<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/NCT04445649</url>
  </required_header>
  <id_info>
    <org_study_id>DOC-OUT</org_study_id>
    <nct_id>NCT04445649</nct_id>
  </id_info>
  <brief_title>Prognostic Factors to Regain Consciousness</brief_title>
  <official_title>Investigation of Prognostic Factors to Regain Consciousness in Neurological Early Rehabilitation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BDH-Klinik Hessisch Oldendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BDH-Klinik Hessisch Oldendorf</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 study aims to identify factors that predict the medium and long-term outcome of patients&#xD;
      with disorders of consciousness (DOC) undergoing early neurological rehabilitation.&#xD;
&#xD;
      In this prospective, observational study, 130 DOC patients are going to be included (36&#xD;
      months). At study entry, different routine data, disease severity and functional status are&#xD;
      documented for each patient. In addition, MRI, EEG and evoked potentials are measured within&#xD;
      the first week. The level of consciousness is recorded with the Coma-Recovery-Scale-Revised&#xD;
      and serves as the primary outcome parameter. Complications, comorbidities, functional status&#xD;
      and leve of consciousness are assessed weekly. After eight weeks, the measurement of the MRI,&#xD;
      the EEG and the evoked potentials are repeated. After 3, 6 and 12 months, the Glasgow Outcome&#xD;
      Scale-Revised is used to followed up the current status of the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to continuous improvements in acute medical care, the number of patients surviving severe&#xD;
      brain damage has increased over the past decades. While some patients improve significantly&#xD;
      during the first days after the injury, other patients remain in altered states of&#xD;
      consciousness (i.e. coma, unresponsive wakefulness syndrome or minimally conscious state).&#xD;
      Acquired brain damage such as cerebrovascular diseases, traumatic brain injuries or&#xD;
      hypoxic-ischemic encephalopathies are the main causes of severe impaired consciousness.The&#xD;
      correct classification of the level of consciousness is of great importance, since the&#xD;
      different states of consciousness are associated with different prognoses and treatment&#xD;
      options. Patients who show minimal signs of consciousness (MCS) a month after the onset of&#xD;
      the disease have better chances of regaining consciousness within one year than UWS patients.&#xD;
      Within both categories (UWS, MCS), traumatic aetiologies in turn have a better prognosis than&#xD;
      non-traumatic aetiologies. The prognosis usually begins with the admission of the patients to&#xD;
      the intensive care unit of the acute care facility. But even in later treatment phases, a&#xD;
      large number of patients regain consciousness, e.g. during post-acute early rehabilitation&#xD;
      and even years after the disease. Numerous factors are associated with the prognosis (e.g.&#xD;
      age, aetiology, duration of illness, functional status and state of consciousness). Although&#xD;
      there are numerous studies on the prognostic factors and outcome of patients with severe&#xD;
      brain damage, only a few have explicitly examined patients with initially severe and&#xD;
      long-lasting impaired consciousness. The study therefore aims to identify factors that&#xD;
      predict the medium and long-term outcome of patients with severe impaired consciousness in&#xD;
      early neurological rehabilitation.&#xD;
&#xD;
      Over a period of 36 months, 130 patients undergoing neurological early rehabilitation with&#xD;
      impaired consciousness are included. It is a prospective observational study that is carried&#xD;
      out in a single neurological rehabilitation centre (monocentric). Different routine data,&#xD;
      disease severity and functional status are documented for each patient. In addition, MRI, EEG&#xD;
      and evoked potentials are measured within the first week. The level of consciousness is&#xD;
      recorded with the Coma-Recovery-Scale-Revised and serves as the primary outcome parameter.&#xD;
      Complications, comorbidities, functional status and leve of consciousness are assessed&#xD;
      weekly. After eight weeks, the measurement of the MRI, the EEG and the evoked potentials are&#xD;
      repeated. After 3, 6 and 12 months, the Glasgow Outcome Scale-Revised is used to follow up&#xD;
      the current status of the patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 15, 2025</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>Changed functional status</measure>
    <time_frame>8 weeks</time_frame>
