<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/NCT03300479</url>
  </required_header>
  <id_info>
    <org_study_id>2017-00379</org_study_id>
    <nct_id>NCT03300479</nct_id>
  </id_info>
  <brief_title>Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®)</brief_title>
  <acronym>Clevidipine</acronym>
  <official_title>Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®) for Blood Pressure Reduction in Patients With Primary Intracerebral Hemorrhage: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</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>
      Intracerebral hemorrhage (ICH) is responsible for 10-15% of primary strokes. ICH is a dynamic&#xD;
      process with three phases: initial hemorrhage, followed by hematoma expansion and&#xD;
      perihematoma edema formation. Hematoma volume is correlated with disease progression and&#xD;
      outcome. Contemporary evidence proposes that elevated blood pressure is associated with&#xD;
      hematoma expansion while more than 90% of patients with ICH present with acute hypertension.&#xD;
      Uncontrolled blood pressure is a leading cause of ICH and it seems also to be a factor of&#xD;
      poorer outcomes. Therefore, rapid reduction and control of blood pressure might ease disease&#xD;
      progression and improve the outcome. Clevidipine (Cleviprex®), an ultrashort-acting&#xD;
      dihydropyridine calcium channel antagonist, with its rapid onset and short duration might be&#xD;
      more effective than conventional antihypertensives to achieve rapid blood pressure control in&#xD;
      patients with acute ICH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After admission to the ICU the patients presenting with primary intracerebral hemorrhage&#xD;
      (ICH) are evaluated for enrollment. If systolic blood pressure (SBP) is higher than 160 mmHg&#xD;
      or SBP &lt;160 mmHg under intravenous antihypertensive drug (e.g. Urapidil), started less than 3&#xD;
      h before randomization, the patient will be randomized in one of the two study groups and&#xD;
      intravenous therapy with Clevidipine (Cleviprex®) or Urapidil (Ebrantil®) will start&#xD;
      immediately. Data of systemic haemodynamics will be collected continuously by online&#xD;
      monitoring, starting at baseline and ending after 24h (study data measurements). In&#xD;
      particular, all blood pressure measurements are extracted via an arterial line, which is&#xD;
      placed as standard of care in these patients. If the target values are not attained within 30&#xD;
      minutes, the investigators can add or switch to alternative antihypertensive drugs of their&#xD;
      choice. 24h after initiation of Clevidipine (Cleviprex®) or Urapidil (Ebrantil®), all&#xD;
      patients receive Nicardipine (Cardene®) (standard care in daily clinical routine) for another&#xD;
      24h followed by orally administered antihypertensive medication.&#xD;
&#xD;
      Intracerebral hematoma volume will be determined by readings of noncontrast brain computed&#xD;
      tomography (CT) scans using the ABC/2 rule to calculate the volume. As a standard in these&#xD;
      patients a CT scan is performed 6 hours after admission to the ICU.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No patient enrolled. No study conduct due to lack of human resources.&#xD;
  </why_stopped>
  <start_date type="Actual">June 15, 2017</start_date>
  <completion_date type="Actual">May 14, 2021</completion_date>
  <primary_completion_date type="Actual">May 14, 2021</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>After admission to the ICU the patients presenting with primary intracerebral hemorrhage are evaluated for enrollment. If systolic blood pressure is higher than 160 mmHg or &lt;160 mmHg under intravenous antihypertensive drug, started less than 3 h before randomizsation, the patient will be randomized in one of the two study groups and intravenous therapy with Cleviprex® or Ebrantil® will start immediately. Data of systemic haemodynamics will be collected continuously by online monitoring, starting at baseline and ending after 24h. If the target values are not attained within 30 minutes, the investigators can add or switch to alternative antihypertensive drugs of their choice. 24h after initiation of Cleviprex® or Ebrantil®, all patients receive Cardene® (standard care in daily clinical routine) for another 24h followed by orally administered antihypertensive medication.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Achieving the target systolic blood pressure</measure>
    <time_frame>1/2 hours</time_frame>
    <description>Number of patients achieving the target systolic blood pressure (SBP) values (160 -120 mmHg) within 30 minutes after initiation of Clevidipine (Cleviprex®) or Urapidil (Ebrantil®)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hypertensive burden - time</measure>
    <time_frame>24 hours</time_frame>
    <description>• Hypertensive burden - time out of target range (SBP &gt; 160 mmHg) multiplied with the numeric difference to 160mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypotensive burden - time</measure>
    <time_frame>24 hours</time_frame>
    <description>• Hypotensive burden - time out of target range (SBP &lt; 120 mmHg) multiplied with the numeric difference to 120mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative time out</measure>
    <time_frame>24 hours</time_frame>
    <description>• Cumulative time out of target systolic blood pressure range (&gt;160 or &lt;120 mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure variability</measure>
    <time_frame>48 hours</time_frame>
