Premedication for Less Invasive Surfactant Administration Study (PRELISA)

NCT05065424 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: STU-2021-0380
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Respiratory Distress Syndrome, Newborn

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of bradycardia and hypoxemia events during LISA procedure

  * Bradycardia events will be defined as heartrate \<100 beats per minute for \>10 seconds. Heartrate will be obtained from the participant's heartrate monitor. * Hypoxemia events will be defined as participant saturation (SpO2) =\<80% for \>30 seconds. SpO2 will be obtained from the participant's pulse oximeter monitor. * Events will be recorded by the respiratory therapist and/ or bedside nurse present during the procedure

  Time of medication infusion to completion of LISA procedure

Secondary Outcomes (5)

• Percent of time spent with cerebral Near Infrared Spectroscopy (NIRS) values <55%

  From time of start of LISA procedure to 12 hours after procedure

• Procedure first attempt success rate

  At time of LISA procedure

• Intubation rate

  Within 24 hours after LISA procedure

• Mean number of attempts required

  At time of LISA procedure

• Mean duration of bradycardia and hypoxemia events

  Time of medication infusion to completion of LISA procedure

Study Arms (2)

IV Atropine and Fentanyl Premedication Arm

EXPERIMENTAL

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

Drug: IV Atropine and Fentanyl Premedication Arm

IV Normal Saline Placebo Arm

PLACEBO COMPARATOR

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.

Drug: IV Normal Saline Placebo Arm

Interventions

IV Atropine and Fentanyl Premedication Arm 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.

Also known as: IV Atropine sulfate and IV Fentanyl citrate

IV Atropine and Fentanyl Premedication Arm

IV Normal Saline Placebo Arm 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.

IV Normal Saline Placebo Arm

Eligibility Criteria

• Age: 0 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (1)

Parkland Health and Hospital System

Dallas, Texas, 75390, United States

Location

Related Publications (21)

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  PMID: 33359095 BACKGROUND

• 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.

  PMID: 29532502 BACKGROUND

• Brummelte S, Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, Gover A, Synnes AR, Miller SP. Procedural pain and brain development in premature newborns. Ann Neurol. 2012 Mar;71(3):385-96. doi: 10.1002/ana.22267. Epub 2012 Feb 28.

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• 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.

  PMID: 24379228 BACKGROUND

• 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.

  PMID: 32384914 BACKGROUND

• 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.

  PMID: 28483817 BACKGROUND

• Duerden EG, Grunau RE, Guo T, Foong J, Pearson A, Au-Young S, Lavoie R, Chakravarty MM, Chau V, Synnes A, Miller SP. Early Procedural Pain Is Associated with Regionally-Specific Alterations in Thalamic Development in Preterm Neonates. J Neurosci. 2018 Jan 24;38(4):878-886. doi: 10.1523/JNEUROSCI.0867-17.2017. Epub 2017 Dec 18.

  PMID: 29255007 BACKGROUND

• Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, Claris O, Dempsey E, Franz AR, Fumagalli M, Gluud C, Grevstad B, Hagmann C, Lemmers P, van Oeveren W, Pichler G, Plomgaard AM, Riera J, Sanchez L, Winkel P, Wolf M, Greisen G. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ. 2015 Jan 5;350:g7635. doi: 10.1136/bmj.g7635.

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  PMID: 29930326 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.

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MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn

Interventions

Atropine; Fentanyl

Condition Hierarchy (Ancestors)

Respiratory Distress Syndrome; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Venkatakrishna Kakkilaya, MD

  University of Texas Southwestern Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Quadruple Blinded

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: October 4, 2021
• Study Start: April 6, 2022
• Primary Completion: March 2, 2026
• Study Completion: March 2, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)