    <description>Functional status is measured with Early Rehabilitation Barthel Index (ERBI; Range: -325 to 100; higher scores mean a better outcome) weekly.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changed level of consciousness</measure>
    <time_frame>8 weeks</time_frame>
    <description>Level of consciousness is measured with the Coma-Recovery-Scale-Revised (CRS-R; Range: 0 to 23; higher scores mean a better outcome) weekly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration until consciousness is regained</measure>
    <time_frame>up to 8 weeks</time_frame>
    <description>Time until patients show first signs of consciousness</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Neurologic Disorder</condition>
  <condition>Disorder of Consciousness</condition>
  <condition>Traumatic Brain Injury</condition>
  <condition>Stroke</condition>
  <condition>Hypoxic-Ischemic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>ICU patients</arm_group_label>
    <description>Patients with impaired consciousness admitted to intensive care unit after severe brain injury</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Coma-Recovery-Scale-Revised (CRS-R)</intervention_name>
    <description>CRS-R assessments (15 minutes) are repeated weekly after study entry</description>
    <arm_group_label>ICU patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing neurological early rehabilitation with impaired consciousness and&#xD;
        admitted to intensive care unit&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  early neurological rehabilitation (phase B)&#xD;
&#xD;
          -  stroke, traumatic brain injury, hypoxic-ischemic encephalopathy&#xD;
&#xD;
          -  disorder of consciousness (coma, UWS, MCS)&#xD;
&#xD;
          -  at minimum two weeks after disease onset&#xD;
&#xD;
          -  admission to intensive care unit&#xD;
&#xD;
          -  written consent from the patient's legal representative&#xD;
&#xD;
          -  exclusion of pregnancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  insufficient cardiorespiratory stability&#xD;
&#xD;
          -  fractures or severe infratentorial brain injuries leading to impaired auditory evoked&#xD;
             - potentials&#xD;
&#xD;
          -  previous brain damage&#xD;
&#xD;
          -  mental disorders (dementia, depression)&#xD;
&#xD;
          -  colonization with multi-resistant pathogens&#xD;
&#xD;
          -  MRI contraindications&#xD;
&#xD;
          -  claustrophobia&#xD;
&#xD;
          -  weight &gt; 120 kg&#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>Jens D Rollnik, MD</last_name>
    <role>Study Director</role>
    <affiliation>BDH-Clinic Hessisch Oldendorf</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melanie Boltzmann, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BDH-Clinic Hessisch Oldendorf</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melanie Boltzmann, PhD</last_name>
    <phone>0049 5152 781 256</phone>
    <email>m.boltzmann@bdh-klinik-hessisch.oldendorf</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Simone B Schmidt, PhD</last_name>
    <phone>0049 5152 781 215</phone>
    <email>si.schmidt@bdh-klinik-hessisch.oldendorf</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BDH-Clinic Hessisch Oldendorf</name>
      <address>
        <city>Hessisch Oldendorf</city>
        <zip>31840</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melanie Boltzmann, PhD</last_name>
      <phone>0049 5152 781 256</phone>
      <email>m.boltzmann@bdh-klinik-hessisch-oldendorf.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Lucca LF, Lofaro D, Pignolo L, Leto E, Ursino M, Cortese MD, Conforti D, Tonin P, Cerasa A. Outcome prediction in disorders of consciousness: the role of coma recovery scale revised. BMC Neurol. 2019 Apr 18;19(1):68. doi: 10.1186/s12883-019-1293-7.</citation>
    <PMID>30999877</PMID>
  </reference>
  <reference>
    <citation>Portaccio E, Morrocchesi A, Romoli AM, Hakiki B, Taglioli MP, Lippi E, Di Renzone M, Grippo A, Macchi C; Intensive Rehabilitation Unit Study Group of the IRCCS Don Gnocchi Foundation, Italy. Improvement on the Coma Recovery Scale-Revised During the First Four Weeks of Hospital Stay Predicts Outcome at Discharge in Intensive Rehabilitation After Severe Brain Injury. Arch Phys Med Rehabil. 2018 May;99(5):914-919. doi: 10.1016/j.apmr.2018.01.015. Epub 2018 Feb 8.</citation>
    <PMID>29428346</PMID>
  </reference>
  <reference>
    <citation>Portaccio E, Morrocchesi A, Romoli AM, Hakiki B, Taglioli MP, Lippi E, Di Renzone M, Grippo A, Macchi C. Score on Coma Recovery Scale-Revised at admission predicts outcome at discharge in intensive rehabilitation after severe brain injury. Brain Inj. 2018;32(6):730-734. doi: 10.1080/02699052.2018.1440420. Epub 2018 Feb 26.</citation>
    <PMID>29482376</PMID>
  </reference>
  <reference>
