<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/NCT04427605</url>
  </required_header>
  <id_info>
    <org_study_id>AOP1795</org_study_id>
    <secondary_id>CESC</secondary_id>
    <nct_id>NCT04427605</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Continuous Infusion of Ketamine in Pediatric Intensive Care Unit (KISS Study)</brief_title>
  <acronym>KISS</acronym>
  <official_title>Efficacy and Safety of Continuous Infusion of Ketamine in Pediatric Intensive Care Unit (KISS Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliera di Padova</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliera di Padova</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study, prospectively evaluate the efficacy and safety of ketamine administered in&#xD;
      continuous infusion lasted more than 12 hours in children admitted to Pediatric Intensive&#xD;
      Care Unit of Padova. This drug may be used as adopted as adopted as adjuvant to analgesia and&#xD;
      sedation or as adjuvant to bronchospasm therapy. The investigators evaluated efficacy&#xD;
      considering the sparing of other analgesics and sedatives and the level of sedation after&#xD;
      ketamine infusion for the first use and the sparing of other bronchospasm drugs sedative&#xD;
      dosage for the second use. To evaluate safety the investigators considered the presence of&#xD;
      adverse effects and onset of withdrawal and delirium syndrome. The study will included al&#xD;
      least 55 pediatric patients &lt; 18 years and mechanically ventilated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ketamine is an N-Methyl-d-aspartate-receptor-antagonist commonly used over the last decades&#xD;
      as an anesthetic and analgesic agent for procedural sedation. The use of ketamine as a&#xD;
      prolonged infusion was first described in 1990 and a prolonged infusion of ketamine has been&#xD;
      described as a successful strategy for analgesia and sedation in patients with hemodynamic&#xD;
      instability, in patients who were mechanically ventilated and poorly responsive to&#xD;
      conventional drugs. An other indication for ketamine infusion is the presence of&#xD;
      bronchospasm, due to its action in promoting bronchodilatation. However, existing studies on&#xD;
      ketamine for prolonged sedation are mainly retrospective and include small sample size,&#xD;
      suggesting that this topic needs to be further investigated. The aim of this observational&#xD;
      single center study is to describe the use of ketamine used as adjuvant to conventional&#xD;
      analgesic and sedative strategy (opioid and benzodiazepine in continuous infusion) as&#xD;
      prolonged infusion (i.e. ≥ 12 hr) in pediatric patients. The investigators will evaluate&#xD;
      ketamine indications, dosages, infusion duration, adoption of boluses, modality of weaning.&#xD;
      Concomitant analgesic and sedative management and monitoring of level of sedation (using a&#xD;
      validated scale) are considered measures of efficacy. Sparing of other bronchospasm drugs&#xD;
      sedative dosage are considered measures of efficacy if ketamine is used in patients with&#xD;
      obstructive respiratory diseases. Presence of adverse effects (including withdrawal syndrome&#xD;
      symptoms and delirium) during infusione or 48 hours after weaning are considered measures of&#xD;
      safety. Data were collected using a standardized data sheet. The study lasted 18 months to&#xD;
      reach a numerosity of 55 patients. All the requested institutional approvals were collected&#xD;
      before starting the data collection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Actual">September 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>level of sedation measured with Comfort Behavior Scale (CBS)</measure>
    <time_frame>12 hours</time_frame>
    <description>CBS score decreased &gt; 2 points after ketamine administration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>incidence adverse effects,delirium and withdrawal syndrome, assessed by physician (also using Cornell Assessment scale of Pediatric Delirium and Withdrawal Assessment tool 1)</measure>
    <time_frame>evaluation during all the duration of ketamine infusion till to 48 hours after the end of it</time_frame>
    <description>incidence of adverse effects and number of patients withf delirium (Cornell Assessment scale of Pediatric Delirium) and withdrawal syndrome (Withdrawal Assessment tool 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>bronchospasm severity</measure>
    <time_frame>12 hours</time_frame>
    <description>change of bronchodilator after ketamine infusion</description>
  </secondary_outcome>
  <other_outcome>
    <measure>presence of hypotension</measure>
    <time_frame>12 hours</time_frame>
