<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/NCT02248441</url>
  </required_header>
  <id_info>
    <org_study_id>VEK: 1-10-72-173-14</org_study_id>
    <nct_id>NCT02248441</nct_id>
  </id_info>
  <brief_title>Effect of Remote Ischemic Conditioning in Patients With Chronic Ischemic Heart Failure</brief_title>
  <acronym>CONDI-HF</acronym>
  <official_title>Effect of Remote Ischemic Conditioning in Patients With Chronic Ischemic Heart Failure (CONDI-HF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aarhus University Hospital Skejby</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Central Jutland Regional Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study will evaluate whether treatment with daily remote ischemic conditioning for&#xD;
      a 28±4-day period induces beneficial effects in subjects with and without chronic ischemic&#xD;
      heart failure in terms of improved left ventricular contractile function and exercise&#xD;
      capacity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background Chronic heart failure (CHF) is a leading cause of morbidity and mortality&#xD;
      throughout the world, and the incidence and prevalence are increasing as more patients&#xD;
      survive their acute coronary syndrome. The disease is caused by abnormalities in cardiac&#xD;
      structure or function leading to insufficient delivery of oxygen to the metabolizing tissues.&#xD;
      These patients are often debilitated, require chronic medications, and many receive expensive&#xD;
      device therapy to manage symptoms. Consequently, this has led to an increasing economic and&#xD;
      health burden from heart failure.&#xD;
&#xD;
      CHF is the end-stage of a broad range of underlying cardiovascular diseases, but is most&#xD;
      frequently caused by ischemic heart disease. Other contributory causes include hypertension,&#xD;
      heart valve diseases, arrhythmias and cardiomyopathies, all resulting in myocardial tissue&#xD;
      damage and loss of ventricular function. Activation of neurohormonal and inflammatory&#xD;
      compensatory mechanisms lead to a vicious circle through adaptive metabolic and remodeling&#xD;
      processes, eventually resulting in a progressive decline of cardiac function with significant&#xD;
      morbidity and mortality.&#xD;
&#xD;
      Identification of the specific underlying cardiac condition is crucial for the therapeutic&#xD;
      approach in patients suffering from CHF. While pharmacological treatment remains dominating,&#xD;
      resynchronization therapy and surgical resection of non-contractile tissue are also&#xD;
      increasingly being conducted. Despite the fact that activation of the inflammatory system&#xD;
      greatly contributes to the remodeling process through initiation of myocardial fibrosis and&#xD;
      hypertrophy, most clinical studies targeting inflammatory components have been discouraging.&#xD;
&#xD;
      Remote ischemic conditioning (RIC) by brief non-lethal episodes of ischemia in a remote organ&#xD;
      or tissue (e.g. a limb) is a novel therapeutic method to achieve protection against&#xD;
      ischemia-reperfusion injury in the target organ, e.g. the heart . In the clinical setting,&#xD;
      RIC is most often performed by repeated episodes of limb ischemia achieved by intermittent&#xD;
      inflation of a blood pressure cuff placed around the upper arm. In clinical randomized&#xD;
      trials, RIC has been shown to reduce the amount of myocardial injury and improve long-term&#xD;
      outcome in patients admitted with STEMI for primary percutaneous coronary intervention and&#xD;
      patients undergoing cardiac surgery or elective coronary intervention.&#xD;
&#xD;
      RIC is a low-cost, simple and safe procedure that can easily be conducted using a standard&#xD;
      blood pressure cuff, and the method is increasingly used in clinical trials. The mechanisms&#xD;
      behind RIC are not yet fully understood, but the cardioprotective effects are believed to be&#xD;
      caused by neural and humoral signaling cascades as well as systemic anti-inflammatory effects&#xD;
      resulting in a cytoprotective state. In addition, RIC has been shown to reduce thrombus&#xD;
      formation. Since activation of platelets and the coagulation system are fundamental in&#xD;
      thrombus formation and degradation, another possible mechanism of the described effects of&#xD;
      RIC could be a result from effect on arterial thrombus formation.&#xD;
&#xD;
      The vast majority of experimental and clinical studies have utilized RIC as single-occasion&#xD;
      treatment (i.e. 3 or 4 bouts of short limb ischemia conducted once). However, experimental&#xD;
      studies have recently suggested that repeated RIC treatment may infer further beneficial&#xD;
      effects. Repeated RIC application has been shown to improve endothelial function and modify&#xD;
      leukocyte adhesion in healthy volunteers. In a rat model of myocardial infarction, RIC&#xD;
      repeated daily for 28 days after infarction reduced adverse ventricular remodeling and&#xD;
      improved survival. Consequently, two on-going clinical trials (clinicaltrials.gov: DREAM&#xD;
      study NCT01664611 and CRIC-RCT study NCT01817114) are investigating the effect of repeated&#xD;
      RIC on LVEF function in patients with reduced ventricular function after an acute coronary&#xD;
      event. Another study investigates the effect of repeated RIC on patients with severe heart&#xD;
      failure and left ventricular assist device (IMPULSE study NCT02044471).&#xD;
&#xD;
      So far, the effect of RIC on patients suffering from stable chronic ischemic heart failure is&#xD;
      unknown. Furthermore, no registered studies have evaluated the effect of long-term RIC given&#xD;
      as additive treatment to the standard medical therapy in patients with chronic ischemic heart&#xD;
      failure.&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      • We hypothesize, that the combination of anti-remodelling and anti-inflammatory properties&#xD;
      together with improved endothelial function induced by repetitive RIC treatment translate&#xD;
      into improved left ventricular function and better physical performance in subjects with CHF.&#xD;
&#xD;
      Purpose&#xD;
&#xD;
        -  To determine whether RIC applied on a daily basis for 4 weeks improves left ventricular&#xD;
           function as assessed by cardiac magnetic resonance imaging (MRI) in subjects with CHF.&#xD;
&#xD;
        -  To investigate whether RIC applied on a daily basis for 4 weeks improves muscle&#xD;
           strength, cardiopulmonary exercise capacity and thrombocyte function, and changes blood&#xD;
           biomarker levels of inflammation and heart failure in subjects with CHF.&#xD;
&#xD;
        -  To investigate whether the above-mentioned measurements differ between patients with CHF&#xD;
           and matched subjects after RIC applied on a daily basis for 4 weeks.&#xD;
&#xD;
      Perspectives The present study will elucidate whether long-term RIC treatment induces&#xD;
