<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/NCT03797001</url>
  </required_header>
  <id_info>
    <org_study_id>REDHART2 HM20014686</org_study_id>
    <nct_id>NCT03797001</nct_id>
  </id_info>
  <brief_title>Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2</brief_title>
  <acronym>REDHART2</acronym>
  <official_title>The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      REDHART2 is a randomized, double-blinded, placebo-controlled trial to determine the effects&#xD;
      of Anakinra on peak aerobic exercise capacity measured with a cardiopulmonary test after 24&#xD;
      weeks in patients with recently decompensated systolic heart failure and increased systemic&#xD;
      inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The REDHART2 (REcently Decompensated Heart failure Anakinra Response 2 Trial) study is a&#xD;
      phase II clinical trial of anakinra or placebo to determine improvement in aerobic exercise&#xD;
      capacity (by measuring maximal oxygen uptake (VO2)) in patients with recently decompensated&#xD;
      systolic heart failure (HF). The recently completed pilot REDHART study showed anakinra&#xD;
      treatment for 12 weeks led to a significant improvement in peak aerobic exercise capacity,&#xD;
      whereas anakinra treatment for 2 weeks did not, and no significant changes were seen in&#xD;
      placebo. The REDHART2 study is designed to expand and confirm the beneficial effect of&#xD;
      sustained anakinra treatment (24 weeks) on peak VO2, and to explore the potential effect size&#xD;
      on hospital readmissions for HF. The rationale of Interleukin-1 (IL-1) blockade with anakinra&#xD;
      in heart failure stems from the evidence of a) reduced adverse cardiac remodeling and heart&#xD;
      failure in animal models of acute myocardial infarction (AMI); b) reduced incidence of heart&#xD;
      failure in patients with ST-segment elevation AMI; c) enhanced IL-1 activity in patients with&#xD;
      heart failure, d) quenching of the acute inflammatory response in patients with acute&#xD;
      decompensated heart failure, e) direct cardiodepressant effects of IL-1 in animal models, f)&#xD;
      improved exercise capacity in pilot studies including patients with stable systolic heart&#xD;
      failure, stable diastolic heart failure, and, recently decompensated systolic heart failure&#xD;
      in the pilot REDHART study. Patients will be randomized 2:1 to active treatment, such that&#xD;
      patients will be twice as likely to receive anakinra versus placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 4, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>changes in peak oxygen consumption (VO2)</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>changes in peak oxygen consumption (VO2) after 24 weeks of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>changes in peak VO2 at earlier endpoints</measure>
    <time_frame>baseline - 6 weeks and baseline - 12 weeks</time_frame>
    <description>changes in peak VO2 at earlier endpoints (6 and 12 weeks)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>echocardiography assessments</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>evaluation of heart function by standard echocardiography assessments at 24 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hemodynamic assessments</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>estimates of arterial elastance at 6, 12 and 24 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessments</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>Duke Activity Status Index will be administered at 6, 12 and 24 weeks to provide patient perception of changes. Responses are yes or no, with yes responses corresponding to better clinical condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker - high sensitivity C-reactive protein (CRP)</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>The change in blood levels of CRP will be measured from baseline to 24 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker - N-terminal pro b-type Natriuretic Peptide (NT-proBNP)</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>The change in blood levels of NT-proBNP will be measured from baseline to 24 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Outcome - cardiac death</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>Instances of cardiac death during the study will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Outcome - hospitalization for heart failure</measure>
    <time_frame>baseline - 24 weeks</time_frame>
    <description>Instances of hospitalization for heart failure during the study will be recorded</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">102</enrollment>
  <condition>Heart Failure, Systolic</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>anakinra</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anakinra subcutaneous injection, 100 mg daily for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo subcutaneous injection, daily for 24 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anakinra</intervention_name>
    <description>100 mg subcutaneous injection, daily for 24 weeks</description>
    <arm_group_label>anakinra</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>subcutaneous injection, daily for 24 weeks</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All 6 criteria need to be met for enrollment of the patient in the study&#xD;
&#xD;
          1. Primary diagnosis for hospitalization is decompensated heart failure established as&#xD;
             the finding at admission of both conditions listed below:&#xD;
&#xD;
