Clinical trial NCT04409665: The Use of Sedation Drugs in the Procedure of Administering Surfactant Without Intubation (LISA/MIST)
Official title: The Use of Sedation Drugs in the Procedure of Administering Surfactant Without Intubation (LISA/MIST): a Randomized Study Comparing Intravenous Ketamine With Sublingual 30% Glucose
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Neonatal Respiratory Distress Syndrome
Gestational Age Conditions
Keywords: LISA
LISA sedation
MIST
MIST sedation
Ketamine
Glucose
RDS
Newborn
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2020-06-01
Enrollment: 60
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 60 infants randomized 1:1 to receive ketamine or glucose
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to evaluate the efficacy and impact of intravenous ketamine or sublingual 30% glucose as sedation drugs used in preterm premature babies during the LISA procedure. The second goal is to compare the frequency of complications during LISA with both premedication regimens.

Detailed description: All infants fulfilling the inclusion criteria during the 12 months recruitment window will potentially be enrolled in this randomized controlled trial of LISA premedication. Written informed consent will be acquired from parents or legal guardians. After the consent, infants needing the LISA will receive premedication as follows: caffeine citrate according to the clinical routine at study site, and randomly, either ketamine or sublingual glucose 30%. This study is a pilot study and 60 patients that will be randomized 1:1. Ketamine will be given in slow intravenous injection over 60 seconds. Glucose 30% will be given sublingually in the volume of 1 mL. After two minutes (from the end of administration of the study drug or reference drug), laryngoscopy will be started. To assess the effectiveness of both types of sedation, patients will be assessed using two pain assessment scales - the COMFORT scale and the FANS scale. 10 minutes before the procedure, the first assessment in the COMFORT and FANS scales will take place. The next assessment on both scales will take place during the procedure.

Eligibility criteria: Inclusion Criteria:

* Infant with established Respiratory Distress Syndrome (RDS) or at risk for RDS
* Gestational age 28 0/7 - 32 6/7 weeks
* Non-invasive respiratory support with nasal CPAP (incl. BiPAP) or NIPPV
* Need for administration of exogenous surfactant

Exclusion Criteria:

* Need for intubation and mechanical ventilation at the Delivery Room
* Infant with clinically significant maxillo-facial, tracheal or pulmonary malformations

Primary outcomes:
measure: Assessment of patient sedation
timeFrame: First assessment 10 minutes before procedure, second during the procedure
measure: Assessment of patient sedation
timeFrame: First assessment 10 minutes before procedure, second during the procedure
measure: Comparing ketamine and glucose
timeFrame: Comparing the scores through study completion, an average of two years
measure: Comparing ketamine and glucose
timeFrame: Comparing the scores through study completion, an average of two years
Secondary outcomes:
measure: Frequency of complications
timeFrame: During the procedure
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Uniwersyteckie Centrum Zdrowia Kobiety Noworodka
state: Mazowieckie
Study officials:
affiliation: Medical University of Warsaw
name: Paweł Krajewski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: Dekker J, Lopriore E, Rijken M, Rijntjes-Jacobs E, Smits-Wintjens V, Te Pas A. Sedation during Minimal Invasive Surfactant Therapy in Preterm Infants. Neonatology. 2016;109(4):308-13. doi: 10.1159/000443823. Epub 2016 Feb 24.
citation: McPherson C, Inder T. Perinatal and neonatal use of sedation and analgesia. Semin Fetal Neonatal Med. 2017 Oct;22(5):314-320. doi: 10.1016/j.siny.2017.07.007. Epub 2017 Jul 19.
citation: Allegaert K, van den Anker JN. Neonatal pain management: still in search for the Holy Grail. Int J Clin Pharmacol Ther. 2016 Jul;54(7):514-23. doi: 10.5414/CP202561.
citation: Fernandez C, Boix H, Camba F, Comunas JJ, Castillo F. Less Invasive Surfactant Administration in Spain: A Survey Regarding Its Practice, the Target Population, and Premedication Use. Am J Perinatol. 2020 Feb;37(3):277-280. doi: 10.1055/s-0039-1678534. Epub 2019 Feb 4.
citation: Barrington K. Premedication for endotracheal intubation in the newborn infant. Paediatr Child Health. 2011 Mar;16(3):159-71. doi: 10.1093/pch/16.3.159.
citation: Milesi C, Cambonie G, Jacquot A, Barbotte E, Mesnage R, Masson F, Pidoux O, Ferragu F, Thevenot P, Mariette JB, Picaud JC. Validation of a neonatal pain scale adapted to the new practices in caring for preterm newborns. Arch Dis Child Fetal Neonatal Ed. 2010 Jul;95(4):F263-6. doi: 10.1136/adc.2008.144758. Epub 2009 Feb 16.