      beneficial effects in subjects with and without chronic ischemic heart failure in terms of&#xD;
      improved left ventricular contractile function and exercise capacity, and whether long-term&#xD;
      RIC treatment induces systemic anti-inflammatory effects in these subjects. Moreover, we find&#xD;
      that the study can uncover some of the mechanisms behind RIC and thus potentially optimize&#xD;
      future treatment for patients suffering, or at risk, from ischemic heart diseases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>N/A</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>Left ventricular ejection fraction assessed by MRI</measure>
    <time_frame>28±4 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Global and regional myocardial function by strain analysis assessed by MRI</measure>
    <time_frame>28±4 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular mass and end-diastolic volume assessed by MRI</measure>
    <time_frame>28±4 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac output assessed by MRI</measure>
    <time_frame>28±4 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiopulmonary exercise capacity assessed by staged exercise bicycle test and leg extension power rig test</measure>
    <time_frame>28±4 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serology markers for heart failure</measure>
    <time_frame>28±4 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serology inflammatory markers</measure>
    <time_frame>28±4 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Chronic Systolic Heart Failure</condition>
  <arm_group>
    <arm_group_label>Daily RIC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily ischemic conditioning treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Daily ischemic conditioning treatment</intervention_name>
    <description>RIC stimulus will be conducted as 4 x 5 minutes upper arm ischemia achieved by inflation of a blood pressure cuff to 200 mmHg and 5 minutes reperfusion between inflations. The procedure will be performed using the AutoRICTM (CellAegis Devices Inc., Toronto, Ontario, Canada).</description>
    <arm_group_label>Daily RIC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Group 1 (Chronic heart failure patients):&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt;18 years of age&#xD;
&#xD;
          -  Able to understand the written patient information and to give informed consent&#xD;
&#xD;
          -  Chronic congestive ischemic heart failure&#xD;
&#xD;
          -  Left ventricular ejection fraction ≤45%&#xD;
&#xD;
          -  New York Heart Association functional class I-III&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recent cardiovascular hospitalization (within last 30 days) • Strenuous exercise&#xD;
             within 72 hours of either study visits&#xD;
&#xD;
          -  Intake of caffeine within 24 hours of either study visit&#xD;
&#xD;
          -  Intake of alcohol within 24 hours of either study visit&#xD;
&#xD;
          -  Patients with permanent atrial fibrillation • Patients with diabetes mellitus&#xD;
&#xD;
          -  Patients with peripheral neuropathy&#xD;
&#xD;
          -  Patients in dialysis treatment&#xD;
&#xD;
          -  Contraindication for Magnetic Resonance Imaging examination (e.g. metal implants&#xD;
             including Cardiac Resynchronisation Therapy devices and other pacemakers or&#xD;
             defibrillators) precluding Magnetic Resonance Imaging&#xD;
&#xD;
          -  Other concomitant disease or treatment that according to the investigator's assessment&#xD;
             makes the patient unsuitable for study participation.&#xD;
&#xD;
        Group 2 (Volunteers without ischemic heart disease):&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  &gt;18 years of age&#xD;
&#xD;
          -  Able to understand the written patient information and to give informed consent&#xD;
&#xD;
          -  Left ventricular ejection fraction &gt;45%&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Recent cardiovascular hospitalization (within last 30 days)&#xD;
&#xD;
          -  Intake of acetylsalicylic acid or non-steroidal anti-inflammatory drug medication&#xD;
             within 7 days of either study visit&#xD;
&#xD;
          -  Strenuous exercise within 72 hours of either study visit&#xD;
&#xD;
          -  Intake of caffeine within 24 hours of either study visit&#xD;
&#xD;
          -  Intake of alcohol within 24 hours of either study visit&#xD;
&#xD;
          -  Patients with ischemic heart disease&#xD;
&#xD;
          -  Patients with diabetes mellitus&#xD;
&#xD;
          -  Patients with peripheral neuropathy&#xD;
&#xD;
          -  Patients in dialysis treatment&#xD;
&#xD;
          -  Patients in treatment with Vitamin K-antagonists, adenosine&#xD;
             diphosphate-receptor-inhibitor, oral anticoagulants or dipyridamol.&#xD;
&#xD;
          -  Conditions contraindicating short term cessation of acetylsalicylic acid and/or&#xD;
             non-steroidal anti-inflammatory drug intake&#xD;
&#xD;
          -  Contraindication for Magnetic Resonance Imaging examination (e.g. metal implants)&#xD;
             precluding Magnetic Resonance Imaging&#xD;
&#xD;
          -  Other concomitant disease or treatment that according to the investigator's assessment&#xD;
             makes the patient unsuitable for study participation.&#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>Hans Erik Bøtker, Prof.</last_name>
    <role>Study Director</role>
    <affiliation>Department of Cardiology, Aarhus University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aarhus University Hospital Skejby</name>
      <address>
        <city>Aarhus N</city>
        <state>DK-8200 Aarhus N</state>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>August 23, 2017</last_update_submitted>
  <last_update_submitted_qc>August 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Heart Failure, Systolic</mesh_term>
  </condition_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/NCT02248441
org study id: VEK: 1-10-72-173-14
nct id: NCT02248441
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The present study will evaluate whether treatment with daily remote ischemic conditioning for
      a 28±4-day period induces beneficial effects in subjects with and without chronic ischemic
      heart failure in terms of improved left ventricular contractile function and exercise
      capacity.
Background Chronic heart failure (CHF) is a leading cause of morbidity and mortality
      throughout the world, and the incidence and prevalence are increasing as more patients
      survive their acute coronary syndrome. The disease is caused by abnormalities in cardiac
      structure or function leading to insufficient delivery of oxygen to the metabolizing tissues.
      These patients are often debilitated, require chronic medications, and many receive expensive
      device therapy to manage symptoms. Consequently, this has led to an increasing economic and
      health burden from heart failure.