               -  dyspnea or respiratory distress or tachypnea at rest or with minimal exertion;&#xD;
&#xD;
               -  evidence of elevated cardiac filling pressure or pulmonary congestion (at least&#xD;
                  one of the conditions must be met):&#xD;
&#xD;
               -  pulmonary congestion/edema at physical exam OR chest XRay;&#xD;
&#xD;
               -  plasma BNP levels ≥200 pg/mL;&#xD;
&#xD;
               -  invasive measurement of left ventricular end-diastolic pressure &gt;18 mmHg or of&#xD;
                  pulmonary artery occluding pressure (wedge) &gt;16 mmHg.&#xD;
&#xD;
          2. The patient has a prior documentation of impaired left ventricular systolic function&#xD;
             (ejection fraction ≤40%) at most recent assessment by any imaging modality (within 12&#xD;
             months).&#xD;
&#xD;
          3. The patient is now clinically stable, euvolemic, and meets standard criteria for&#xD;
             hospital discharge as documented by all the 3 conditions listed below:&#xD;
&#xD;
               -  absence of dyspnea or pulmonary congestion/distress at rest;&#xD;
&#xD;
               -  absence of pitting edema in the lower extremities, or in any other region;&#xD;
&#xD;
               -  stable hemodynamic parameters (blood pressure, heart rate).&#xD;
&#xD;
          4. The patient is of age ≥21 years old, and is willing and able to provide written&#xD;
             informed consent.&#xD;
&#xD;
          5. The patient is willing and able to comply with the protocol (i.e.,&#xD;
             self-administration, or exercise test).&#xD;
&#xD;
          6. The patient has screening high sensitivity plasma C-reactive protein levels (hsCRP) &gt;2&#xD;
             mg/L.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects will not be eligible if they meet any of the following 15 exclusion criteria.&#xD;
&#xD;
          1. The primary diagnosis for admission is NOT decompensated heart failure, including&#xD;
             diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or&#xD;
             brady-arrhythmias.&#xD;
&#xD;
          2. Concomitant clinically significant comorbidities that would interfere with the&#xD;
             execution or interpretation of the study including but not limited to acute coronary&#xD;
             syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or&#xD;
             brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders&#xD;
             affecting respiration.&#xD;
&#xD;
          3. Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve&#xD;
             surgeries.&#xD;
&#xD;
          4. Previous or planned implantation of left ventricular assist devices or heart&#xD;
             transplant.&#xD;
&#xD;
          5. Chronic use of intravenous inotropes.&#xD;
&#xD;
          6. Recent (&lt;14 days) use of immunosuppressive or anti-inflammatory drugs (including oral&#xD;
             corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including&#xD;
             inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs).&#xD;
&#xD;
          7. Chronic inflammatory disorder (including but not limited to rheumatoid arthritis,&#xD;
             systemic lupus erythematosus).&#xD;
&#xD;
          8. Active infection (of any type), including chronic/recurrent infectious disease (i.e.&#xD;
             HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA.&#xD;
&#xD;
          9. Active malignancy - excluding carcinoma in situ [any location] or localized&#xD;
             non-melanoma skin cancer.&#xD;
&#xD;
         10. Any comorbidity limiting survival or ability to complete the study.&#xD;
&#xD;
         11. Stage V kidney disease or on renal-replacement therapy.&#xD;
&#xD;
         12. Neutropenia (&lt;1,500/mm3 or &lt;1,000/mm3 in African-American patients).&#xD;
&#xD;
         13. Pregnancy.&#xD;
&#xD;
         14. Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other&#xD;
             non-cardiac limitations (i.e., peak respiratory exchange ratio VCO2/VO2 [RER]&lt;1.0,&#xD;
             reflecting sub-maximal test) that limit maximum exertion during CPX obtained during&#xD;
             the baseline testing.&#xD;
&#xD;
         15. Hypersensitivity to Kineret or to E. coli derived products. 16) Evidence of COVID19&#xD;
             within the last 60 days or recent (21 days) exposure to close personal contact.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benjamin Van Tassell, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Benjamin Van Tassell, PharmD</last_name>
    <phone>804-828-4583</phone>
    <email>bvantassell@vcu.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benjamin Van Tassell, PharmD</last_name>
      <phone>804-828-4583</phone>
      <email>bvantassell@vcu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>heart failure</keyword>
  <keyword>inflammation</keyword>
  <keyword>anakinra</keyword>
  <keyword>exercise capacity</keyword>
  <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>
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Systolic Murmurs</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interleukin 1 Receptor Antagonist Protein</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/NCT03797001
org study id: REDHART2 HM20014686
nct id: NCT03797001
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
REDHART2 is a randomized, double-blinded, placebo-controlled trial to determine the effects
      of Anakinra on peak aerobic exercise capacity measured with a cardiopulmonary test after 24
      weeks in patients with recently decompensated systolic heart failure and increased systemic
      inflammation.
