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

Respiratory Distress Syndrome Clinical Trial

— CaLI  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04209946
• Other study ID #: CaLI
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 22, 2020
• Est. completion date: June 2025

Study information

• Verified date: August 2023
• Source: Sharp HealthCare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 180
• Est. completion date: June 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Weeks to 29 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Premature Lungs
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Surfactant Deficiency Syndrome Neonatal
• Syndrome

Intervention

Procedure:
• Less Invasive Surfactant Administration LISA
Laryngoscopy with insertion of a small 16 gauge angiocatheter to administer FDA approved Surfactant, during spontaneous respirations.
• Continuous Positive Airway Pressure CPAP
Infant will remain on CPAP Therapy during spontaneous respirations

Locations

Country	Name	City	State
United States	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

Sponsors (4)

Lead Sponsor	Collaborator
Sharp HealthCare	Loma Linda University, Sharp Mary Birch Hospital for Women & Newborns, University of California, Irvine

Country where clinical trial is conducted

United States, 

References & Publications (9)

Bhayat S, Kaur A, Premadeva I, Reynolds P, Gowda H. Survey of less Invasive Surfactant Administration in England, slow adoption and variable practice. Acta Paediatr. 2020 Mar;109(3):505-510. doi: 10.1111/apa.14995. Epub 2019 Sep 16. — View Citation

Dekker J, Hooper SB, van Vonderen JJ, Witlox RSGM, Lopriore E, Te Pas AB. Caffeine to improve breathing effort of preterm infants at birth: a randomized controlled trial. Pediatr Res. 2017 Aug;82(2):290-296. doi: 10.1038/pr.2017.45. Epub 2017 May 17. — View Citation

Gopel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, Siegel J, Avenarius S, von der Wense A, Vochem M, Groneck P, Weller U, Moller J, Hartel C, Haller S, Roth B, Herting E; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet. 2011 Nov 5;378(9803):1627-34. doi: 10.1016/S0140-6736(11)60986-0. Epub 2011 Sep 29. — View Citation

Isayama T, Iwami H, McDonald S, Beyene J. Association of Noninvasive Ventilation Strategies With Mortality and Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review and Meta-analysis. JAMA. 2016 Aug 9;316(6):611-24. doi: 10.1001/jama.2016.10708. Erratum In: JAMA. 2016 Sep 13;316(10):1116. — View Citation

Katheria AC, Leone TA. Changes in hemodynamics after rescue surfactant administration. J Perinatol. 2013 Jul;33(7):525-8. doi: 10.1038/jp.2012.166. Epub 2013 Jan 17. — View Citation

Kribs A, Hartel C, Kattner E, Vochem M, Kuster H, Moller J, Muller D, Segerer H, Wieg C, Gebauer C, Nikischin W, Wense Av, Herting E, Roth B, Gopel W. Surfactant without intubation in preterm infants with respiratory distress: first multi-center data. Klin Padiatr. 2010 Jan-Feb;222(1):13-7. doi: 10.1055/s-0029-1241867. Epub 2010 Jan 18. — View Citation

Kurepa D, Perveen S, Lipener Y, Kakkilaya V. The use of less invasive surfactant administration (LISA) in the United States with review of the literature. J Perinatol. 2019 Mar;39(3):426-432. doi: 10.1038/s41372-018-0302-9. Epub 2019 Jan 11. — View Citation

SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sanchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16. Erratum In: N Engl J Med. 2010 Jun 10;362(23):2235. — View Citation

Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111(2):107-125. doi: 10.1159/000448985. Epub 2016 Sep 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Laryngoscopy attempt with the LISA procedure	Total number of laryngoscopy attempts to administer surfactant via the LISA procedure	Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
Other	Laryngoscopy attempt with endotracheal intubation	Total number of laryngoscopy attempts to administer surfactant via endotracheal intubation	Number of laryngoscopy attempts per Surfactant dose, up to 36 weeks of corrected gestational age
Primary	Frequency of subjects requiring endotracheal intubation between the two groups (LISA vs CPAP) in the first 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	Within 72 hours of life
Secondary	Duration of mechanical ventilation and/or CPAP	Number of days on mechanical ventilation and/or CPAP	Through study completion at discharge, up to 6 months of corrected gestational age
Secondary	Oxygen at 36 weeks corrected age	Requiring oxygen therapy greater than 0.21 at 36 weeks corrected age	Up to 40 weeks of corrected gestational age
Secondary	Frequency of Grade III and IV intraventricular hemorrhage	Intraventricular hemorrhage (grades 3-4)	Through study completion at discharge, up to 6 months of corrected gestational age
Secondary	Neurodevelopment outcome at 24 months 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.	Up to 2 years of corrected gestational age
Secondary	Neurodevelopment outcome at 2 Years of Age	Overall and Domain Scores- Ages and Stages, 3rd ed. Questionnaire	22-26 months corrected gestational age
Secondary	Need for repeat surfactant dosing	Requiring more than one dose of surfactant	Up to 40 weeks of corrected gestational age