<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/NCT02216266</url>
  </required_header>
  <id_info>
    <org_study_id>DELIcu</org_study_id>
    <secondary_id>2012-004082-41</secondary_id>
    <nct_id>NCT02216266</nct_id>
  </id_info>
  <brief_title>Evaluation if Physostigmine Reduces Symptoms in Patients Who Has Developed a Delirium in Intensive Care After a Surgery</brief_title>
  <official_title>Monocenter, Double Blind, Randomised, Placebo Controlled Study to Evaluate Physostigmine for the Treatment of Delirium in Perioperative Intensive Care Medicine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PD Dr. Bertram Scheller</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Goethe University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dr. Franz Köhler Chemie GmbH (study medication and labeling)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Johann Wolfgang Goethe University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluation if physostigmine reduces symptoms in patients who has developed a delirium in&#xD;
      Intensive care after a surgery&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2014</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change of vigilance or symptoms of the delirium measured by Richmond Agitation Sedation Score (RASS)</measure>
    <time_frame>baseline to 48 hours after administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>reduction of weaning time at mechanical ventilator of patients with symptoms of delirium</measure>
    <time_frame>baseline to 48 hours after administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in the spontaneous EEG and auditory evoked potentials</measure>
    <time_frame>baseline to 48 hours after administration</time_frame>
    <description>for the spontaneous EEG, we expect a shift in the frequency characteristics, measure is the spectrogram, more precisely the amplitude per frequency (band) and the phase information derived via Fourier Transform and Wavelet transformation&#xD;
The paradigm of the auditory stimulation is a roving paradigm (Science 13 May 2011:&#xD;
Vol. 332 no. 6031 pp. 858-862 DOI: 10.1126/science.1202043&#xD;
•Report Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State Melanie Boly1,2,*, Marta Isabel Garrido2, Olivia Gosseries1, Marie-Aurélie Bruno1, Pierre Boveroux3, Caroline Schnakers1, Marcello Massimini4, Vladimir Litvak2, Steven Laureys1, Karl Friston2) Measures will be differences in the mismatch negativity and in the phase synchronization between electrodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>impact of the variability of heart rate</measure>
    <time_frame>baseline to 48 hours</time_frame>
    <description>heart rate variability is a dimensionless parameter, assessing the variability of the heart rate from ECG measures (Heart Rate Variability Conny M. A. van Ravenswaaij-Arts, MD; Louis A. A. Kollee, MD, PhD; Jeroen C. W. Hopman, MSc; Gerard B. A. Stoelinga, MD, PhD; and Herman P. van Geijn, MD, PhD [+-] Article and Author Information&#xD;
Ann Intern Med. 1993;118(6):436-447. doi:10.7326/0003-4819-118-6-199303150-00008 )</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in development of muscular force</measure>
    <time_frame>baseline up to 48 hours</time_frame>
    <description>muscular force is measured with a force gauge, measured in [Newton]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence of Adverse events</measure>
    <time_frame>baseline to 4 weeks after treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Suspected Delirium After Elective or Emergency Heart Surgery</condition>
  <condition>CAM-ICU Diagnosed Delirium</condition>
  <arm_group>
    <arm_group_label>Physostigmine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Physostigmine administered intravenously at a dose of 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sodium Chloride solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>solution administered intravenously 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Physostigmine</intervention_name>
    <arm_group_label>Physostigmine</arm_group_label>
    <other_name>Anticholium</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sodium Chloride solution</intervention_name>
    <arm_group_label>Sodium Chloride solution</arm_group_label>
    <other_name>NaCl solution as Placebo comparator</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients of both genders aged &gt; 18 years, &lt; 85 years of ICU C1 after elective or&#xD;
             emergency heart surgery with or without extracorporeal circulation (heart-lung machine&#xD;
             and/or extracorporeal membrane oxygenation), with suspected delirium. (May be&#xD;
             suspected if a patient does not show adequate improvement of vigilance 24 h after&#xD;
             adequate reduction or stop of sedative medicine)&#xD;
&#xD;
          -  Patients (&gt;18a, &lt;85a) with CAM-ICU diagnosed delirium&#xD;
&#xD;
          -  Patients of legal capacity and patients with appointed representative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Asthma&#xD;
&#xD;
          -  hypersensitivity against Physostigmine salicylate, Sodium metabisulfite, Nitrogen&#xD;
&#xD;
          -  gangrene mechanical obstipation&#xD;
&#xD;
          -  mechanical urinary retention&#xD;
&#xD;
          -  Dystrophia myotonica&#xD;
&#xD;
