<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/NCT03795623</url>
  </required_header>
  <id_info>
    <org_study_id>417_18 B</org_study_id>
    <nct_id>NCT03795623</nct_id>
  </id_info>
  <brief_title>Voices of Patients' Relatives to Support Weaning From Mechanical Ventilation</brief_title>
  <acronym>VOICE-WEANING</acronym>
  <official_title>Voices of Patients' Relatives to Support Weaning From Mechanical Ventilation in Patients With Severe Brain Injury - VOICE-WEANING, a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Erlangen-Nürnberg Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Erlangen-Nürnberg Medical School</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>
      Patients with severe brain injuries, such as ischemic stroke and intracranial hemorrhage,&#xD;
      frequently require mechanical ventilation. Weaning of stroke patients is complicated by&#xD;
      impaired consciousness and respiratory drive. Higher rates of weaning failure and delayed&#xD;
      extubation (≥ 48h) lead to ventilator associated pneumonia, higher mortality and necessity of&#xD;
      tracheostomy.&#xD;
&#xD;
      Therefore, improving the weaning of stroke patients from mechanical ventilation is warranted&#xD;
      to prevent ventilator-associated complications and eventually improve clinical outcomes.&#xD;
&#xD;
      This single-center, randomized, clinical trial aims at demonstrating that voices of patients'&#xD;
      relatives support weaning from mechanical ventilation and reduce weaning failure in&#xD;
      brain-injured patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methods: Adult ICU-patients with controlled mechanical ventilation ≥48h due to a neurological&#xD;
      disease will be included in the intensive care unit. A predefined text - including&#xD;
      information on the patient's condition and recurrent request to breath in and out - will be&#xD;
      recorded as an audio file by one of the patient's relatives. Patients will be randomly&#xD;
      assigned in a 1:1 ratio to the conventional treatment arm or the Voice-Weaning arm. In the&#xD;
      conventional arm, audio recordings will be muted by an independent person resulting in a mute&#xD;
      recording without audio signals.&#xD;
&#xD;
      When conversion from controlled to assisted mechanical ventilation is intended according to&#xD;
      standard treatment, audio recordings will be administered in repeat mode for 10 minutes and&#xD;
      performed three times per day. If spontaneous breathing trials (SBT) are intended according&#xD;
      to standard treatment, the audio recordings will be played during the SBT three times per&#xD;
      day.&#xD;
&#xD;
      Criteria for weaning not to be intended - according to Boles et al. (Weaning from mechanical&#xD;
      ventilation. Eur Respir J. 2007) and adapted to neurological patients:&#xD;
&#xD;
      Objective measurements:&#xD;
&#xD;
        -  Unstable clinical condition&#xD;
&#xD;
             -  Cardiovascular status (fC≥140/min, systolic BP &lt;90mmHg or &gt;180mmHg, more than&#xD;
                minimal vasopressors)&#xD;
&#xD;
             -  Metabolic status (e.g. inacceptable electrolytes)&#xD;
&#xD;
        -  Inadequate oxygenation&#xD;
&#xD;
             -  SaO2 ≤90% on FiO2 &gt;40% or pO2/FiO2 &lt;150mmHg or pO2/FiO2 &lt;120mmHg in case of chronic&#xD;
                hypoxemia (Horowitz index)&#xD;
&#xD;
             -  PEEP&gt;8cmH2O&#xD;
&#xD;
        -  Inadequate pulmonary function&#xD;
&#xD;
             -  fR ≥35/min&#xD;
&#xD;
             -  MIP&gt;(-20 -) -25cmH2O&#xD;
&#xD;
             -  VT ≤5ml/kgKG&#xD;
&#xD;
             -  VC ≤10ml/kgKG&#xD;
&#xD;
             -  fR/VT ≥105 breaths/min x l (RSBI)&#xD;
&#xD;
             -  significant respiratory acidosis (pH≤7.25)&#xD;
&#xD;
        -  Unstable neurological condition&#xD;
&#xD;
             -  sedation or inadequate mentation on sedation&#xD;
&#xD;
             -  present or anticipated intracranial mass effect (e.g. midline shift &gt;10mm or&#xD;
                progression, basal cistern effacement or oculomotor disturbance, signs of&#xD;
                transfalxial/transtentorial/transforaminal herniation&#xD;
&#xD;
             -  elevation of intracranial pressure (&gt;20 cmH2O) and/or obstructive hydrocephalus&#xD;
&#xD;
             -  severe vasospasms (&gt;6 kHz in transcranial Doppler, or determined by CT-A/CT-P)&#xD;
&#xD;
             -  status epilepticus (determined by EEG)&#xD;
&#xD;
             -  acute intracranial infection (without established and/or treated origin)&#xD;
&#xD;
      Clinical assessment:&#xD;
&#xD;
        -  Inadequate cough&#xD;
&#xD;
        -  Excessive tracheobronchial secretion&#xD;
&#xD;
        -  Disease acute phase for which the patient was intubated&#xD;
&#xD;
      Ethics Approval: The Institutional Review Board of the Friedrich-Alexander-Universität&#xD;
      Erlangen-Nürnberg approved of the study on 13 November 2018.&#xD;
&#xD;
      Sample Size Calculation: The sample size is computed with 80% power and a 5% α-risk for the&#xD;
      hypothesis of Voice Weaning achieving a 15% absolute weaning failure reduction. The sample&#xD;
      size is increased by 10% to correct for dropouts and lost to follow up: a maximum of 354&#xD;
