Premature LungsCaLINCT04209946
Early Caffeine and LISA Compared to Caffeine and CPAP in Preterm Infants
A study testing Less Invasive Surfactant Administration LISA and Continuous Positive Airway Pressure CPAP in people with Premature Lungs and Respiratory Distress Syndrome, run by Sharp HealthCare at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 24 to 29 weeks
- Conditions the study is for
- Premature Lungs, Respiratory Distress Syndrome, Surfactant Deficiency Syndrome Neonatal
- What is being tested?
- Less Invasive Surfactant Administration LISA and Continuous Positive Airway Pressure CPAP
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 Jan 2020to 10 Nov 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 29 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- Declined consent
- Infants with known congenital anomalies
- Unstable immediately after birth, requiring intubation in the delivery room
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of California, Irvine
Irvine, California, 92868
Loma Linda Medical Center
Loma Linda, California, 92350
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
About this study
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)
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.
Read the 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).
- Being tested
- Less Invasive Surfactant Administration LISA, Continuous Positive Airway Pressure CPAP
- Keywords
- Premature Infants, Respiratory Distress Syndrome, Less Invasive Surfactant administration, Continuous Positive Airway Pressure (CPAP)
- Medical subject headings
- Respiratory Distress Syndrome, Pulmonary Atelectasis, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Less Invasive Surfactant Administration LISAProcedure or surgery
Laryngoscopy with insertion of a small 16 gauge angiocatheter to administer FDA approved Surfactant, during spontaneous respirations.
Continuous Positive Airway Pressure CPAPProcedure or surgery
Infant will remain on CPAP Therapy during spontaneous respirations
| Study group | Role | What they receive |
|---|---|---|
| Less Invasive Surfactant Administration (LISA) | Active comparator | 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. Receives: Procedure: Less Invasive Surfactant Administration LISA |
| Continuous Positive Airway Pressure (CPAP) | Active comparator | Infants that are spontaneously breathing with a normal heart rate will be randomized to early Continuous Positive Airway Pressure (CPAP). Receives: Procedure: Continuous Positive Airway Pressure CPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 72 hours of life
Secondary outcomes (6)
Duration of mechanical ventilation and/or CPAP
Number of days on mechanical ventilation and/or CPAP
Measured: Through study completion at discharge, up to 6 months of corrected gestational age
Oxygen at 36 weeks corrected age
Requiring oxygen therapy greater than 0.21 at 36 weeks corrected age
Measured: Up to 40 weeks of corrected gestational age
Frequency of Grade III and IV intraventricular hemorrhage
Intraventricular hemorrhage (grades 3-4)
Measured: Through study completion at discharge, up to 6 months of corrected gestational age
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.
Measured: Up to 2 years of corrected gestational age
Neurodevelopment outcome at 2 Years of Age
Overall and Domain Scores- Ages and Stages, 3rd ed. Questionnaire
Measured: 22-26 months corrected gestational age
Need for repeat surfactant dosing
Requiring more than one dose of surfactant
Measured: Up to 40 weeks of corrected gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start22 Jan 2020
- Primary completion8 May 2023
- Study completion10 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Premature LungsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sharp HealthCare
- Sponsor type
- University, hospital or other
- Collaborators
- Sharp Mary Birch Hospital for Women & Newborns, Loma Linda University, University of California, Irvine
- Responsible party
- Principal investigator, Anup Katheria, M.D., Sharp HealthCare
- Investigators
- Anup Katheria, Principal investigator, Sharp HealthCare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04209946
- Sponsor's protocol ID
- CaLI
- Acronym
- CaLI
- Status last verified
- Mar 2025
- First submitted
- 13 Dec 2019
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data, particularly data that underlie the results reported in this article after deidentification will be available with other researchers, including data dictionaries for meta-analysis.
Publications
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.
PubMed 21963186Kribs 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.
PubMed 20084586Isayama 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.
PubMed 27532916Bhayat 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.
PubMed 31471992SUPPORT 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.
PubMed 20472939Sweet 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.
PubMed 27649091Katheria 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.
PubMed 23328925Dekker 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.
PubMed 28288150Kurepa 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.
PubMed 30635595Dorner RA, Morales A, Banerji A, Uy C, Ines F, Finer N, Vaucher Y, Katheria AC. Two-Year Outcomes of Less Invasive Surfactant Administration Among Preterm Neonates: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e263852. doi: 10.1001/jamanetworkopen.2026.3852.
PubMed 41915392Katheria A, Ines F, Banerji A, Hopper A, Uy C, Chundu A, Coughlin K, Hutson S, Morales A, Sauberan J, Poeltler D, Dorner R, Rich W, Finer N. Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn. NEJM Evid. 2023 Dec;2(12):EVIDoa2300183. doi: 10.1056/EVIDoa2300183. Epub 2023 Nov 21.