    <description>• Blood pressure variability (determined as Standard Deviation (SD) of SBP over time)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematoma growth</measure>
    <time_frame>6 hours</time_frame>
    <description>• Hematoma growth within 6 hours after admission (CCT scan)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological state 1</measure>
    <time_frame>48 hours</time_frame>
    <description>• Glasgow Coma Scale (GCS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological state 2</measure>
    <time_frame>48 hours</time_frame>
    <description>• modified Ranking Scale (mRS)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Costs</measure>
    <time_frame>24 hours</time_frame>
    <description>• Cost of study drugs</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Nontraumatic Intracerebral Hemorrhage, Multiple Localized</condition>
  <arm_group>
    <arm_group_label>Clevidipine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The treatment starts at admission to the ICU for 24 hours with 2 mg to a maximum of 16 mg Clevidipine per hour infused intravenously and continuously to reach the systolic target pressure &lt; 160 mmHg (&gt;120 mmHg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Urapidil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The treatment starts at admission to the ICU for 24 hours with 5 mg to a maximum of 40 mg Urapidil per hour infused intravenously and continuously to reach the systolic target pressure &lt; 160 mmHg (&gt;120 mmHg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clevidipine</intervention_name>
    <description>Intravenous antihypertensive therapy with Clevidipine for the first 24 hours in patients with nontraumatic intracerebral hemorrhage (ICH).</description>
    <arm_group_label>Clevidipine</arm_group_label>
    <other_name>Cleviprex®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Urapidil</intervention_name>
    <description>We compare the therapy with Urapidil to Clevidipine for the acute phase (24 hours) in patients with ICH. We would like to show the efficacy and safety of Clevidipine in this special situation.</description>
    <arm_group_label>Urapidil</arm_group_label>
    <other_name>Ebrantil®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary intracerebral hemorrhage (ICH)&#xD;
&#xD;
          -  Systolic blood pressure (SBP) &gt; 160 mmHg at screening&#xD;
&#xD;
          -  Systolic blood pressure (SBP) &lt;160 mmHg under intravenous antihypertensive drug (e.g.&#xD;
             Urapidil), started less than 3 h before randomization&#xD;
&#xD;
          -  18 to unlimited years of age&#xD;
&#xD;
          -  Signed informed consent obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with secondary hemorrhage (bleeding source as aneurysm, arteriovenous&#xD;
             malformation or traumatic)&#xD;
&#xD;
          -  Patients with concomitant severe critical illness (e.g. sepsis, multi-organ failure)&#xD;
&#xD;
          -  Positive pregnancy test for any female of childbearing potential or breast feeding&#xD;
             female&#xD;
&#xD;
          -  Known allergy to any component of Clevidipine (Cleviprex®), Urapidil Ebrantil®), soya&#xD;
             bean oil or severe egg protein allergy&#xD;
&#xD;
          -  Contraindications for Clevidipine (Cleviprex®): defect in the lipid metabolism,&#xD;
             critical aortic stenosis&#xD;
&#xD;
          -  Contraindications for Urapidil (Ebrantil®): aortic coarctation, arterio-venous shunt,&#xD;
             breastfeeding period&#xD;
&#xD;
          -  Patients with pre-existing disability and legal representative&#xD;
&#xD;
          -  Patients participating in a interventional clinical trial within the last 30 days&#xD;
             before Start of Treatment&#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>Emanuela Keller, MD Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Zurich</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Zurich</name>
      <address>
        <city>Zurich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>November 2, 2021</last_update_submitted>
  <last_update_submitted_qc>November 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Zurich</investigator_affiliation>
    <investigator_full_name>Emanuela Keller</investigator_full_name>
    <investigator_title>Prof. Dr. med.</investigator_title>
  </responsible_party>
  <keyword>nontraumatic intracerebral hemorrhage</keyword>
  <keyword>Cleviprex®</keyword>
  <keyword>Ebrantil®</keyword>
  <keyword>Systolic blood pressure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urapidil</mesh_term>
    <mesh_term>Clevidipine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03300479
org study id: 2017-00379
nct id: NCT03300479
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Intracerebral hemorrhage (ICH) is responsible for 10-15% of primary strokes. ICH is a dynamic
      process with three phases: initial hemorrhage, followed by hematoma expansion and
      perihematoma edema formation. Hematoma volume is correlated with disease progression and
      outcome. Contemporary evidence proposes that elevated blood pressure is associated with
      hematoma expansion while more than 90% of patients with ICH present with acute hypertension.
      Uncontrolled blood pressure is a leading cause of ICH and it seems also to be a factor of
      poorer outcomes. Therefore, rapid reduction and control of blood pressure might ease disease
      progression and improve the outcome. Clevidipine (Cleviprex®), an ultrashort-acting
      dihydropyridine calcium channel antagonist, with its rapid onset and short duration might be
      more effective than conventional antihypertensives to achieve rapid blood pressure control in
      patients with acute ICH.
