<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/NCT03821701</url>
  </required_header>
  <id_info>
    <org_study_id>XJTU1AF-CRF-2018-019</org_study_id>
    <nct_id>NCT03821701</nct_id>
  </id_info>
  <brief_title>Effect of Angiotensin-Neprilysin Inhibition (ARNI) on Prognosis of Chronic Heart Failure</brief_title>
  <official_title>A Multicenter, Randomized Controlled Trial of Angiotensin-Neprilysin Inhibition (ARNI) in the Chronic Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital Xi'an Jiaotong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Baoji Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital Xi'an Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>First Affiliated Hospital Xi'an Jiaotong University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study is a randomized controlled multicenter clinical trial, in which about 340 patients&#xD;
      with newly diagnosed or prior diagnosed chronic heart will be recruited. Patients will be&#xD;
      randomly divided into Angiotensin-Neprilysin Inhibition (ARNI) group and&#xD;
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) group.&#xD;
      All-cause death, cardiac death and re-hospitalization due to heart failure will be evaluated&#xD;
      in 1, 3, 6, 12 months after recruitment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic heart failure is associated with poor prognosis in cardiac patients, although&#xD;
      systemic effective drugs has been applied in these patients. European Society of Cardiology&#xD;
      (ESC) has recommended ARNI Sacubitril/Valsartan as first-line drugs in replacement of ACEI&#xD;
      (I, B) in 2016 for these patients. While American College of Cardiology and The American&#xD;
      Heart Association (ACC/AHA) made a first-line recommendation that patients with heart failure&#xD;
      due to reduced ejection fraction (HFrEF) could be administrated ARNI directly. Hence, we&#xD;
      apply this trial to find if ARNI could replace ACEI/ARB to provide insights for better&#xD;
      treatment of chronic heart failure in China. This study is a randomized controlled&#xD;
      multicenter clinical trial, in which about 340 patients with newly diagnosed or prior&#xD;
      diagnosed chronic heart will be recruited. Patients will be randomly divided into&#xD;
      Angiotensin-Neprilysin Inhibition (ARNI) group and ACEI/ARB group. All-cause death, cardiac&#xD;
      death and re-hospitalization due to heart failure will be evaluated in 1, 3, 6, 12 months&#xD;
      after recruitment. Other safety assessment including left ventricular ejection fraction&#xD;
      (LVEF), 6 minutes walk test will be followed up as well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Anticipated">January 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2021</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiovascular events</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months</time_frame>
    <description>Composite outcomes of all-cause death including cardiac death and re-hospitalization due to heart failure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Six-minutes walking test</measure>
    <time_frame>Test in 1, 3, 6, 12 months comparing to the baseline.</time_frame>
    <description>A test evaluating cardiac function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LVEF</measure>
    <time_frame>Test in 1, 3, 6, 12 months comparing to the baseline.</time_frame>
    <description>Left ventricular ejection fraction.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">340</enrollment>
  <condition>Chronic Heart Failure</condition>
  <arm_group>
    <arm_group_label>Newly diagnosed HFrEF ARNI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Newly diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Newly diagnosed HFrEF ACEI/ARB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Newly diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prior diagnosed HFrEF ARNI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prior diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prior diagnosed HFrEF ACEI/ARB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prior diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entresto</intervention_name>
    <description>Sacubitril Valsartan Sodium Tablets, 100mg bid, among whole study</description>
    <arm_group_label>Newly diagnosed HFrEF ARNI</arm_group_label>
    <arm_group_label>Prior diagnosed HFrEF ARNI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACEI/ARB</intervention_name>
    <description>Choose one of ACEI/ARB according to the clinical condition among the whole study.</description>
    <arm_group_label>Newly diagnosed HFrEF ACEI/ARB</arm_group_label>
    <arm_group_label>Prior diagnosed HFrEF ACEI/ARB</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  HFrEF, defined as LVEF≤40% and New York Heart Association (NYHA) class ≥ II.&#xD;
&#xD;
          -  Plasma NT-proBNP ≥ 600 pg/ml, or NT-proBNP ≥ 400 pg/ml if patients have been&#xD;
             hospitalized for heart failure in 12 months.&#xD;
&#xD;
          -  If patients have been taking ACEI/ARB at recruitment, a stable dose equivalent to at&#xD;
             least 10mg/day of enalapril will be required.&#xD;
&#xD;
          -  Volunteer for the study and sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptomatic hypotension, systolic blood pressure &lt; 95 mmHg at baseline.&#xD;
&#xD;
          -  eGFR &lt; 30 ml(/min*1.73m2) at baseline.&#xD;
&#xD;
          -  Serum potassium &gt; 5.4 mmol/L at baseline.&#xD;
&#xD;
          -  Contraindication of ACEI or ARB.&#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>Yihui Xiao</last_name>
    <role>Study Director</role>
    <affiliation>First Affiliated Hospital Xi'an Jiaotong University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yihui Xiao</last_name>
    <phone>+86 13572236467</phone>
    <phone_ext>+8613572236467</phone_ext>
    <email>sbw_514@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yihui Xiao</last_name>
    <phone>+8613572236467</phone>
    <phone_ext>+8613572236467</phone_ext>
    <email>sbw_514@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>First Affiliated Hospital of Xi'an Jiaotong University</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yihui Xiao</last_name>
      <phone>+8613572236467</phone>
      <email>sbw_514@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 27, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>August 5, 2019</last_update_submitted>
  <last_update_submitted_qc>August 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Shakurba valsartan</keyword>
  <keyword>Heart failure</keyword>
  <keyword>ACEI/ARB</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</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/NCT03821701
org study id: XJTU1AF-CRF-2018-019
nct id: NCT03821701
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a randomized controlled multicenter clinical trial, in which about 340 patients
      with newly diagnosed or prior diagnosed chronic heart will be recruited. Patients will be
      randomly divided into Angiotensin-Neprilysin Inhibition (ARNI) group and
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) group.
