<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/NCT01678794</url>
  </required_header>
  <id_info>
    <org_study_id>09-003284</org_study_id>
    <secondary_id>1R01HL084155-01A2</secondary_id>
    <nct_id>NCT01678794</nct_id>
  </id_info>
  <brief_title>CR Aim #2 - AT1 Receptor Blockade &amp; ACE Inhibition Effect on Humoral Function</brief_title>
  <official_title>Define in Humans With Compensated CHF and Renal Dysfunction, the Modulating Action of Chronic AT1 Receptor Blockade in Addition to ACE Inhibition on Cardiorenal and Humoral Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis&#xD;
      upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and&#xD;
      cGMP pathway.&#xD;
&#xD;
      The belief is that the chronic AT1 receptor blockade in subjects with compensated CHF and&#xD;
      renal dysfunction will improve renal function with increased sodium excretion, glomerular&#xD;
      filtration rate and effective renal plasma flow and renal function reserve as compared to the&#xD;
      response of placebo-treated subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      IRB # 09-003284, &quot;Specific Aims 2: Define in humans with compensated CHF and renal&#xD;
      dysfunction, the modulating action of chronic AT1 receptor blockade in addition to ACE&#xD;
      inhibition on cardiorenal and humoral function&quot;, involving 12 weeks of study drug&#xD;
      (Candesartan or placebo) starting at 4 mg daily and doubling every 2 weeks to 16 mg, if&#xD;
      tolerated. Safety labs are performed one week after each dose increase (end of weeks 1, 3 and&#xD;
      5), and in week 10 of the study. Participants are monitoring their blood pressure weekly, and&#xD;
      are aware to watch for symptoms of hypotension (lightheadedness, dizziness, blurred vision).&#xD;
      Renal clearance testing and ECHO are performed at the start and end of the 12 weeks of study&#xD;
      medication in the 5-Domitilla Clinical Research Unit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2012</start_date>
  <completion_date type="Actual">June 29, 2016</completion_date>
  <primary_completion_date type="Actual">June 29, 2016</primary_completion_date>
  <phase>Phase 1/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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Glomerular Filtration Rate</measure>
    <time_frame>baseline to 3 months</time_frame>
    <description>Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Urinary Sodium Excretion</measure>
    <time_frame>baseline to 3 months</time_frame>
    <description>Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Cardiorenal Syndrome (CRS)</condition>
  <arm_group>
    <arm_group_label>Candesartan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Candesartan</intervention_name>
    <description>4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
    <arm_group_label>Candesartan</arm_group_label>
    <other_name>Atacand</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Left ventricular ejection fraction of equal or less than 40% assessed by&#xD;
             echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months.&#xD;
&#xD;
          -  Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no&#xD;
             change in NYHA symptoms over the past 3 months, on stable doses of ACE inhibitor, beta&#xD;
             blocker, digoxin and furosemide over the last 4 weeks and no episode of decompensated&#xD;
             CHF over the past 6 months.&#xD;
&#xD;
          -  Calculated creatinine clearance of equal or less than 80 ml/min and greater than 20&#xD;
             ml/min, using the MDRD formula assessed within the past 48 months and a confirmatory&#xD;
             calculated creatinine clearance equal or less than 80 ml/min and greater than 20&#xD;
             ml/min at the time of enrollment.&#xD;
&#xD;
        Subjects who are already taking AT1 receptor blocker will be excluded. Aldosterone&#xD;
        antagonist, antiarrhythmic medications and other vasodilators will be allowed; however, all&#xD;
        medications must be at stable doses 4 weeks prior to enrollment. Subjects taking&#xD;
        nonsteroidal anti-inflammatory drugs (NSAIDs) except aspirin will not be able to increase&#xD;
        their medication dose for the duration of the study. Subjects will be excluded if they have&#xD;
        had a prior diagnosis of intrinsic renal disease, including renal artery stenosis of &gt; 50%,&#xD;
        or if they meet any one of the exclusion criteria listed below.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior diagnosis of intrinsic renal diseases including renal artery stenosis of &gt; 50%&#xD;
&#xD;
          -  Peritoneal or hemodialysis within 90 days or anticipation that dialysis or&#xD;
             ultrafiltration of any form will be required during the study period&#xD;
&#xD;
          -  Hospitalization for decompensated CHF during the past 6 months&#xD;
&#xD;
          -  Subjects that are taking AT1 receptor blockers&#xD;
&#xD;
          -  Myocardial infarction within 6 months of screening&#xD;
&#xD;
          -  Unstable angina within 6 months of screening, or any evidence of myocardial ischemia&#xD;
&#xD;
          -  Significant valvular stenosis, hypertrophic, restrictive or obstructive&#xD;
             cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy&#xD;
             proven active myocarditis&#xD;
&#xD;
          -  Severe congenital heart diseases&#xD;
&#xD;
          -  Sustained ventricular tachycardia or ventricular fibrillation within 14 days of&#xD;
             screening&#xD;
&#xD;
          -  Second or third degree heart block without a permanent cardiac pacemaker&#xD;
&#xD;
          -  Stroke within 3 months of screening, or other evidence of significantly compromised&#xD;
             CNS perfusion&#xD;
&#xD;
          -  ALT &gt;1.5 times the upper limit of normal&#xD;
&#xD;
          -  Serum sodium of &lt; 125 mEq/dL or &gt; 160 mEq/dL&#xD;
&#xD;
          -  Serum potassium of &lt; 3.5 mEq/dL or &gt; 5.7 mEq/dL&#xD;
&#xD;
          -  Serum digoxin level of &gt; 2.0 ng/ml&#xD;
&#xD;
          -  Hemoglobin &lt; 9 gm/dl&#xD;
&#xD;
          -  Other acute or chronic medical conditions or laboratory abnormality which may increase&#xD;
             the risks associated with study participation or may interfere with interpretation of&#xD;
