United States, California|
|University of California, Irvine||Not yet recruiting|
|Irvine, California, United States, 92868|
|Contact: Cherry Uy, MD 714-456-6933 email@example.com|
|Contact: Anupama Chundu, MD 714-456-6933 firstname.lastname@example.org|
|Loma Linda Medical Center||Not yet recruiting|
|Loma Linda, California, United States, 92350|
|Contact: Andrew Hopper, MD AHopper@llu.edu|
|Contact: Anamika Banerji, MD ABanerji@llu.edu|
|Sharp Mary Birch Hospital for Women & Newborns||Recruiting|
|San Diego, California, United States, 92123|
|Contact: Anup Katheria, MD 858-939-4170 email@example.com|
|Contact: Felix Ines, RCP-RRT 858-939-4136 firstname.lastname@example.org|
|Sub-Investigator: Shandee Hutson, MD|
|Principal Investigator:||Anup Katheria||Sharp HealthCare|