<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04409665</url>
  </required_header>
  <id_info>
    <org_study_id>LISA KGS TRIAL 2020</org_study_id>
    <nct_id>NCT04409665</nct_id>
  </id_info>
  <brief_title>The Use of Sedation Drugs in the Procedure of Administering Surfactant Without Intubation (LISA/MIST)</brief_title>
  <acronym>LISA KGS</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Warsaw</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and impact of intravenous ketamine or&#xD;
      sublingual 30% glucose as sedation drugs used in preterm premature babies during the LISA&#xD;
      procedure. The second goal is to compare the frequency of complications during LISA with both&#xD;
      premedication regimens.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All infants fulfilling the inclusion criteria during the 12 months recruitment window will&#xD;
      potentially be enrolled in this randomized controlled trial of LISA premedication. Written&#xD;
      informed consent will be acquired from parents or legal guardians. After the consent, infants&#xD;
      needing the LISA will receive premedication as follows: caffeine citrate according to the&#xD;
      clinical routine at study site, and randomly, either ketamine or sublingual glucose 30%. This&#xD;
      study is a pilot study and 60 patients that will be randomized 1:1. Ketamine will be given in&#xD;
      slow intravenous injection over 60 seconds. Glucose 30% will be given sublingually in the&#xD;
      volume of 1 mL. After two minutes (from the end of administration of the study drug or&#xD;
      reference drug), laryngoscopy will be started. To assess the effectiveness of both types of&#xD;
      sedation, patients will be assessed using two pain assessment scales - the COMFORT scale and&#xD;
      the FANS scale. 10 minutes before the procedure, the first assessment in the COMFORT and FANS&#xD;
      scales will take place. The next assessment on both scales will take place during the&#xD;
      procedure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>60 infants randomized 1:1 to receive ketamine or glucose</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of patient sedation</measure>
    <time_frame>First assessment 10 minutes before procedure, second during the procedure</time_frame>
    <description>Assessment of patient sedation change before and after LISA using COMFORT scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of patient sedation</measure>
    <time_frame>First assessment 10 minutes before procedure, second during the procedure</time_frame>
    <description>Assessment of patient sedation change before and after LISA using FANS scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparing ketamine and glucose</measure>
    <time_frame>Comparing the scores through study completion, an average of two years</time_frame>
    <description>Comparison of the effectiveness of sedation with ketamine and glucose using the FANS scale scores. The FANS scale ranges from 0 points at minimum to 10 points at maximum. The higher the score, the lower the sedation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparing ketamine and glucose</measure>
    <time_frame>Comparing the scores through study completion, an average of two years</time_frame>
    <description>Comparison of the effectiveness of sedation with ketamine and glucose using the COMFORT scale scores. The Comfort scale ranges from 8 points at minimum, to 40 at maximum. The higher the score, the lower the sedation level.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of complications</measure>
    <time_frame>During the procedure</time_frame>
    <description>Monitoring the possible side effects of used drugs</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Neonatal Respiratory Distress Syndrome</condition>
  <condition>Gestational Age Conditions</condition>
  <arm_group>
    <arm_group_label>Ketamine sedated group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 randomized patients will receive Ketamine 1 mg/kg , I.V. 2 minutes before LISA</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glucose sedated group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30 patients will receive Glucose 30% 1 mL, sublingually, 2 minutes before LISA</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Patient will be sedated using Ketamine 2 minutes before the LISA procedure. 10 minutes prior the procedure and during the procedure the patient's pain and/or discomfort will be evaluated using COMFORT and FANS scales</description>
    <arm_group_label>Ketamine sedated group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glucose</intervention_name>
    <description>Patient will be sedated using Glucose 2 minutes before the LISA procedure. 10 minutes prior the procedure and during the procedure the patient's pain and/or discomfort will be evaluated using COMFORT and FANS scales</description>
    <arm_group_label>Glucose sedated group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infant with established Respiratory Distress Syndrome (RDS) or at risk for RDS&#xD;
&#xD;
          -  Gestational age 28 0/7 - 32 6/7 weeks&#xD;
&#xD;
          -  Non-invasive respiratory support with nasal CPAP (incl. BiPAP) or NIPPV&#xD;
&#xD;
          -  Need for administration of exogenous surfactant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Need for intubation and mechanical ventilation at the Delivery Room&#xD;
&#xD;
          -  Infant with clinically significant maxillo-facial, tracheal or pulmonary malformations&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Minute</minimum_age>
    <maximum_age>4 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paweł Krajewski, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Warsaw</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tomasz Piotr Pomianek, MD</last_name>
    <phone>502536300</phone>
    <phone_ext>+48</phone_ext>
    <email>tomek.pomianek@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Paweł Krajewski, MD, PhD</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Zdrowia Kobiety Noworodka</name>
      <address>
        <city>Warsaw</city>
        <state>Mazowieckie</state>
        <zip>02-015</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tomasz Pomianek, MD</last_name>
      <phone>502536300</phone>
      <phone_ext>+48</phone_ext>
      <email>tomek.pomianek@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Paweł Krajewski, PhD, MD</last_name>
      <email>pawelkrajewski@outlook.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <reference>