PubMed 38320499Ines F, Hutson S, Coughlin K, Hopper A, Banerji A, Uy C, Finer N, Rich W, Morales A, Steen J, Katheria AC. Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol. BMJ Open. 2021 Jan 22;11(1):e038343. doi: 10.1136/bmjopen-2020-038343.
PubMed 33483435
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04209946
- Acronym / sponsor ID
- CaLI / CaLI
- Keywords
- Premature Infants, Respiratory Distress Syndrome, Less Invasive Surfactant administration, Continuous Positive Airway Pressure (CPAP)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Sharp HealthCareUniversity, hospital or other
- Collaborators
- Sharp Mary Birch Hospital for Women & Newborns, Loma Linda University, University of California, Irvine
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 8 May 2023 (actual)
- Study completion
- 10 Nov 2025 (actual)
- First posted
- 24 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Less Invasive Surfactant Administration (LISA) | Active comparator | Procedure: Less Invasive Surfactant Administration LISAInfants 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) | Active comparator | Procedure: Continuous Positive Airway Pressure CPAPInfants that are spontaneously breathing with a normal heart rate will be randomized to early Continuous Positive Airway Pressure (CPAP). |
Who may qualify
- Ages
- 24 to 29 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (3 listed)
- Declined consent
- Infants with known congenital anomalies
- Unstable immediately after birth, requiring intubation in the delivery room
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Less Invasive Surfactant Administration LISALaryngoscopy with insertion of a small 16 gauge angiocatheter to administer FDA approved Surfactant, during spontaneous respirations. | Procedure or surgery | Less Invasive Surfactant Administration (LISA) |
| Continuous Positive Airway Pressure CPAPInfant will remain on CPAP Therapy during spontaneous respirations | Procedure or surgery | Continuous Positive Airway Pressure (CPAP) |
Primary outcome
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
6 secondary outcomes
Duration of mechanical ventilation and/or CPAP
Time frame: Through study completion at discharge, up to 6 months of corrected gestational age
Oxygen at 36 weeks corrected age
Time frame: Up to 40 weeks of corrected gestational age
Frequency of Grade III and IV intraventricular hemorrhage
Time frame: Through study completion at discharge, up to 6 months of corrected gestational age
Neurodevelopment outcome at 24 months of corrected gestational age
Time frame: Up to 2 years of corrected gestational age
Neurodevelopment outcome at 2 Years of Age
Time frame: 22-26 months corrected gestational age
Need for repeat surfactant dosing
Time frame: Up to 40 weeks of corrected gestational age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Background: PubMed 21963186Gopel 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.
- Background: PubMed 20084586Kribs 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.
- Background: PubMed 27532916Isayama 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.
- Background: PubMed 31471992Bhayat 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.
- Background: PubMed 20472939SUPPORT 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.
- Background: PubMed 27649091Sweet 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.
- Background: PubMed 23328925Katheria 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.
- Background: PubMed 28288150Dekker 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.
- Background: PubMed 30635595Kurepa 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.
- Derived from this study: PubMed 41915392Dorner RA, Morales A, Banerji A, Uy C, Ines F, Finer N, Vaucher Y, Katheria AC. Two-Year Outcomes of Less Invasive Surfactant Administration Among Preterm Neonates: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e263852. doi: 10.1001/jamanetworkopen.2026.3852.
- Derived from this study: PubMed 38320499Katheria A, Ines F, Banerji A, Hopper A, Uy C, Chundu A, Coughlin K, Hutson S, Morales A, Sauberan J, Poeltler D, Dorner R, Rich W, Finer N. Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn. NEJM Evid. 2023 Dec;2(12):EVIDoa2300183. doi: 10.1056/EVIDoa2300183. Epub 2023 Nov 21.
- Derived from this study: PubMed 33483435Ines F, Hutson S, Coughlin K, Hopper A, Banerji A, Uy C, Finer N, Rich W, Morales A, Steen J, Katheria AC. Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol. BMJ Open. 2021 Jan 22;11(1):e038343. doi: 10.1136/bmjopen-2020-038343.
- Individual participant dataSharing planned: Yes. Individual participant data, particularly data that underlie the results reported in this article after deidentification will be available with other researchers, including data dictionaries for meta-analysis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anup Katheria principal investigator
Sharp HealthCare
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Less Invasive Surfactant Administration LISA and Continuous Positive Airway Pressure CPAP in people with Premature Lungs and Respiratory Distress Syndrome, run by Sharp HealthCare at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04209946, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025; AzTrials last refreshed its copy on 6 Nov 2026.