    <citation>Estraneo A, Moretta P, Loreto V, Lanzillo B, Cozzolino A, Saltalamacchia A, Lullo F, Santoro L, Trojano L. Predictors of recovery of responsiveness in prolonged anoxic vegetative state. Neurology. 2013 Jan 29;80(5):464-70. doi: 10.1212/WNL.0b013e31827f0f31. Epub 2013 Jan 9.</citation>
    <PMID>23303855</PMID>
  </reference>
  <reference>
    <citation>Estraneo A, Moretta P, Loreto V, Lanzillo B, Santoro L, Trojano L. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology. 2010 Jul 20;75(3):239-45. doi: 10.1212/WNL.0b013e3181e8e8cc. Epub 2010 Jun 16.</citation>
    <PMID>20554941</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neurological rehabilitation</keyword>
  <keyword>Prognosis</keyword>
  <keyword>Outcome</keyword>
  <keyword>Level of consciousness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Hypoxia-Ischemia, Brain</mesh_term>
    <mesh_term>Consciousness Disorders</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD that underlie results in a publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Period of availability begins when results are published, at the earliest in Dec 2023</ipd_time_frame>
    <ipd_access_criteria>IPD can be obtained from the principal investigator upon reasonable request.</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/NCT04445649
org study id: DOC-OUT
nct id: NCT04445649
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study aims to identify factors that predict the medium and long-term outcome of patients
      with disorders of consciousness (DOC) undergoing early neurological rehabilitation.

      In this prospective, observational study, 130 DOC patients are going to be included (36
      months). At study entry, different routine data, disease severity and functional status are
      documented for each patient. In addition, MRI, EEG and evoked potentials are measured within
      the first week. The level of consciousness is recorded with the Coma-Recovery-Scale-Revised
      and serves as the primary outcome parameter. Complications, comorbidities, functional status
      and leve of consciousness are assessed weekly. After eight weeks, the measurement of the MRI,
      the EEG and the evoked potentials are repeated. After 3, 6 and 12 months, the Glasgow Outcome
      Scale-Revised is used to followed up the current status of the patients.
Due to continuous improvements in acute medical care, the number of patients surviving severe
      brain damage has increased over the past decades. While some patients improve significantly
      during the first days after the injury, other patients remain in altered states of
      consciousness (i.e. coma, unresponsive wakefulness syndrome or minimally conscious state).
      Acquired brain damage such as cerebrovascular diseases, traumatic brain injuries or
      hypoxic-ischemic encephalopathies are the main causes of severe impaired consciousness.The
      correct classification of the level of consciousness is of great importance, since the
      different states of consciousness are associated with different prognoses and treatment
      options. Patients who show minimal signs of consciousness (MCS) a month after the onset of
      the disease have better chances of regaining consciousness within one year than UWS patients.
      Within both categories (UWS, MCS), traumatic aetiologies in turn have a better prognosis than
      non-traumatic aetiologies. The prognosis usually begins with the admission of the patients to
      the intensive care unit of the acute care facility. But even in later treatment phases, a
      large number of patients regain consciousness, e.g. during post-acute early rehabilitation
      and even years after the disease. Numerous factors are associated with the prognosis (e.g.
      age, aetiology, duration of illness, functional status and state of consciousness). Although
      there are numerous studies on the prognostic factors and outcome of patients with severe
      brain damage, only a few have explicitly examined patients with initially severe and
      long-lasting impaired consciousness. The study therefore aims to identify factors that
      predict the medium and long-term outcome of patients with severe impaired consciousness in
      early neurological rehabilitation.

      Over a period of 36 months, 130 patients undergoing neurological early rehabilitation with
      impaired consciousness are included. It is a prospective observational study that is carried
      out in a single neurological rehabilitation centre (monocentric). Different routine data,
      disease severity and functional status are documented for each patient. In addition, MRI, EEG
      and evoked potentials are measured within the first week. The level of consciousness is
      recorded with the Coma-Recovery-Scale-Revised and serves as the primary outcome parameter.