The REDHART2 (REcently Decompensated Heart failure Anakinra Response 2 Trial) study is a
      phase II clinical trial of anakinra or placebo to determine improvement in aerobic exercise
      capacity (by measuring maximal oxygen uptake (VO2)) in patients with recently decompensated
      systolic heart failure (HF). The recently completed pilot REDHART study showed anakinra
      treatment for 12 weeks led to a significant improvement in peak aerobic exercise capacity,
      whereas anakinra treatment for 2 weeks did not, and no significant changes were seen in
      placebo. The REDHART2 study is designed to expand and confirm the beneficial effect of
      sustained anakinra treatment (24 weeks) on peak VO2, and to explore the potential effect size
      on hospital readmissions for HF. The rationale of Interleukin-1 (IL-1) blockade with anakinra
      in heart failure stems from the evidence of a) reduced adverse cardiac remodeling and heart
      failure in animal models of acute myocardial infarction (AMI); b) reduced incidence of heart
      failure in patients with ST-segment elevation AMI; c) enhanced IL-1 activity in patients with
      heart failure, d) quenching of the acute inflammatory response in patients with acute
      decompensated heart failure, e) direct cardiodepressant effects of IL-1 in animal models, f)
      improved exercise capacity in pilot studies including patients with stable systolic heart
      failure, stable diastolic heart failure, and, recently decompensated systolic heart failure
      in the pilot REDHART study. Patients will be randomized 2:1 to active treatment, such that
      patients will be twice as likely to receive anakinra versus placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: changes in peak oxygen consumption (VO2)
time frame: baseline - 24 weeks
description: changes in peak oxygen consumption (VO2) after 24 weeks of treatment
measure: changes in peak VO2 at earlier endpoints
time frame: baseline - 6 weeks and baseline - 12 weeks
description: changes in peak VO2 at earlier endpoints (6 and 12 weeks)
measure: echocardiography assessments
time frame: baseline - 24 weeks
description: evaluation of heart function by standard echocardiography assessments at 24 weeks
measure: hemodynamic assessments
time frame: baseline - 24 weeks
description: estimates of arterial elastance at 6, 12 and 24 weeks
measure: Quality of Life Assessments
time frame: baseline - 24 weeks
description: Duke Activity Status Index will be administered at 6, 12 and 24 weeks to provide patient perception of changes. Responses are yes or no, with yes responses corresponding to better clinical condition.
measure: Biomarker - high sensitivity C-reactive protein (CRP)
time frame: baseline - 24 weeks
description: The change in blood levels of CRP will be measured from baseline to 24 weeks.
measure: Biomarker - N-terminal pro b-type Natriuretic Peptide (NT-proBNP)
time frame: baseline - 24 weeks
description: The change in blood levels of NT-proBNP will be measured from baseline to 24 weeks.
measure: Clinical Outcome - cardiac death
time frame: baseline - 24 weeks
description: Instances of cardiac death during the study will be recorded
measure: Clinical Outcome - hospitalization for heart failure
time frame: baseline - 24 weeks
description: Instances of hospitalization for heart failure during the study will be recorded
arm group label: anakinra
arm group type: Experimental
description: Anakinra subcutaneous injection, 100 mg daily for 24 weeks
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo subcutaneous injection, daily for 24 weeks
intervention type: Drug
intervention name: Anakinra
description: 100 mg subcutaneous injection, daily for 24 weeks
arm group label: anakinra
intervention type: Drug
intervention name: Placebo
description: subcutaneous injection, daily for 24 weeks
arm group label: placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Benjamin Van Tassell, PharmD
role: Principal Investigator
affiliation: Virginia Commonwealth University
last name: Benjamin Van Tassell, PharmD
phone: 804-828-4583
email: bvantassell@vcu.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Heart Failure, Systolic
mesh term: Inflammation
mesh term: Systolic Murmurs
mesh term: Interleukin 1 Receptor Antagonist Protein