      CHF is the end-stage of a broad range of underlying cardiovascular diseases, but is most
      frequently caused by ischemic heart disease. Other contributory causes include hypertension,
      heart valve diseases, arrhythmias and cardiomyopathies, all resulting in myocardial tissue
      damage and loss of ventricular function. Activation of neurohormonal and inflammatory
      compensatory mechanisms lead to a vicious circle through adaptive metabolic and remodeling
      processes, eventually resulting in a progressive decline of cardiac function with significant
      morbidity and mortality.

      Identification of the specific underlying cardiac condition is crucial for the therapeutic
      approach in patients suffering from CHF. While pharmacological treatment remains dominating,
      resynchronization therapy and surgical resection of non-contractile tissue are also
      increasingly being conducted. Despite the fact that activation of the inflammatory system
      greatly contributes to the remodeling process through initiation of myocardial fibrosis and
      hypertrophy, most clinical studies targeting inflammatory components have been discouraging.

      Remote ischemic conditioning (RIC) by brief non-lethal episodes of ischemia in a remote organ
      or tissue (e.g. a limb) is a novel therapeutic method to achieve protection against
      ischemia-reperfusion injury in the target organ, e.g. the heart . In the clinical setting,
      RIC is most often performed by repeated episodes of limb ischemia achieved by intermittent
      inflation of a blood pressure cuff placed around the upper arm. In clinical randomized
      trials, RIC has been shown to reduce the amount of myocardial injury and improve long-term
      outcome in patients admitted with STEMI for primary percutaneous coronary intervention and
      patients undergoing cardiac surgery or elective coronary intervention.

