<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/NCT03791723</url>
  </required_header>
  <id_info>
    <org_study_id>APART-AF</org_study_id>
    <nct_id>NCT03791723</nct_id>
  </id_info>
  <brief_title>Effect of ARNI in Patients With Persistent AF and Enlarged Left Atrium After Catheter Ablation</brief_title>
  <acronym>APART-AF</acronym>
  <official_title>Efficacy and Safety of ARNI in Reversing Cardiac Remodeling After Catheter Ablation for Patient With Persistent Atrial Fibrillation and Enlarged Left Atrial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Second Affiliated Hospital of Chongqing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Second Affiliated Hospital of Chongqing Medical 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this clinical randomized trial is to evaluate the efficacy and safety of&#xD;
      Sacubitril/Valsartan compared with ARB in improving cardiac remodeling in patients With&#xD;
      Enlarged Left Atrium Diameter and Persistent AF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atrial fibrillation is one of the most common arrhythmia around the word. Prolonged atrial&#xD;
      fibrillation may lead to structural changes in the heart such as atrial enlargement, which is&#xD;
      an important risk factor for heart failure. Sacubitril/Valsartan is a new drug for the&#xD;
      treatment of heart failure, previous studies have shown that it has a good effect in&#xD;
      improving cardiac function. For patients with persistent atrial fibrillation and enlarged&#xD;
      left atrial, the effect of reversing cardiac remodeling after catheter ablation is unclear.&#xD;
      Some studies have described its positive effects in improving cardiac remodeling, but there&#xD;
      is still no large-scale randomized controlled trial to further confirm. The investigators&#xD;
      hypothesized that Sacubitril/Valsartan can reverse cardiac remodeling in patients with&#xD;
      persistent atrial fibrillation and enlarged left atrium compared with ARB after catheter&#xD;
      ablation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 1, 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>
    <intervention_model_description>two groups,group one is for Sacubitril/valsartan 200mg bid or tolerable maximum dose, group two is for valsartan 80mg qd or tolerable maximum dose.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Left atrial size changes compared to baseline levels</measure>
    <time_frame>6months and 12 months</time_frame>
    <description>Echocardiography was used to assess the size of the left atrium, and the changes in atrial structure and baseline levels were compared. The effective index was a gradual decrease in the atrium.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Freedom from AF or AT without the use of antiarrhythmic drugs at 12 months after a single ablation procedure.</measure>
    <time_frame>12 months</time_frame>
    <description>Confirmation of atrial fibrillation by electrocardiogram or dynamic electrocardiogram during follow-up. Patients with AF or AT that occurred in the first 3 months after the ablation (blanking period) were censored. Each episode that lasted &gt;30 s was regarded as a recurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>all-cause death</measure>
    <time_frame>12 months</time_frame>
    <description>all-cause death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first documented recurrence of atrial arrhythmias</measure>
    <time_frame>12 months</time_frame>
    <description>Time to first documented recurrence of atrial arrhythmias</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hospitalizations caused by heart failure</measure>
    <time_frame>12 months</time_frame>
    <description>Number of hospitalizations caused by heart failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause hospitalizations</measure>
    <time_frame>12 months</time_frame>
    <description>All-cause hospitalizations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients requires adjustment of the drug because of Hypotension</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients requires adjustment of the drug because of Hypotension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction</measure>
    <time_frame>12 months</time_frame>
    <description>A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Right atrial size changes compared to baseline levels</measure>
    <time_frame>12 months</time_frame>
    <description>Echocardiography was used to assess the size of the right atrium, and the changes in atrial structure and baseline levels were compared. The effective index was a gradual decrease in the atrium.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Cardiac Remodeling, Atrial</condition>
  <condition>Sacubitril/Valsartan</condition>
  <arm_group>
    <arm_group_label>Sacubitril/valsartan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After catheter ablation, during a single blind, run-in period, participants received placebo. Then started with 50 mg sacubitril/valsarta for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Valsartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40mg Valsartan twice daily qd for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sacubitril-Valsartan</intervention_name>