             the data&#xD;
&#xD;
          -  Received an investigational drug within 1 month prior to dosing&#xD;
&#xD;
          -  Patients with an allergy to iodine.&#xD;
&#xD;
          -  Female subject who is pregnant or breastfeeding&#xD;
&#xD;
          -  In the opinion of the investigator, is unlikely to comply with the study protocol or&#xD;
             is unsuitable for any reasons&#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>Horng H. Chen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <results_first_submitted>October 20, 2021</results_first_submitted>
  <results_first_submitted_qc>October 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 18, 2021</results_first_posted>
  <last_update_submitted>October 20, 2021</last_update_submitted>
  <last_update_submitted_qc>October 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Horng Chen</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>Chronic heart failure (CHF)</keyword>
  <keyword>cardiac and renal dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardio-Renal Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Candesartan</mesh_term>
    <mesh_term>Candesartan cilexetil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 17, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT01678794/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Candesartan</title>
          <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Candesartan</title>
          <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="33"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.5" spread="10.4"/>
                    <measurement group_id="B2" value="69.3" spread="14.2"/>
                    <measurement group_id="B3" value="68.9" spread="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Glomerular Filtration Rate</title>
        <description>Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2</description>
        <time_frame>baseline to 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Candesartan</title>
            <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Glomerular Filtration Rate</title>
          <description>Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2</description>
          <units>ml/min/1.73 m2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5" lower_limit="-14.5" upper_limit="3.5"/>
                    <measurement group_id="O2" value="1.00" lower_limit="-8.00" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.26</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Urinary Sodium Excretion</title>
        <description>Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min</description>
        <time_frame>baseline to 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Candesartan</title>
            <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Urinary Sodium Excretion</title>
          <description>Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min</description>
          <units>mEq/min</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.50" lower_limit="-30.50" upper_limit="48.50"/>
                    <measurement group_id="O2" value="10.00" lower_limit="-53.00" upper_limit="66.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.67</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected from baseline to end of study, approximately 3 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Candesartan</title>
          <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Subjects received 4 mg once a day up to 13 day. Dose was doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Increased plasma creatinine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Joint pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Lightheadness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chest tightness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Horng H. Chen, M.D.</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-284-8896</phone>
      <email>chen.horng@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01678794
org study id: 09-003284
secondary id: 1R01HL084155-01A2
nct id: NCT01678794
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis
      upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and
      cGMP pathway.

      The belief is that the chronic AT1 receptor blockade in subjects with compensated CHF and
      renal dysfunction will improve renal function with increased sodium excretion, glomerular
      filtration rate and effective renal plasma flow and renal function reserve as compared to the
      response of placebo-treated subjects.
IRB # 09-003284, "Specific Aims 2: Define in humans with compensated CHF and renal
      dysfunction, the modulating action of chronic AT1 receptor blockade in addition to ACE
      inhibition on cardiorenal and humoral function", involving 12 weeks of study drug
      (Candesartan or placebo) starting at 4 mg daily and doubling every 2 weeks to 16 mg, if
      tolerated. Safety labs are performed one week after each dose increase (end of weeks 1, 3 and
      5), and in week 10 of the study. Participants are monitoring their blood pressure weekly, and
      are aware to watch for symptoms of hypotension (lightheadedness, dizziness, blurred vision).
      Renal clearance testing and ECHO are performed at the start and end of the 12 weeks of study
      medication in the 5-Domitilla Clinical Research Unit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Glomerular Filtration Rate
time frame: baseline to 3 months
description: Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2
measure: Change in Urinary Sodium Excretion
time frame: baseline to 3 months
description: Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min
arm group label: Candesartan
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Candesartan
description: 4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated
arm group label: Candesartan
other name: Atacand
intervention type: Drug
intervention name: Placebo
description: 4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Horng H. Chen, M.D.
role: Principal Investigator
affiliation: Mayo Foundation
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Horng Chen
investigator title: PI
mesh term: Cardio-Renal Syndrome
mesh term: Candesartan
mesh term: Candesartan cilexetil
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 