      RIC is a low-cost, simple and safe procedure that can easily be conducted using a standard
      blood pressure cuff, and the method is increasingly used in clinical trials. The mechanisms
      behind RIC are not yet fully understood, but the cardioprotective effects are believed to be
      caused by neural and humoral signaling cascades as well as systemic anti-inflammatory effects
      resulting in a cytoprotective state. In addition, RIC has been shown to reduce thrombus
      formation. Since activation of platelets and the coagulation system are fundamental in
      thrombus formation and degradation, another possible mechanism of the described effects of
      RIC could be a result from effect on arterial thrombus formation.

      The vast majority of experimental and clinical studies have utilized RIC as single-occasion
      treatment (i.e. 3 or 4 bouts of short limb ischemia conducted once). However, experimental
      studies have recently suggested that repeated RIC treatment may infer further beneficial
      effects. Repeated RIC application has been shown to improve endothelial function and modify
      leukocyte adhesion in healthy volunteers. In a rat model of myocardial infarction, RIC
      repeated daily for 28 days after infarction reduced adverse ventricular remodeling and
      improved survival. Consequently, two on-going clinical trials (clinicaltrials.gov: DREAM
      study NCT01664611 and CRIC-RCT study NCT01817114) are investigating the effect of repeated
      RIC on LVEF function in patients with reduced ventricular function after an acute coronary
      event. Another study investigates the effect of repeated RIC on patients with severe heart
      failure and left ventricular assist device (IMPULSE study NCT02044471).

      So far, the effect of RIC on patients suffering from stable chronic ischemic heart failure is
      unknown. Furthermore, no registered studies have evaluated the effect of long-term RIC given
      as additive treatment to the standard medical therapy in patients with chronic ischemic heart
      failure.

      Hypothesis

      • We hypothesize, that the combination of anti-remodelling and anti-inflammatory properties
      together with improved endothelial function induced by repetitive RIC treatment translate
      into improved left ventricular function and better physical performance in subjects with CHF.

      Purpose

        -  To determine whether RIC applied on a daily basis for 4 weeks improves left ventricular
           function as assessed by cardiac magnetic resonance imaging (MRI) in subjects with CHF.

        -  To investigate whether RIC applied on a daily basis for 4 weeks improves muscle
           strength, cardiopulmonary exercise capacity and thrombocyte function, and changes blood
           biomarker levels of inflammation and heart failure in subjects with CHF.

        -  To investigate whether the above-mentioned measurements differ between patients with CHF
           and matched subjects after RIC applied on a daily basis for 4 weeks.

      Perspectives The present study will elucidate whether long-term RIC treatment induces
      beneficial effects in subjects with and without chronic ischemic heart failure in terms of
      improved left ventricular contractile function and exercise capacity, and whether long-term
      RIC treatment induces systemic anti-inflammatory effects in these subjects. Moreover, we find
      that the study can uncover some of the mechanisms behind RIC and thus potentially optimize
      future treatment for patients suffering, or at risk, from ischemic heart diseases.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Left ventricular ejection fraction assessed by MRI
time frame: 28±4 days
measure: Global and regional myocardial function by strain analysis assessed by MRI
time frame: 28±4 days
measure: Left ventricular mass and end-diastolic volume assessed by MRI
time frame: 28±4 days
measure: Cardiac output assessed by MRI
time frame: 28±4 days
measure: Cardiopulmonary exercise capacity assessed by staged exercise bicycle test and leg extension power rig test
time frame: 28±4 days
measure: Serology markers for heart failure
time frame: 28±4 days
measure: Serology inflammatory markers
time frame: 28±4 days
arm group label: Daily RIC
arm group type: Experimental
description: Daily ischemic conditioning treatment
intervention type: Other
intervention name: Daily ischemic conditioning treatment
description: RIC stimulus will be conducted as 4 x 5 minutes upper arm ischemia achieved by inflation of a blood pressure cuff to 200 mmHg and 5 minutes reperfusion between inflations. The procedure will be performed using the AutoRICTM (CellAegis Devices Inc., Toronto, Ontario, Canada).
arm group label: Daily RIC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hans Erik Bøtker, Prof.
role: Study Director
affiliation: Department of Cardiology, Aarhus University Hospital
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Heart Failure, Systolic