    <description>After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 50 mg LCZ696 for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.</description>
    <arm_group_label>Sacubitril/valsartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valsartan</intervention_name>
    <description>After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40 mg Valsartan daily (qd) for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.</description>
    <arm_group_label>Valsartan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with persistent atrial fibrillation undergoing catheter ablation within 2&#xD;
             weeks.&#xD;
&#xD;
          2. ≥18 and ≤75 years of age.&#xD;
&#xD;
          3. Left atrium diameter（LAD）≥35mm, With or without right atrium&#xD;
             diameter（RAD）≥40mm，diagnosed by Echocardiographic.&#xD;
&#xD;
          4. patient who are mentally and linguistically able to understand the aim of the trial&#xD;
             and to show sufficient compliance in following the trial protocol.&#xD;
&#xD;
          5. Patients receiving ACE inhibitors (ACEI), angiotensin receptor blockers (ARB) and/or a&#xD;
             beta blockers must be on a stable dose of these medications stable for the 1 month&#xD;
             period prior to Visit.&#xD;
&#xD;
          6. Patients with a controlled systolic BP, defined as a target systolic BP less than 140&#xD;
             mm Hg; participants with BP up to and including 160 mmHg are eligible for enrollment&#xD;
             if they are on three or more medications to control BP at randomization.&#xD;
&#xD;
          7. Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the&#xD;
             Modification of Diet in Renal Disease formula).&#xD;
&#xD;
          8. Patients with a potassium ≤5.2 mmol/l at Visit 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with prosthetic valves.&#xD;
&#xD;
          2. Any previous LA suigery.&#xD;
&#xD;
          3. Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within&#xD;
             3 months , or urgent percutaneous coronary intervention within 3 months or and&#xD;
             elective PCI within 30 days prior to entry.&#xD;
&#xD;
          4. Presence of hemodynamically significant mitral and /or aortic valve disease.&#xD;
&#xD;
          5. Presence of hemodynamically significant obstructive lesions of left ventricular&#xD;
             outflow tract, including aortic stenosis.&#xD;
&#xD;
          6. Current acute decompensated HF requiring therapy.&#xD;
&#xD;
          7. Allergic to drugs or active ingredients (shakuba, valsartan) or any excipients。&#xD;
&#xD;
          8. Patients with previous history of angioedema associated with ACEI or ARB treatment.&#xD;
&#xD;
          9. Patient with hereditary or idiopathic angioedema.&#xD;
&#xD;
         10. patient with severe liver damage, biliary cirrhosis and cholestasis.&#xD;
&#xD;
         11. Patient with Renal artery stenosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>ZHIYU LING, MD</last_name>
    <phone>+8613512362075</phone>
    <email>lingzy1977@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>YANPING XU</last_name>
    <phone>+86-023-63693079</phone>
  </overall_contact_backup>
  <reference>
    <citation>Almufleh A, Marbach J, Chih S, Stadnick E, Davies R, Liu P, Mielniczuk L. Ejection fraction improvement and reverse remodeling achieved with Sacubitril/Valsartan in heart failure with reduced ejection fraction patients. Am J Cardiovasc Dis. 2017 Dec 20;7(6):108-113. eCollection 2017.</citation>
    <PMID>29348971</PMID>
  </reference>
  <results_reference>
    <citation>Januzzi JL, Butler J, Fombu E, Maisel A, McCague K, Pina IL, Prescott MF, Riebman JB, Solomon S. Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF). Am Heart J. 2018 May;199:130-136. doi: 10.1016/j.ahj.2017.12.021. Epub 2018 Feb 13.</citation>
    <PMID>29754651</PMID>
  </results_reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>March 18, 2019</last_update_submitted>
  <last_update_submitted_qc>March 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Second Affiliated Hospital of Chongqing Medical University</investigator_affiliation>
    <investigator_full_name>Yuehui Yin</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>Atrial Fibrillation</keyword>
  <keyword>Cardiac Remodeling</keyword>
  <keyword>Sacubitril/Valsartan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Atrial Remodeling</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valsartan</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03791723
org study id: APART-AF
nct id: NCT03791723
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this clinical randomized trial is to evaluate the efficacy and safety of
      Sacubitril/Valsartan compared with ARB in improving cardiac remodeling in patients With
      Enlarged Left Atrium Diameter and Persistent AF.