After admission to the ICU the patients presenting with primary intracerebral hemorrhage
      (ICH) are evaluated for enrollment. If systolic blood pressure (SBP) is higher than 160 mmHg
      or SBP <160 mmHg under intravenous antihypertensive drug (e.g. Urapidil), started less than 3
      h before randomization, the patient will be randomized in one of the two study groups and
      intravenous therapy with Clevidipine (Cleviprex®) or Urapidil (Ebrantil®) will start
      immediately. Data of systemic haemodynamics will be collected continuously by online
      monitoring, starting at baseline and ending after 24h (study data measurements). In
      particular, all blood pressure measurements are extracted via an arterial line, which is
      placed as standard of care in these patients. If the target values are not attained within 30
      minutes, the investigators can add or switch to alternative antihypertensive drugs of their
      choice. 24h after initiation of Clevidipine (Cleviprex®) or Urapidil (Ebrantil®), all
      patients receive Nicardipine (Cardene®) (standard care in daily clinical routine) for another
      24h followed by orally administered antihypertensive medication.

      Intracerebral hematoma volume will be determined by readings of noncontrast brain computed
      tomography (CT) scans using the ABC/2 rule to calculate the volume. As a standard in these
      patients a CT scan is performed 6 hours after admission to the ICU.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: After admission to the ICU the patients presenting with primary intracerebral hemorrhage are evaluated for enrollment. If systolic blood pressure is higher than 160 mmHg or <160 mmHg under intravenous antihypertensive drug, started less than 3 h before randomizsation, the patient will be randomized in one of the two study groups and intravenous therapy with Cleviprex® or Ebrantil® will start immediately. Data of systemic haemodynamics will be collected continuously by online monitoring, starting at baseline and ending after 24h. If the target values are not attained within 30 minutes, the investigators can add or switch to alternative antihypertensive drugs of their choice. 24h after initiation of Cleviprex® or Ebrantil®, all patients receive Cardene® (standard care in daily clinical routine) for another 24h followed by orally administered antihypertensive medication.
primary purpose: Treatment
masking: None (Open Label)
measure: Achieving the target systolic blood pressure
time frame: 1/2 hours
description: Number of patients achieving the target systolic blood pressure (SBP) values (160 -120 mmHg) within 30 minutes after initiation of Clevidipine (Cleviprex®) or Urapidil (Ebrantil®)
measure: Hypertensive burden - time
time frame: 24 hours
description: • Hypertensive burden - time out of target range (SBP > 160 mmHg) multiplied with the numeric difference to 160mmHg
measure: Hypotensive burden - time
time frame: 24 hours
description: • Hypotensive burden - time out of target range (SBP < 120 mmHg) multiplied with the numeric difference to 120mmHg
measure: Cumulative time out
time frame: 24 hours
description: • Cumulative time out of target systolic blood pressure range (>160 or <120 mmHg)
measure: Blood pressure variability
time frame: 48 hours
description: • Blood pressure variability (determined as Standard Deviation (SD) of SBP over time)
measure: Hematoma growth
time frame: 6 hours
description: • Hematoma growth within 6 hours after admission (CCT scan)
measure: Neurological state 1
time frame: 48 hours
description: • Glasgow Coma Scale (GCS)
measure: Neurological state 2
time frame: 48 hours
description: • modified Ranking Scale (mRS)
measure: Costs
time frame: 24 hours
description: • Cost of study drugs
arm group label: Clevidipine
arm group type: Experimental
description: The treatment starts at admission to the ICU for 24 hours with 2 mg to a maximum of 16 mg Clevidipine per hour infused intravenously and continuously to reach the systolic target pressure < 160 mmHg (>120 mmHg).
arm group label: Urapidil
arm group type: Active Comparator
description: The treatment starts at admission to the ICU for 24 hours with 5 mg to a maximum of 40 mg Urapidil per hour infused intravenously and continuously to reach the systolic target pressure < 160 mmHg (>120 mmHg).
intervention type: Drug
intervention name: Clevidipine
description: Intravenous antihypertensive therapy with Clevidipine for the first 24 hours in patients with nontraumatic intracerebral hemorrhage (ICH).
arm group label: Clevidipine
other name: Cleviprex®
intervention type: Drug
intervention name: Urapidil
description: We compare the therapy with Urapidil to Clevidipine for the acute phase (24 hours) in patients with ICH. We would like to show the efficacy and safety of Clevidipine in this special situation.
arm group label: Urapidil
other name: Ebrantil®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emanuela Keller, MD Prof
role: Principal Investigator
affiliation: University of Zurich
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University of Zurich
investigator full name: Emanuela Keller
investigator title: Prof. Dr. med.
mesh term: Cerebral Hemorrhage
mesh term: Hemorrhage
mesh term: Urapidil
mesh term: Clevidipine
sharing ipd: No