    <description>change of inotropic therapy after ketamine infusion</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">57</enrollment>
  <condition>Analgesia</condition>
  <condition>Ketamine Toxicity</condition>
  <condition>Bronchospasm</condition>
  <condition>Sedation Complication</condition>
  <arm_group>
    <arm_group_label>ketamine group</arm_group_label>
    <description>ketamine intravenous infusion in pediatric patients refractory to conventional analgesic-sedative strategy lasted more than 12 hours (dose range 10-50 mcg/Kg/min)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Study population is composed by paediatric patients admitted in PICU treated with ketamine&#xD;
        (lasted more than 12 hours) during mechanical ventilation in the studied period.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pediatric intensive care unit admission&#xD;
&#xD;
          -  mechanical ventilation&#xD;
&#xD;
          -  ketamine infusion &gt; 12 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  parents refusal to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>angela amigoni, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliera di Padova</affiliation>
  </overall_official>
  <overall_official>
    <last_name>andrea pettenazzo, MD</last_name>
    <role>Study Director</role>
    <affiliation>Azienda Ospedaliera di Padova</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedale Università Padova</name>
      <address>
        <city>Padova</city>
        <state>PD</state>
        <zip>35127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Heiberger AL, Ngorsuraches S, Olgun G, Luze L, Leimbach C, Madison H, Lakhani SA. Safety and Utility of Continuous Ketamine Infusion for Sedation in Mechanically Ventilated Pediatric Patients. J Pediatr Pharmacol Ther. 2018 Nov-Dec;23(6):447-454. doi: 10.5863/1551-6776-23.6.447.</citation>
    <PMID>30697129</PMID>
  </reference>
  <reference>
    <citation>Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10.1124/pr.117.015198. Erratum In: Pharmacol Rev. 2018 Oct;70(4):879.</citation>
    <PMID>29945898</PMID>
  </reference>
  <reference>
    <citation>Miller AC, Jamin CT, Elamin EM. Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011 Aug;77(8):812-20.</citation>
    <PMID>21730929</PMID>
  </reference>
  <reference>
    <citation>Golding CL, Miller JL, Gessouroun MR, Johnson PN. Ketamine Continuous Infusions in Critically Ill Infants and Children. Ann Pharmacother. 2016 Mar;50(3):234-41. doi: 10.1177/1060028015626932. Epub 2016 Jan 18.</citation>
    <PMID>26783355</PMID>
  </reference>
  <reference>
    <citation>Neunhoeffer F, Hanser A, Esslinger M, Icheva V, Kumpf M, Gerbig I, Hofbeck M, Michel J. Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study. Paediatr Drugs. 2017 Jun;19(3):259-265. doi: 10.1007/s40272-017-0218-4.</citation>
    <PMID>28299720</PMID>
  </reference>
  <reference>
    <citation>Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005 Jul;46(1):43-50. doi: 10.1016/j.annemergmed.2005.02.024.</citation>
    <PMID>15988425</PMID>
  </reference>
  <reference>
    <citation>Petrillo TM, Fortenberry JD, Linzer JF, Simon HK. Emergency department use of ketamine in pediatric status asthmaticus. J Asthma. 2001 Dec;38(8):657-64. doi: 10.1081/jas-100107543.</citation>
    <PMID>11758894</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>February 12, 2022</last_update_submitted>
  <last_update_submitted_qc>February 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliera di Padova</investigator_affiliation>
    <investigator_full_name>angela amigoni</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>pediatric intensive care unit</keyword>
  <keyword>ketamine</keyword>
  <keyword>sedation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchial Spasm</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT04427605
org study id: AOP1795
secondary id: CESC
nct id: NCT04427605
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study, prospectively evaluate the efficacy and safety of ketamine administered in
      continuous infusion lasted more than 12 hours in children admitted to Pediatric Intensive
      Care Unit of Padova. This drug may be used as adopted as adopted as adjuvant to analgesia and
      sedation or as adjuvant to bronchospasm therapy. The investigators evaluated efficacy
      considering the sparing of other analgesics and sedatives and the level of sedation after
      ketamine infusion for the first use and the sparing of other bronchospasm drugs sedative
      dosage for the second use. To evaluate safety the investigators considered the presence of
      adverse effects and onset of withdrawal and delirium syndrome. The study will included al
      least 55 pediatric patients < 18 years and mechanically ventilated.