    <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>
    <PMID>24524456</PMID>
  </reference>
  <reference>
    <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>
    <PMID>30635595</PMID>
  </reference>
  <reference>
    <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>
    <PMID>29532502</PMID>
  </reference>
  <reference>
    <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>
    <PMID>26907795</PMID>
  </reference>
  <reference>
    <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>
    <PMID>28734732</PMID>
  </reference>
  <reference>
    <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>
    <PMID>27087155</PMID>
  </reference>
  <reference>
    <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>
    <PMID>30716788</PMID>
  </reference>
  <reference>
    <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>
    <PMID>22379381</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19221401</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>January 16, 2022</last_update_submitted>
  <last_update_submitted_qc>January 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Warsaw</investigator_affiliation>
    <investigator_full_name>PAWEL KRAJEWSKI, MD</investigator_full_name>
    <investigator_title>Head of the division of neonatology</investigator_title>
  </responsible_party>
  <keyword>LISA</keyword>
  <keyword>LISA sedation</keyword>
  <keyword>MIST</keyword>
  <keyword>MIST sedation</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Glucose</keyword>
  <keyword>RDS</keyword>
  <keyword>Newborn</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Hyaline Membrane Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All of the individual participant data collected during the trial will be available, after de-identification. The study protocol will also be available. These documents will be accessible to anyone who provides a methodologically sound proposal immediately following publication with no end date.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Immediately following publication. No end date.</ipd_time_frame>
    <ipd_access_criteria>Anyone who provides a methodologically sound proposal.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04409665
org study id: LISA KGS TRIAL 2020
nct id: NCT04409665
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 60 infants randomized 1:1 to receive ketamine or glucose
primary purpose: Supportive Care
masking: None (Open Label)
measure: Assessment of patient sedation
time frame: First assessment 10 minutes before procedure, second during the procedure
description: Assessment of patient sedation change before and after LISA using COMFORT scale
measure: Assessment of patient sedation
time frame: First assessment 10 minutes before procedure, second during the procedure
description: Assessment of patient sedation change before and after LISA using FANS scale
measure: Comparing ketamine and glucose
time frame: Comparing the scores through study completion, an average of two years
description: Comparison of the effectiveness of sedation with ketamine and glucose using the FANS scale scores. The FANS scale ranges from 0 points at minimum to 10 points at maximum. The higher the score, the lower the sedation.
measure: Comparing ketamine and glucose
time frame: Comparing the scores through study completion, an average of two years
description: Comparison of the effectiveness of sedation with ketamine and glucose using the COMFORT scale scores. The Comfort scale ranges from 8 points at minimum, to 40 at maximum. The higher the score, the lower the sedation level.
measure: Frequency of complications
time frame: During the procedure
description: Monitoring the possible side effects of used drugs
arm group label: Ketamine sedated group
arm group type: Experimental
description: 30 randomized patients will receive Ketamine 1 mg/kg , I.V. 2 minutes before LISA
arm group label: Glucose sedated group
arm group type: Active Comparator
description: 30 patients will receive Glucose 30% 1 mL, sublingually, 2 minutes before LISA
intervention type: Drug
intervention name: Ketamine
description: Patient will be sedated using Ketamine 2 minutes before the LISA procedure. 10 minutes prior the procedure and during the procedure the patient's pain and/or discomfort will be evaluated using COMFORT and FANS scales
arm group label: Ketamine sedated group
intervention type: Drug
intervention name: Glucose
description: Patient will be sedated using Glucose 2 minutes before the LISA procedure. 10 minutes prior the procedure and during the procedure the patient's pain and/or discomfort will be evaluated using COMFORT and FANS scales
arm group label: Glucose sedated group
criteria: 
gender: All
minimum age: 1 Minute
maximum age: 4 Months
healthy volunteers: No
last name: Paweł Krajewski, MD, PhD
role: Principal Investigator
affiliation: Medical University of Warsaw
last name: Tomasz Piotr Pomianek, MD
phone: 502536300
phone ext: +48
email: tomek.pomianek@gmail.com
last name: Paweł Krajewski, MD, PhD
facility: 
status: Recruiting
contact: 
contact backup: 
country: Poland
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.
PMID: 24524456
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.
PMID: 30635595
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.
PMID: 29532502
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.
PMID: 26907795
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.
PMID: 28734732
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.
PMID: 27087155
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.
PMID: 30716788
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.
PMID: 22379381
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.
PMID: 19221401
responsible party type: Principal Investigator
investigator affiliation: Medical University of Warsaw
investigator full name: PAWEL KRAJEWSKI, MD
investigator title: Head of the division of neonatology
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Hyaline Membrane Disease
mesh term: Ketamine
sharing ipd: Yes
ipd description: All of the individual participant data collected during the trial will be available, after de-identification. The study protocol will also be available. These documents will be accessible to anyone who provides a methodologically sound proposal immediately following publication with no end date.
ipd info type: Study Protocol
ipd time frame: Immediately following publication. No end date.
ipd access criteria: Anyone who provides a methodologically sound proposal.