Premedication for Less Invasive Surfactant Administration Study (PRELISA)

NCT ID: NCT05065424

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE4

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-06

Study Completion Date

2026-07-01

Brief Summary

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The purpose of this study is to conduct a double blinded randomized control trial to determine the safety and efficacy of using IV fentanyl and atropine prior to Less Invasive Surfactant Administration (LISA) procedure in preterm infants with Respiratory Distress Syndrome compared to the local standard of care to perform this procedure without any premedication.

Hypothesis: In infants greater than or equal to 29 weeks gestational age requiring the Less Invasive Surfactant Administration procedure, premedication with a combination of IV atropine and IV fentanyl will be associated with fewer combined bradycardia events, defined as heartrate less than 100 beats per minute for longer than 10 seconds, and hypoxemia events, defined as saturations less than or equal to 80% for longer than 30 seconds, during the procedure compared with placebo.

Specific Aims:

* To determine if infants ≥29 week GA receiving IV fentanyl and atropine prior to LISA will have a decrease in hypoxemia and bradycardia events during the procedure compared to infants receiving placebo
* To determine if infants ≥29 week GA receiving premedication prior to Less Invasive Surfactant Administration will have higher procedure first attempt success rate compared with infants receiving placebo
* To determine the effect of premedication on cerebral oxygenation compared to placebo during and for 12 hours after Less Invasive Surfactant Administration in infants ≥29 week GA using cerebral Near Infrared Spectroscopy.
* To determine the effect of premedication prior to Less Invasive Surfactant Administration on the need for mechanical ventilation during ≤72 hours of life in preterm infants.

Detailed Description

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Conditions

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Respiratory Distress Syndrome, Newborn

Keywords

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Premedication for Less Invasive Surfactant Administration Fentanyl and Atropine for Less Invasive Surfactant Administration Cerebral Near Infrared Spectroscopy monitoring in neonates Premedication for LISA Fentanyl and Atropine for LISA Cerebral NIRS monitoring in neonates

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Quadruple Blinded
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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IV Atropine and Fentanyl Premedication Arm

Participants will receive premedication regimen of 20 micrograms/kilogram intravenous atropine and 0.5 micrograms/kilogram intravenous fentanyl prior to performance of LISA.

Group Type EXPERIMENTAL

IV Atropine and Fentanyl Premedication Arm

Intervention Type DRUG

Prior to the LISA procedure, the blinded bedside nurse will infuse IV Atropine, labelled as "Atropine/Placebo," over 1 minute, followed by IV fentanyl, labelled as "Fentanyl/Placebo," over 20 minutes in the presence of blinded respiratory therapist and primary team provider.

After medication infusion, a primary team member will perform Less Invasive Surfactant Administration procedure. Infant vital signs, cerebral Near Infrared Spectroscopy values, pain scores will be monitored and recorded during and for 12 hours after the procedure. Level of respiratory support, oxygen requirement and subsequent need for intubation for 24 hours after the procedure will be obtained from the electronic medical record.

IV Normal Saline Placebo Arm

Participants will receive two intravenous Normal Saline infusions in quantities equivalent to the calculated volumes of atropine and fentanyl for participant's weight prior to performance of LISA.

Group Type PLACEBO_COMPARATOR

IV Normal Saline Placebo Arm

Intervention Type DRUG

Prior to the Less Invasive Surfactant Administration procedure, the blinded bedside nurse will infuse IV Normal Saline, labelled as "Atropine/Placebo," over 1 minute, followed by a second infusion of IV Normal Saline, labelled as "Fentanyl/Placebo," over 20 minutes in the presence of blinded respiratory therapist and primary team provider.

After Normal Saline infusion, primary team member will perform Less Invasive Surfactant Administration procedure. Infant vital signs, cerebral Near Infrared Spectroscopy values, pain scores will be monitored and recorded during and for 12 hours after the procedure. Level of respiratory support, oxygen requirement and subsequent need for intubation for 24 hours after the procedure will be obtained from the electronic medical record.

Interventions

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IV Atropine and Fentanyl Premedication Arm

Prior to the LISA procedure, the blinded bedside nurse will infuse IV Atropine, labelled as "Atropine/Placebo," over 1 minute, followed by IV fentanyl, labelled as "Fentanyl/Placebo," over 20 minutes in the presence of blinded respiratory therapist and primary team provider.

