<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/NCT02249039</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00109563</org_study_id>
    <nct_id>NCT02249039</nct_id>
  </id_info>
  <brief_title>Intravenous Clonidine for Sedation in Infants and Children Who Are Mechanically Ventilated - Dosing Finding Study</brief_title>
  <official_title>Intravenous Clonidine for Sedation in Infants and Children Who Are Mechanically Ventilated - Dosing Finding Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      Critically ill infants and children who are mechanically ventilated are often given large&#xD;
      doses of opiates and benzodiazepines to provide analgesia-sedation. These drugs significantly&#xD;
      cause tolerance and dependence, depresses the drive to breathe, and thus prolongs the need&#xD;
      for mechanical ventilation and the associated complications. We propose IV CLON could be used&#xD;
      as effectively as DEX.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All critically ill mechanically ventilated infants and children receive intravenous&#xD;
      analgesic-sedatives which often include opiates and benzodiazepines (BENZO). Undesirable side&#xD;
      effects from these drugs include respiratory depression, tolerance and dependence. Alpha&#xD;
      2-adrenergic receptor agonists, dexmedetomidine (DEX) and clonidine (CLON) have excellent&#xD;
      sedative-analgesics effects, do not cause respiratory depression and are opiate/BENZO&#xD;
      sparing. While both are efficacious in providing sedation, several factors have led to a&#xD;
      substantial increase in the use of the newer drug DEX over the more established drug CLON in&#xD;
      adults, children and infants. However, studies to guide therapy and dosing for infants and&#xD;
      children are lacking. While these infants and children do require less opiate/BENZO therapy&#xD;
      and fewer days on mechanical ventilation, they quickly develop tolerance to and have&#xD;
      significant withdrawal from DEX. This necessitates protracted weaning of DEX and longer&#xD;
      length of stay in the pediatric intensive care unit (PICU) since DEX can only be administered&#xD;
      as a continuous intravenous (IV) infusion. CLON, on the other hand, has a longer half-life&#xD;
      and has formulations that allow for continuous or intermittent IV and oral administration.&#xD;
      Dr. Gauda has an approved IND to use the epidural formulation of CLON intravenously in&#xD;
      infants and children. The purpose of this pilot study is to determine the effective IV dosing&#xD;
      scheme of CLON that can be safely used as an adjunct to analgesic-sedation management for&#xD;
      infants and children in the PICU. It will include a total of 24 infants and children with 4&#xD;
      CLON and DEX exposed in each age stratum: 0-3, 4-6, and 7-12 months. We hypothesize that IV&#xD;
      CLON can achieve optimal sedation and reduce the need for opiate/BENZO therapy in critically&#xD;
      ill infants and children who would otherwise receive DEX, and thus, reduce the length of stay&#xD;
      in the PICU. Data from this study will be used to inform a larger randomized trial and will&#xD;
      directly benefit infants and children in Baltimore who are critically ill. Funds are&#xD;
      requested to cover the cost of the CLON drug levels and the investigational pharmacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2015</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sedation</measure>
    <time_frame>2-8 weeks</time_frame>
    <description>Time spent (hrs) with a State Behavioral Scale &lt;1 without the concurrent escalation of opiates or sedatives within 24 hrs after starting the CLON or DEX</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of cardiovascular occurrences</measure>
    <time_frame>2 - 8 weeks</time_frame>
    <description>Frequency of cardiovascular occurrences i. ≥10 torr reduction in mean arterial blood pressure (MAP) ii. 20% drop in HR from the infant's baseline iii. Changes in HR or Blood pressure that triggers an intervention by the clinical team such as: -&#xD;
Adding or escalating cardiotonic meds&#xD;
holding the dose of timed sedative/analgesia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay</measure>
    <time_frame>2-8 weeks</time_frame>
    <description>Length of stay in PICU for sedative-analgesic therapy after stabilization and extubation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Mechanical Ventilation Complication</condition>
  <arm_group>
    <arm_group_label>intermittent IV CLON</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mechanically ventilated infants and children receive intravenous intermittentClonidine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>intermittent IV CLON</intervention_name>
    <description>Mechanically ventilated infants and children receive intravenous intermittent Clonidine instead of dexmedetomidine</description>
    <arm_group_label>intermittent IV CLON</arm_group_label>
    <other_name>clonidine hydrochloride</other_name>
    <other_name>Duraclon</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants and children age: 0-12 months&#xD;
&#xD;
          -  Intubated and mechanically ventilated in the JHH PICU&#xD;
&#xD;
          -  Meet criteria for starting dexmedetomidine (per PICU protocol)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Postoperative from complex congenital heart disease&#xD;
&#xD;
          -  Asphyxia&#xD;
&#xD;
          -  Traumatic Brain Injury&#xD;
&#xD;
          -  Major Chromosomal anomaly (Trisomy 13, 18)&#xD;
&#xD;
          -  Any infant or child who is receiving ECMO therapy&#xD;
&#xD;
          -  If death is considered imminent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sapna R Kudchadkar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>February 26, 2021</last_update_submitted>
  <last_update_submitted_qc>February 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clonidine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02249039
org study id: IRB00109563
nct id: NCT02249039
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
Critically ill infants and children who are mechanically ventilated are often given large
      doses of opiates and benzodiazepines to provide analgesia-sedation. These drugs significantly
      cause tolerance and dependence, depresses the drive to breathe, and thus prolongs the need
      for mechanical ventilation and the associated complications. We propose IV CLON could be used
      as effectively as DEX.