Atrial fibrillation is one of the most common arrhythmia around the word. Prolonged atrial
      fibrillation may lead to structural changes in the heart such as atrial enlargement, which is
      an important risk factor for heart failure. Sacubitril/Valsartan is a new drug for the
      treatment of heart failure, previous studies have shown that it has a good effect in
      improving cardiac function. For patients with persistent atrial fibrillation and enlarged
      left atrial, the effect of reversing cardiac remodeling after catheter ablation is unclear.
      Some studies have described its positive effects in improving cardiac remodeling, but there
      is still no large-scale randomized controlled trial to further confirm. The investigators
      hypothesized that Sacubitril/Valsartan can reverse cardiac remodeling in patients with
      persistent atrial fibrillation and enlarged left atrium compared with ARB after catheter
      ablation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: two groups,group one is for Sacubitril/valsartan 200mg bid or tolerable maximum dose, group two is for valsartan 80mg qd or tolerable maximum dose.
primary purpose: Treatment
masking: None (Open Label)
measure: Left atrial size changes compared to baseline levels
time frame: 6months and 12 months
description: Echocardiography was used to assess the size of the left atrium, and the changes in atrial structure and baseline levels were compared. The effective index was a gradual decrease in the atrium.
measure: Freedom from AF or AT without the use of antiarrhythmic drugs at 12 months after a single ablation procedure.
time frame: 12 months
description: Confirmation of atrial fibrillation by electrocardiogram or dynamic electrocardiogram during follow-up. Patients with AF or AT that occurred in the first 3 months after the ablation (blanking period) were censored. Each episode that lasted >30 s was regarded as a recurrence.
measure: all-cause death
time frame: 12 months
description: all-cause death
measure: Time to first documented recurrence of atrial arrhythmias
time frame: 12 months
description: Time to first documented recurrence of atrial arrhythmias
measure: Number of hospitalizations caused by heart failure
time frame: 12 months
description: Number of hospitalizations caused by heart failure
measure: All-cause hospitalizations
time frame: 12 months
description: All-cause hospitalizations
measure: Number of patients requires adjustment of the drug because of Hypotension
time frame: 12 months
description: Number of patients requires adjustment of the drug because of Hypotension
measure: Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction
time frame: 12 months
description: A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.
measure: Right atrial size changes compared to baseline levels
time frame: 12 months
description: Echocardiography was used to assess the size of the right atrium, and the changes in atrial structure and baseline levels were compared. The effective index was a gradual decrease in the atrium.
arm group label: Sacubitril/valsartan
arm group type: Experimental
description: After catheter ablation, during a single blind, run-in period, participants received placebo. Then started with 50 mg sacubitril/valsarta for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.
arm group label: Valsartan
arm group type: Active Comparator
description: After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40mg Valsartan twice daily qd for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.
intervention type: Drug
intervention name: Sacubitril-Valsartan
description: After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 50 mg LCZ696 for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.
arm group label: Sacubitril/valsartan
intervention type: Drug
intervention name: Valsartan
description: After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40 mg Valsartan daily (qd) for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.
arm group label: Valsartan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: ZHIYU LING, MD
phone: +8613512362075
email: lingzy1977@163.com
last name: YANPING XU
phone: +86-023-63693079
citation: Almufleh A, Marbach J, Chih S, Stadnick E, Davies R, Liu P, Mielniczuk L. Ejection fraction improvement and reverse remodeling achieved with Sacubitril/Valsartan in heart failure with reduced ejection fraction patients. Am J Cardiovasc Dis. 2017 Dec 20;7(6):108-113. eCollection 2017.
PMID: 29348971
citation: Januzzi JL, Butler J, Fombu E, Maisel A, McCague K, Pina IL, Prescott MF, Riebman JB, Solomon S. Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF). Am Heart J. 2018 May;199:130-136. doi: 10.1016/j.ahj.2017.12.021. Epub 2018 Feb 13.
PMID: 29754651
responsible party type: Principal Investigator
investigator affiliation: The Second Affiliated Hospital of Chongqing Medical University
investigator full name: Yuehui Yin
investigator title: professor
mesh term: Atrial Fibrillation
mesh term: Atrial Remodeling
mesh term: Valsartan
mesh term: Sacubitril and valsartan sodium hydrate drug combination
sharing ipd: No