      All-cause death, cardiac death and re-hospitalization due to heart failure will be evaluated
      in 1, 3, 6, 12 months after recruitment.
Chronic heart failure is associated with poor prognosis in cardiac patients, although
      systemic effective drugs has been applied in these patients. European Society of Cardiology
      (ESC) has recommended ARNI Sacubitril/Valsartan as first-line drugs in replacement of ACEI
      (I, B) in 2016 for these patients. While American College of Cardiology and The American
      Heart Association (ACC/AHA) made a first-line recommendation that patients with heart failure
      due to reduced ejection fraction (HFrEF) could be administrated ARNI directly. Hence, we
      apply this trial to find if ARNI could replace ACEI/ARB to provide insights for better
      treatment of chronic heart failure in China. This study is a randomized controlled
      multicenter clinical trial, in which about 340 patients with newly diagnosed or prior
      diagnosed chronic heart will be recruited. Patients will be randomly divided into
      Angiotensin-Neprilysin Inhibition (ARNI) group and ACEI/ARB group. All-cause death, cardiac
      death and re-hospitalization due to heart failure will be evaluated in 1, 3, 6, 12 months
      after recruitment. Other safety assessment including left ventricular ejection fraction
      (LVEF), 6 minutes walk test will be followed up as well.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cardiovascular events
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
description: Composite outcomes of all-cause death including cardiac death and re-hospitalization due to heart failure
measure: Six-minutes walking test
time frame: Test in 1, 3, 6, 12 months comparing to the baseline.
description: A test evaluating cardiac function.
measure: LVEF
time frame: Test in 1, 3, 6, 12 months comparing to the baseline.
description: Left ventricular ejection fraction.
arm group label: Newly diagnosed HFrEF ARNI
arm group type: Experimental
description: Newly diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study.
arm group label: Newly diagnosed HFrEF ACEI/ARB
arm group type: Active Comparator
description: Newly diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study.
arm group label: Prior diagnosed HFrEF ARNI
arm group type: Experimental
description: Prior diagnosed HFrEF patients will be administered ARNI Entresto according to the clinical condition among the whole study.
arm group label: Prior diagnosed HFrEF ACEI/ARB
arm group type: Active Comparator
description: Prior diagnosed HFrEF patients will be administered ACEI/ARB according to the clinical condition among the whole study.
intervention type: Drug
intervention name: Entresto
description: Sacubitril Valsartan Sodium Tablets, 100mg bid, among whole study
arm group label: Newly diagnosed HFrEF ARNI
arm group label: Prior diagnosed HFrEF ARNI
intervention type: Drug
intervention name: ACEI/ARB
description: Choose one of ACEI/ARB according to the clinical condition among the whole study.
arm group label: Newly diagnosed HFrEF ACEI/ARB
arm group label: Prior diagnosed HFrEF ACEI/ARB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yihui Xiao
role: Study Director
affiliation: First Affiliated Hospital Xi'an Jiaotong University
last name: Yihui Xiao
phone: +86 13572236467
phone ext: +8613572236467
email: sbw_514@163.com
last name: Yihui Xiao
phone: +8613572236467
phone ext: +8613572236467
email: sbw_514@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Sacubitril and valsartan sodium hydrate drug combination