      Complications, comorbidities, functional status and leve of consciousness are assessed
      weekly. After eight weeks, the measurement of the MRI, the EEG and the evoked potentials are
      repeated. After 3, 6 and 12 months, the Glasgow Outcome Scale-Revised is used to follow up
      the current status of the patients.
observational model: Cohort
time perspective: Prospective
measure: Changed functional status
time frame: 8 weeks
description: Functional status is measured with Early Rehabilitation Barthel Index (ERBI; Range: -325 to 100; higher scores mean a better outcome) weekly.
measure: Changed level of consciousness
time frame: 8 weeks
description: Level of consciousness is measured with the Coma-Recovery-Scale-Revised (CRS-R; Range: 0 to 23; higher scores mean a better outcome) weekly.
measure: Duration until consciousness is regained
time frame: up to 8 weeks
description: Time until patients show first signs of consciousness
arm group label: ICU patients
description: Patients with impaired consciousness admitted to intensive care unit after severe brain injury
intervention type: Diagnostic Test
intervention name: Coma-Recovery-Scale-Revised (CRS-R)
description: CRS-R assessments (15 minutes) are repeated weekly after study entry
arm group label: ICU patients
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jens D Rollnik, MD
role: Study Director
affiliation: BDH-Clinic Hessisch Oldendorf
last name: Melanie Boltzmann, PhD
role: Principal Investigator
affiliation: BDH-Clinic Hessisch Oldendorf
last name: Melanie Boltzmann, PhD
phone: 0049 5152 781 256
email: m.boltzmann@bdh-klinik-hessisch.oldendorf
last name: Simone B Schmidt, PhD
phone: 0049 5152 781 215
email: si.schmidt@bdh-klinik-hessisch.oldendorf
facility: 
status: Recruiting
contact: 
country: Germany
citation: Lucca LF, Lofaro D, Pignolo L, Leto E, Ursino M, Cortese MD, Conforti D, Tonin P, Cerasa A. Outcome prediction in disorders of consciousness: the role of coma recovery scale revised. BMC Neurol. 2019 Apr 18;19(1):68. doi: 10.1186/s12883-019-1293-7.
PMID: 30999877
citation: Portaccio E, Morrocchesi A, Romoli AM, Hakiki B, Taglioli MP, Lippi E, Di Renzone M, Grippo A, Macchi C; Intensive Rehabilitation Unit Study Group of the IRCCS Don Gnocchi Foundation, Italy. Improvement on the Coma Recovery Scale-Revised During the First Four Weeks of Hospital Stay Predicts Outcome at Discharge in Intensive Rehabilitation After Severe Brain Injury. Arch Phys Med Rehabil. 2018 May;99(5):914-919. doi: 10.1016/j.apmr.2018.01.015. Epub 2018 Feb 8.
PMID: 29428346
citation: Portaccio E, Morrocchesi A, Romoli AM, Hakiki B, Taglioli MP, Lippi E, Di Renzone M, Grippo A, Macchi C. Score on Coma Recovery Scale-Revised at admission predicts outcome at discharge in intensive rehabilitation after severe brain injury. Brain Inj. 2018;32(6):730-734. doi: 10.1080/02699052.2018.1440420. Epub 2018 Feb 26.
PMID: 29482376
citation: Estraneo A, Moretta P, Loreto V, Lanzillo B, Cozzolino A, Saltalamacchia A, Lullo F, Santoro L, Trojano L. Predictors of recovery of responsiveness in prolonged anoxic vegetative state. Neurology. 2013 Jan 29;80(5):464-70. doi: 10.1212/WNL.0b013e31827f0f31. Epub 2013 Jan 9.
PMID: 23303855
citation: Estraneo A, Moretta P, Loreto V, Lanzillo B, Santoro L, Trojano L. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology. 2010 Jul 20;75(3):239-45. doi: 10.1212/WNL.0b013e3181e8e8cc. Epub 2010 Jun 16.
PMID: 20554941
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Brain Diseases
mesh term: Brain Ischemia
mesh term: Hypoxia-Ischemia, Brain
mesh term: Consciousness Disorders
mesh term: Nervous System Diseases
sharing ipd: Yes
ipd description: All IPD that underlie results in a publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Period of availability begins when results are published, at the earliest in Dec 2023
ipd access criteria: IPD can be obtained from the principal investigator upon reasonable request.