After medication infusion, a primary team member will perform Less Invasive Surfactant Administration procedure. Infant vital signs, cerebral Near Infrared Spectroscopy values, pain scores will be monitored and recorded during and for 12 hours after the procedure. Level of respiratory support, oxygen requirement and subsequent need for intubation for 24 hours after the procedure will be obtained from the electronic medical record.

Intervention Type DRUG

IV Normal Saline Placebo Arm

Prior to the Less Invasive Surfactant Administration procedure, the blinded bedside nurse will infuse IV Normal Saline, labelled as "Atropine/Placebo," over 1 minute, followed by a second infusion of IV Normal Saline, labelled as "Fentanyl/Placebo," over 20 minutes in the presence of blinded respiratory therapist and primary team provider.

After Normal Saline infusion, primary team member will perform Less Invasive Surfactant Administration procedure. Infant vital signs, cerebral Near Infrared Spectroscopy values, pain scores will be monitored and recorded during and for 12 hours after the procedure. Level of respiratory support, oxygen requirement and subsequent need for intubation for 24 hours after the procedure will be obtained from the electronic medical record.

Intervention Type DRUG

Other Intervention Names

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IV Atropine sulfate and IV Fentanyl citrate

Eligibility Criteria

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Inclusion Criteria

* Infants ≥29 weeks gestational age initiated on CPAP in the delivery room or upon admission who require ≥0.25 FiO2.

Exclusion Criteria

* Infants requiring intubation prior to surfactant therapy
* Infants with known severe congenital anomalies (including complex congenital heart disease, airway, and central nervous system anomalies)
* Infants born to mothers with known opioid addiction or in a methadone treatment program
* Maternal COVID19 infection (RT-PCR positive) within two weeks prior to delivery
Minimum Eligible Age

0 Hours

Maximum Eligible Age

72 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Venkat Kakkilaya

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Venkatakrishna Kakkilaya, MD

Role: STUDY_DIRECTOR

University of Texas Southwestern Medical Center

Locations

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Parkland Health and Hospital System

Dallas, Texas, United States

Site Status

Countries

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United States

References

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Reference Type BACKGROUND
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Anand KJ; International Evidence-Based Group for Neonatal Pain. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med. 2001 Feb;155(2):173-80. doi: 10.1001/archpedi.155.2.173.

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Boggini T, Pozzoli S, Schiavolin P, Erario R, Mosca F, Brambilla P, Fumagalli M. Cumulative procedural pain and brain development in very preterm infants: A systematic review of clinical and preclinical studies. Neurosci Biobehav Rev. 2021 Apr;123:320-336. doi: 10.1016/j.neubiorev.2020.12.016. Epub 2020 Dec 20.

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Bourgoin L, Caeymaex L, Decobert F, Jung C, Danan C, Durrmeyer X. Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates. Acta Paediatr. 2018 Jul;107(7):1184-1190. doi: 10.1111/apa.14317. Epub 2018 Apr 16.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 22374882 (View on PubMed)

Committee on Fetus and Newborn; American Academy of Pediatrics. Respiratory support in preterm infants at birth. Pediatrics. 2014 Jan;133(1):171-4. doi: 10.1542/peds.2013-3442. Epub 2013 Dec 30.

Reference Type BACKGROUND
PMID: 24379228 (View on PubMed)

Chevallier M, Durrmeyer X, Ego A, Debillon T; PROLISA Study Group. Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA). BMC Pediatr. 2020 May 8;20(1):199. doi: 10.1186/s12887-020-02112-x.

Reference Type BACKGROUND
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Dekker J, Lopriore E, van Zanten HA, Tan RNGB, Hooper SB, Te Pas AB. Sedation during minimal invasive surfactant therapy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F378-F383. doi: 10.1136/archdischild-2018-315015. Epub 2018 Aug 1.

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Descamps CS, Chevallier M, Ego A, Pin I, Epiard C, Debillon T. Propofol for sedation during less invasive surfactant administration in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2017 Sep;102(5):F465. doi: 10.1136/archdischild-2017-312791. Epub 2017 May 8. No abstract available.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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Other Identifiers

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STU-2021-0380

Identifier Type: -

Identifier Source: org_study_id