      patients will be included and an interim analysis be performed after inclusion of 50% of the&#xD;
      calculated subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">January 31, 2021</primary_completion_date>
  <phase>N/A</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 (Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of weaning failure</measure>
    <time_frame>first 28 days after start of ventilation, or until 48 hours after extubation, or discharge from intensive care, whichever came first</time_frame>
    <description>Reintubation and/or resumption of ventilatory support following extubation or death following extubation or failed spontaneous breathing trial</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time of controlled ventilation</measure>
    <time_frame>first 28 days after start of ventilation or discharge from intensive care, whichever came first</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of tracheotomy</measure>
    <time_frame>first 28 days after start of ventilation or discharge from intensive care, whichever came first</time_frame>
    <description>Proportion of patients requiring tracheotomy performed as percutaneous dilatative tracheotomy or surgical tracheotomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All cause mortality rate at 90 days</measure>
    <time_frame>first 90 days after start of ventilation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of ICU delirium</measure>
    <time_frame>first 28 days after start of ventilation or discharge from intensive care, whichever came first</time_frame>
    <description>Development of delirium according to the Confusion Assessment Method for intensive care unit (CAM-ICU)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Ventilator Weaning</condition>
  <condition>Weaning Failure</condition>
  <condition>Brain Injuries</condition>
  <arm_group>
    <arm_group_label>Conventional arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Muted audio recordings of the patients relatives.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Voice-Weaning arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Audio recordings of the patients relatives including information on the patient's condition and recurrent request to breath in and out.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Voice-Weaning</intervention_name>
    <description>Audio recordings of patients' relatives for 10 minutes x 3 daily from initiation of assisted mechanical ventilation to extubation or ICU discharge.</description>
    <arm_group_label>Voice-Weaning arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham control</intervention_name>
    <description>Muted audio recordings of patients' relatives for 10 minutes x 3 daily from initiation of assisted mechanical ventilation to extubation or ICU discharge.</description>
    <arm_group_label>Conventional arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Intubation and controlled mechanical ventilation ≥48h due to a neurological disease&#xD;
&#xD;
          -  Weaning from mechanical ventilation intended by the attending physician&#xD;
&#xD;
          -  Obtained informed consent from the legal representative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  History of psychiatric disease&#xD;
&#xD;
          -  Weaning from mechanical ventilation not intended or decision to limit therapeutic&#xD;
             interventions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hagen B. Huttner, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Erlangen-Nürnberg Medical School, Department of Neurology, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joji B. Kuramatsu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Erlangen-Nürnberg Medical School, Department of Neurology, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maximilian I. Sprügel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Erlangen-Nürnberg Medical School, Department of Neurology, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Giessen</name>
      <address>
        <city>Gießen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>January 31, 2023</last_update_submitted>
  <last_update_submitted_qc>January 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Erlangen-Nürnberg Medical School</investigator_affiliation>
    <investigator_full_name>Hagen B. Huttner</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Critical Illness</keyword>
  <keyword>Respiration Disorder</keyword>
  <keyword>Neurology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Because of local ethics committees restrictions the final decision upon release of the raw data has not been made.</ipd_description>
  </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/NCT03795623
org study id: 417_18 B
nct id: NCT03795623
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with severe brain injuries, such as ischemic stroke and intracranial hemorrhage,
      frequently require mechanical ventilation. Weaning of stroke patients is complicated by
      impaired consciousness and respiratory drive. Higher rates of weaning failure and delayed
      extubation (≥ 48h) lead to ventilator associated pneumonia, higher mortality and necessity of
      tracheostomy.

