Premedication for Less Invasive Surfactant Administration Study (PRELISA)

Respiratory Distress Syndrome, Newborn Clinical Trial

— PRELISA  

Official title:

Use of Premedication for Less Invasive Surfactant Administration: A Randomized Control Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05065424
• Other study ID #: STU-2021-0380
• Status: Recruiting
• Phase: Phase 4
• Start date: March 14, 2022
• Est. completion date: November 2024

Study information

• Verified date: June 2024
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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 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 using cerebral Near Infrared Spectroscopy

• To determine the effect of premedication prior to Less Invasive Surfactant Administration on the need for mechanical ventilation for 24 hours after the procedure

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Hours to 72 Hours

Eligibility

Inclusion Criteria:

• Infants =29 weeks gestational age between 0-72 hours of life on CPAP for respiratory support who qualify for the LISA procedure as determined by the primary team using Parkland OPTISURF guidelines

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

Related Conditions & MeSH terms

• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Parkland Health and Hospital System	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

United States, 

References & Publications (21)

Abdel-Latif ME, Davis PG, Wheeler KI, De Paoli AG, Dargaville PA. Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2021 May 10;5(5):CD011672. doi: 10.1002/14651858.CD011672.pub2. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Johnston L, Kwon SH. Moving from controversy to consensus: premedication for neonatal intubation. J Perinatol. 2018 Jun;38(6):611-613. doi: 10.1038/s41372-018-0115-x. Epub 2018 Jun 22. No abstract available. — View Citation

Klotz D, Porcaro U, Fleck T, Fuchs H. European perspective on less invasive surfactant administration-a survey. Eur J Pediatr. 2017 Feb;176(2):147-154. doi: 10.1007/s00431-016-2812-9. Epub 2016 Dec 9. — View Citation

Kumar P, Denson SE, Mancuso TJ; Committee on Fetus and Newborn, Section on Anesthesiology and Pain Medicine. Premedication for nonemergency endotracheal intubation in the neonate. Pediatrics. 2010 Mar;125(3):608-15. doi: 10.1542/peds.2009-2863. Epub 2010 Feb 22. — 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

Maheshwari R, Tracy M, Badawi N, Hinder M. Neonatal endotracheal intubation: How to make it more baby friendly. J Paediatr Child Health. 2016 May;52(5):480-6. doi: 10.1111/jpc.13192. — View Citation

McPherson C, Grunau RE. Neonatal pain control and neurologic effects of anesthetics and sedatives in preterm infants. Clin Perinatol. 2014 Mar;41(1):209-27. doi: 10.1016/j.clp.2013.10.002. Epub 2013 Dec 17. — View Citation

Rigo V, Lefebvre C, Broux I. Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis. Eur J Pediatr. 2016 Dec;175(12):1933-1942. doi: 10.1007/s00431-016-2789-4. Epub 2016 Sep 27. — View Citation

Stow PJ, McLeod ME, Burrows FA, Creighton RE. Anterior fontanelle pressure responses to tracheal intubation in the awake and anaesthetized infant. Br J Anaesth. 1988 Feb;60(2):167-70. doi: 10.1093/bja/60.2.167. — View Citation

Subramaniam P, Ho JJ, Davis PG. Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2016 Jun 14;(6):CD001243. doi: 10.1002/14651858.CD001243.pub3. — View Citation

Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update. Neonatology. 2019;115(4):432-450. doi: 10.1159/000499361. Epub 2019 Apr 11. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent of time spent with cerebral Near Infrared Spectroscopy (NIRS) values <55%	Cerebral NIRS is a method of noninvasively monitoring cerebral oxygenation. The probes detect a value every 6 seconds and display onto the monitor. Scores between 55-80% are considered within the normal range. Scores less than 55% are considered suboptimal cerebral oxygenation.; Percent of time spent with low NIRS values <55% during the 12 hour observation period will be calculated	From time of start of LISA procedure to 12 hours after procedure
Secondary	Procedure first attempt success rate	Procedure attempt is defined as introduction of laryngoscope blade into the mouth.; Procedure success is defined by ability to insert catheter and administer surfactant, without surfactant aspirated from the stomach after administration.; Rate will be calculated as a percent of participants in each arm.	At time of LISA procedure
Secondary	Intubation rate	Rate will be calculated as a percent of participants in each group.; Participants need for and timing of intubation will be obtained from electronic medical record.	Within 24 hours after LISA procedure
Secondary	Mean number of attempts required	Procedure attempt defined as introduction of laryngoscope blade into the mouth	At time of LISA procedure
Secondary	Mean duration of bradycardia and hypoxemia events	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.; Duration of events in seconds will be recorded by the respiratory therapist and/ or bedside nurse present during the procedure	Time of medication infusion to completion of LISA procedure