Ketamine is an N-Methyl-d-aspartate-receptor-antagonist commonly used over the last decades
      as an anesthetic and analgesic agent for procedural sedation. The use of ketamine as a
      prolonged infusion was first described in 1990 and a prolonged infusion of ketamine has been
      described as a successful strategy for analgesia and sedation in patients with hemodynamic
      instability, in patients who were mechanically ventilated and poorly responsive to
      conventional drugs. An other indication for ketamine infusion is the presence of
      bronchospasm, due to its action in promoting bronchodilatation. However, existing studies on
      ketamine for prolonged sedation are mainly retrospective and include small sample size,
      suggesting that this topic needs to be further investigated. The aim of this observational
      single center study is to describe the use of ketamine used as adjuvant to conventional
      analgesic and sedative strategy (opioid and benzodiazepine in continuous infusion) as
      prolonged infusion (i.e. ≥ 12 hr) in pediatric patients. The investigators will evaluate
      ketamine indications, dosages, infusion duration, adoption of boluses, modality of weaning.
      Concomitant analgesic and sedative management and monitoring of level of sedation (using a
      validated scale) are considered measures of efficacy. Sparing of other bronchospasm drugs
      sedative dosage are considered measures of efficacy if ketamine is used in patients with
      obstructive respiratory diseases. Presence of adverse effects (including withdrawal syndrome
      symptoms and delirium) during infusione or 48 hours after weaning are considered measures of
      safety. Data were collected using a standardized data sheet. The study lasted 18 months to
      reach a numerosity of 55 patients. All the requested institutional approvals were collected
      before starting the data collection.
observational model: Cohort
time perspective: Prospective
measure: level of sedation measured with Comfort Behavior Scale (CBS)
time frame: 12 hours
description: CBS score decreased > 2 points after ketamine administration
measure: incidence adverse effects,delirium and withdrawal syndrome, assessed by physician (also using Cornell Assessment scale of Pediatric Delirium and Withdrawal Assessment tool 1)
time frame: evaluation during all the duration of ketamine infusion till to 48 hours after the end of it
description: incidence of adverse effects and number of patients withf delirium (Cornell Assessment scale of Pediatric Delirium) and withdrawal syndrome (Withdrawal Assessment tool 1)
measure: bronchospasm severity
time frame: 12 hours
description: change of bronchodilator after ketamine infusion
measure: presence of hypotension
time frame: 12 hours
description: change of inotropic therapy after ketamine infusion
arm group label: ketamine group
description: ketamine intravenous infusion in pediatric patients refractory to conventional analgesic-sedative strategy lasted more than 12 hours (dose range 10-50 mcg/Kg/min)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: angela amigoni, MD
role: Principal Investigator
affiliation: Azienda Ospedaliera di Padova
last name: andrea pettenazzo, MD
role: Study Director
affiliation: Azienda Ospedaliera di Padova
facility: 
country: Italy
citation: Heiberger AL, Ngorsuraches S, Olgun G, Luze L, Leimbach C, Madison H, Lakhani SA. Safety and Utility of Continuous Ketamine Infusion for Sedation in Mechanically Ventilated Pediatric Patients. J Pediatr Pharmacol Ther. 2018 Nov-Dec;23(6):447-454. doi: 10.5863/1551-6776-23.6.447.
PMID: 30697129
citation: Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10.1124/pr.117.015198. Erratum In: Pharmacol Rev. 2018 Oct;70(4):879.
PMID: 29945898
citation: Miller AC, Jamin CT, Elamin EM. Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011 Aug;77(8):812-20.
PMID: 21730929
citation: Golding CL, Miller JL, Gessouroun MR, Johnson PN. Ketamine Continuous Infusions in Critically Ill Infants and Children. Ann Pharmacother. 2016 Mar;50(3):234-41. doi: 10.1177/1060028015626932. Epub 2016 Jan 18.
PMID: 26783355
citation: Neunhoeffer F, Hanser A, Esslinger M, Icheva V, Kumpf M, Gerbig I, Hofbeck M, Michel J. Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study. Paediatr Drugs. 2017 Jun;19(3):259-265. doi: 10.1007/s40272-017-0218-4.
PMID: 28299720
citation: Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005 Jul;46(1):43-50. doi: 10.1016/j.annemergmed.2005.02.024.
PMID: 15988425
citation: Petrillo TM, Fortenberry JD, Linzer JF, Simon HK. Emergency department use of ketamine in pediatric status asthmaticus. J Asthma. 2001 Dec;38(8):657-64. doi: 10.1081/jas-100107543.
PMID: 11758894
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliera di Padova
investigator full name: angela amigoni
investigator title: Principal Investigator
mesh term: Bronchial Spasm
sharing ipd: Undecided