      Therefore, improving the weaning of stroke patients from mechanical ventilation is warranted
      to prevent ventilator-associated complications and eventually improve clinical outcomes.

      This single-center, randomized, clinical trial aims at demonstrating that voices of patients'
      relatives support weaning from mechanical ventilation and reduce weaning failure in
      brain-injured patients.
Methods: Adult ICU-patients with controlled mechanical ventilation ≥48h due to a neurological
      disease will be included in the intensive care unit. A predefined text - including
      information on the patient's condition and recurrent request to breath in and out - will be
      recorded as an audio file by one of the patient's relatives. Patients will be randomly
      assigned in a 1:1 ratio to the conventional treatment arm or the Voice-Weaning arm. In the
      conventional arm, audio recordings will be muted by an independent person resulting in a mute
      recording without audio signals.

      When conversion from controlled to assisted mechanical ventilation is intended according to
      standard treatment, audio recordings will be administered in repeat mode for 10 minutes and
      performed three times per day. If spontaneous breathing trials (SBT) are intended according
      to standard treatment, the audio recordings will be played during the SBT three times per
      day.

      Criteria for weaning not to be intended - according to Boles et al. (Weaning from mechanical
      ventilation. Eur Respir J. 2007) and adapted to neurological patients:

      Objective measurements:

        -  Unstable clinical condition

             -  Cardiovascular status (fC≥140/min, systolic BP <90mmHg or >180mmHg, more than
                minimal vasopressors)

             -  Metabolic status (e.g. inacceptable electrolytes)

        -  Inadequate oxygenation

             -  SaO2 ≤90% on FiO2 >40% or pO2/FiO2 <150mmHg or pO2/FiO2 <120mmHg in case of chronic
                hypoxemia (Horowitz index)

             -  PEEP>8cmH2O

        -  Inadequate pulmonary function

             -  fR ≥35/min

             -  MIP>(-20 -) -25cmH2O

             -  VT ≤5ml/kgKG

             -  VC ≤10ml/kgKG

             -  fR/VT ≥105 breaths/min x l (RSBI)

             -  significant respiratory acidosis (pH≤7.25)

        -  Unstable neurological condition

             -  sedation or inadequate mentation on sedation

             -  present or anticipated intracranial mass effect (e.g. midline shift >10mm or
                progression, basal cistern effacement or oculomotor disturbance, signs of
                transfalxial/transtentorial/transforaminal herniation

             -  elevation of intracranial pressure (>20 cmH2O) and/or obstructive hydrocephalus

             -  severe vasospasms (>6 kHz in transcranial Doppler, or determined by CT-A/CT-P)

             -  status epilepticus (determined by EEG)

             -  acute intracranial infection (without established and/or treated origin)

      Clinical assessment:

        -  Inadequate cough

        -  Excessive tracheobronchial secretion

        -  Disease acute phase for which the patient was intubated

      Ethics Approval: The Institutional Review Board of the Friedrich-Alexander-Universität
      Erlangen-Nürnberg approved of the study on 13 November 2018.

      Sample Size Calculation: The sample size is computed with 80% power and a 5% α-risk for the
      hypothesis of Voice Weaning achieving a 15% absolute weaning failure reduction. The sample
      size is increased by 10% to correct for dropouts and lost to follow up: a maximum of 354
      patients will be included and an interim analysis be performed after inclusion of 50% of the
      calculated subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
measure: Rate of weaning failure
time frame: first 28 days after start of ventilation, or until 48 hours after extubation, or discharge from intensive care, whichever came first
description: Reintubation and/or resumption of ventilatory support following extubation or death following extubation or failed spontaneous breathing trial
measure: Time of controlled ventilation
time frame: first 28 days after start of ventilation or discharge from intensive care, whichever came first
measure: Rate of tracheotomy
time frame: first 28 days after start of ventilation or discharge from intensive care, whichever came first
description: Proportion of patients requiring tracheotomy performed as percutaneous dilatative tracheotomy or surgical tracheotomy
measure: All cause mortality rate at 90 days
time frame: first 90 days after start of ventilation
measure: Rate of ICU delirium
time frame: first 28 days after start of ventilation or discharge from intensive care, whichever came first
description: Development of delirium according to the Confusion Assessment Method for intensive care unit (CAM-ICU)
arm group label: Conventional arm
arm group type: Sham Comparator
description: Muted audio recordings of the patients relatives.
arm group label: Voice-Weaning arm
arm group type: Experimental
description: Audio recordings of the patients relatives including information on the patient's condition and recurrent request to breath in and out.
intervention type: Other
intervention name: Voice-Weaning
description: Audio recordings of patients' relatives for 10 minutes x 3 daily from initiation of assisted mechanical ventilation to extubation or ICU discharge.
arm group label: Voice-Weaning arm
intervention type: Other
intervention name: Sham control
description: Muted audio recordings of patients' relatives for 10 minutes x 3 daily from initiation of assisted mechanical ventilation to extubation or ICU discharge.
arm group label: Conventional arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hagen B. Huttner, MD, PhD
role: Principal Investigator
affiliation: University of Erlangen-Nürnberg Medical School, Department of Neurology, Germany
last name: Joji B. Kuramatsu, MD
role: Principal Investigator
affiliation: University of Erlangen-Nürnberg Medical School, Department of Neurology, Germany
last name: Maximilian I. Sprügel, MD
role: Principal Investigator
affiliation: University of Erlangen-Nürnberg Medical School, Department of Neurology, Germany
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Erlangen-Nürnberg Medical School
investigator full name: Hagen B. Huttner
investigator title: Principal Investigator
mesh term: Brain Injuries
sharing ipd: Undecided
ipd description: Because of local ethics committees restrictions the final decision upon release of the raw data has not been made.