          -  Depolarization block after depolarising muscle relaxants&#xD;
&#xD;
          -  Intoxications with &quot;irreversibly acting&quot; cholinesterase inhibitors&#xD;
&#xD;
          -  closed head trauma&#xD;
&#xD;
          -  obstructions at gastro-intestinal tract and at urinary tract&#xD;
&#xD;
          -  neurological diseases&#xD;
&#xD;
          -  left ventricular ejection fraction &lt; 40%&#xD;
&#xD;
          -  Simultaneous Participation in other clinical trials or participation ind other&#xD;
             clinical trials in the last 30 days&#xD;
&#xD;
          -  untreated coronary heart disease&#xD;
&#xD;
          -  wish to have children, pregnancy or nursing&#xD;
&#xD;
          -  patients with addictive disorder in medical history&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bertram Scheller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy of Goethe-University Frankfurt</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bertram Scheller, MD</last_name>
    <email>bertram.scheller@kgu.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessia</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Bertram Scheller, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>October 17, 2013</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>March 9, 2017</last_update_submitted>
  <last_update_submitted_qc>March 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Johann Wolfgang Goethe University Hospital</investigator_affiliation>
    <investigator_full_name>PD Dr. Bertram Scheller</investigator_full_name>
    <investigator_title>PD MD Bertram Scheller</investigator_title>
  </responsible_party>
  <keyword>Delirium</keyword>
  <keyword>CAM-ICU</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Emergencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pharmaceutical Solutions</mesh_term>
    <mesh_term>Physostigmine</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/NCT02216266
org study id: DELIcu
secondary id: 2012-004082-41
nct id: NCT02216266
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Evaluation if physostigmine reduces symptoms in patients who has developed a delirium in
      Intensive care after a surgery
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: change of vigilance or symptoms of the delirium measured by Richmond Agitation Sedation Score (RASS)
time frame: baseline to 48 hours after administration
measure: reduction of weaning time at mechanical ventilator of patients with symptoms of delirium
time frame: baseline to 48 hours after administration
measure: change in the spontaneous EEG and auditory evoked potentials
time frame: baseline to 48 hours after administration
description: for the spontaneous EEG, we expect a shift in the frequency characteristics, measure is the spectrogram, more precisely the amplitude per frequency (band) and the phase information derived via Fourier Transform and Wavelet transformation
The paradigm of the auditory stimulation is a roving paradigm (Science 13 May 2011:
Vol. 332 no. 6031 pp. 858-862 DOI: 10.1126/science.1202043
•Report Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State Melanie Boly1,2,*, Marta Isabel Garrido2, Olivia Gosseries1, Marie-Aurélie Bruno1, Pierre Boveroux3, Caroline Schnakers1, Marcello Massimini4, Vladimir Litvak2, Steven Laureys1, Karl Friston2) Measures will be differences in the mismatch negativity and in the phase synchronization between electrodes
measure: impact of the variability of heart rate
time frame: baseline to 48 hours
description: heart rate variability is a dimensionless parameter, assessing the variability of the heart rate from ECG measures (Heart Rate Variability Conny M. A. van Ravenswaaij-Arts, MD; Louis A. A. Kollee, MD, PhD; Jeroen C. W. Hopman, MSc; Gerard B. A. Stoelinga, MD, PhD; and Herman P. van Geijn, MD, PhD [+-] Article and Author Information
Ann Intern Med. 1993;118(6):436-447. doi:10.7326/0003-4819-118-6-199303150-00008 )
measure: change in development of muscular force
time frame: baseline up to 48 hours
description: muscular force is measured with a force gauge, measured in [Newton]
measure: Occurence of Adverse events
time frame: baseline to 4 weeks after treatment
arm group label: Physostigmine
arm group type: Active Comparator
description: Physostigmine administered intravenously at a dose of 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram
arm group label: Sodium Chloride solution
arm group type: Placebo Comparator
description: solution administered intravenously 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram
intervention type: Drug
intervention name: Physostigmine
arm group label: Physostigmine
other name: Anticholium
intervention type: Other
intervention name: Sodium Chloride solution
arm group label: Sodium Chloride solution
other name: NaCl solution as Placebo comparator
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Bertram Scheller, MD
role: Principal Investigator
affiliation: Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy of Goethe-University Frankfurt
last name: Bertram Scheller, MD
email: bertram.scheller@kgu.de
facility: 
status: Recruiting
investigator: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: Johann Wolfgang Goethe University Hospital
investigator full name: PD Dr. Bertram Scheller
investigator title: PD MD Bertram Scheller
mesh term: Delirium
mesh term: Emergencies
mesh term: Pharmaceutical Solutions
mesh term: Physostigmine