All critically ill mechanically ventilated infants and children receive intravenous
      analgesic-sedatives which often include opiates and benzodiazepines (BENZO). Undesirable side
      effects from these drugs include respiratory depression, tolerance and dependence. Alpha
      2-adrenergic receptor agonists, dexmedetomidine (DEX) and clonidine (CLON) have excellent
      sedative-analgesics effects, do not cause respiratory depression and are opiate/BENZO
      sparing. While both are efficacious in providing sedation, several factors have led to a
      substantial increase in the use of the newer drug DEX over the more established drug CLON in
      adults, children and infants. However, studies to guide therapy and dosing for infants and
      children are lacking. While these infants and children do require less opiate/BENZO therapy
      and fewer days on mechanical ventilation, they quickly develop tolerance to and have
      significant withdrawal from DEX. This necessitates protracted weaning of DEX and longer
      length of stay in the pediatric intensive care unit (PICU) since DEX can only be administered
      as a continuous intravenous (IV) infusion. CLON, on the other hand, has a longer half-life
      and has formulations that allow for continuous or intermittent IV and oral administration.
      Dr. Gauda has an approved IND to use the epidural formulation of CLON intravenously in
      infants and children. The purpose of this pilot study is to determine the effective IV dosing
      scheme of CLON that can be safely used as an adjunct to analgesic-sedation management for
      infants and children in the PICU. It will include a total of 24 infants and children with 4
      CLON and DEX exposed in each age stratum: 0-3, 4-6, and 7-12 months. We hypothesize that IV
      CLON can achieve optimal sedation and reduce the need for opiate/BENZO therapy in critically
      ill infants and children who would otherwise receive DEX, and thus, reduce the length of stay
      in the PICU. Data from this study will be used to inform a larger randomized trial and will
      directly benefit infants and children in Baltimore who are critically ill. Funds are
      requested to cover the cost of the CLON drug levels and the investigational pharmacy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sedation
time frame: 2-8 weeks
description: Time spent (hrs) with a State Behavioral Scale <1 without the concurrent escalation of opiates or sedatives within 24 hrs after starting the CLON or DEX
measure: Frequency of cardiovascular occurrences
time frame: 2 - 8 weeks
description: Frequency of cardiovascular occurrences i. ≥10 torr reduction in mean arterial blood pressure (MAP) ii. 20% drop in HR from the infant's baseline iii. Changes in HR or Blood pressure that triggers an intervention by the clinical team such as: -
Adding or escalating cardiotonic meds
holding the dose of timed sedative/analgesia
measure: Length of stay
time frame: 2-8 weeks
description: Length of stay in PICU for sedative-analgesic therapy after stabilization and extubation.
arm group label: intermittent IV CLON
arm group type: Experimental
description: Mechanically ventilated infants and children receive intravenous intermittentClonidine
intervention type: Drug
intervention name: intermittent IV CLON
description: Mechanically ventilated infants and children receive intravenous intermittent Clonidine instead of dexmedetomidine
arm group label: intermittent IV CLON
other name: clonidine hydrochloride
other name: Duraclon
criteria: 
gender: All
minimum age: 1 Day
maximum age: 12 Months
healthy volunteers: No
last name: Sapna R Kudchadkar, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Clonidine