xml: <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/NCT06021808</url>
    </required_header>
    <id_info>
      <org_study_id>2023-2059</org_study_id>
      <nct_id>NCT06021808</nct_id>
    </id_info>
    <brief_title>LAA Clipping Versus NOACs to Prevent Stroke in Non-paroxysmal Atrial Fibrillation.</brief_title>
    <official_title>Epicardial Left Atrial Appendage Clipping Versus Novel Oral Anticoagulants to Reduce Stroke Risk in Non-paroxysmal Atrial Fibrillation: a Multicenter Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>China National Center for Cardiovascular Diseases</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>China National Center for Cardiovascular Diseases</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>
        This trial is designed to examine the hypothesis that thoracoscopic LAA clipping is superior&#xD;
        to NOACs for stroke, systemic embolism, all-cause mortality, major bleeding events and&#xD;
        clinically relevant nonmajor bleeding events in AF patients at high risk of embolism&#xD;
        (CHA2DS2-VASc ≥2 in men and ≥3 in women) that are not undergoing ablation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia disease, and the incidence&#xD;
        of AF increases markedly with age and approximately doubles with each decade. According to&#xD;
        the previous study, the incidence of stroke were five times in patients with AF than those in&#xD;
        the general population. Systemic oral anticoagulant is a well-established,&#xD;
        guideline-recommended therapy for the prevention of ischemic stroke in patients with&#xD;
        nonvalvular AF at high risk of embolism (CHA2DS2-VASc scores ≥2 in men and ≥3 in women), and&#xD;
        the guidelines recommend that the novel oral anticoagulants (NOACs) be preferred (Class I,&#xD;
        Level of evidence A). However, a significant proportion of patients with nonvalvular AF have&#xD;
        difficulties in long-term oral anticoagulant therapy, due to medication adherence and&#xD;
        contraindications to oral anticoagulants. Also, several randomized controlled trials&#xD;
        indicated that bleeding risk remained high with novel oral anticoagulants. Therefore, it is&#xD;
        essential to explore alternative treatment strategies for stroke prevention in patients with&#xD;
        nonvalvular AF.&#xD;
  &#xD;
        It has been reported that the left atrial appendage (LAA) is suspected as a vital source of&#xD;
        cerebral emboli and may lead to ischemic stroke, removal or closure of the LAA may be an&#xD;
        alternative to oral anticoagulants. Various surgical or interventional approaches have been&#xD;
        developed to close or occlude LAA to prevent stroke in AF patients, such as percutaneous LAA&#xD;
        occlusion, suture ligation, and surgical excision. However, these techniques suffer from&#xD;
        incomplete LAA closure or the presence of residual blood flow, which can lead to thrombosis&#xD;
        and stroke. Thoracoscopic LAA clip, on the other hand, cloud block blood flow between the LAA&#xD;
        and the left atrium (LA), achieving isolation of LAA and preventing thrombi and strokes. A&#xD;
        previous study has demonstrated a high 95% success rate of LAA clipping without&#xD;
        operation-related complications, and freedom from stroke was 99.1% at a median follow-up of&#xD;
        20 months. Therefore, LAA clipping is an effective and durable method in stroke prevention.&#xD;
        However, currently high-quality RCTs are lacking to support the superiority of LAA clipping&#xD;
        compared with NOACs in terms of stroke prevention and safety. In this trial, the&#xD;
        investigators designed a multicenter prospective RCT to compare the efficacy and safety of&#xD;
        thoracoscopic LAA clipping and NOACs in patients with non-paroxysmal AF.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">November 2027</completion_date>
    <primary_completion_date type="Anticipated">October 2027</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>Prevention</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Rate of composite endpoint</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Stroke, systemic embolism, all-cause mortality, major bleeding event, and clinically relevant non-major bleeding event.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Rate of stroke</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Acute episodes of focal or global neurological dysfunction due to cerebral, spinal cord or retinal vascular injury from haemorrhage or infarction. Symptoms or signs must have lasted ≥ 24 hours, or symptoms/signs may have lasted less than 24 hours if demonstrated by CT, MRI, or autopsy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of systemic embolism</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Confirmed by imaging or angiography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of all-cause mortality</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Deaths from all causes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of major bleeding event</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>fatal haemorrhage, and/or&#xD;
  Symptomatic haemorrhage in a critical area or organ, such as intracranial, intravertebral, intraocular, retroperitoneal, intra-articular or intrapericardial, or intramuscular haemorrhage leading to osteofascial compartment syndrome, and/or 3. haemorrhage that results in a fall in haemoglobin level of 2.0 g/dL or more, or that results in the importation of two or more units of whole blood or red blood cells.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of clinically relevant non-major bleeding event</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Bleeding events that do not meet the criteria for an ISTH major bleeding event but requires hospitalisation or a change in antithrombotic treatment strategy or requires invasive management.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of surgery-related complications</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Incidence of in-hospital death, in-hospital stroke, intermediate small-incision open thoracotomy or median open thoracotomy, and postoperative re-intervention due to hemorrhage, pneumothorax, and pyothorax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of minor bleeding events</measure>
      <time_frame>At 24-month after intervention</time_frame>
      <description>Bleeding events that do not meet the ISTH criteria for a major bleeding event, do not meet the criteria for a clinically relevant non-major bleeding event, and do not require the subject to seek additional assistance from medical care.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">290</enrollment>
    <condition>Non-paroxysmal Atrial Fibrillation</condition>
    <arm_group>
      <arm_group_label>LAA clipping group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In this arm, participants are performed thoracoscopic LAA clipping.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NOACs group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients randomized to NOAC therapy will begin long-term oral administration of NOACs immediately after enrollment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Thoracoscopic LAA clipping</intervention_name>
      <description>The surgeons measured the length of the base of the LAA, an appropriately sized LAA clip is then inserted with the aid of a thoracoscope and placed parallel to the base of the LAA.</description>
      <arm_group_label>LAA clipping group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Novel oral anticoagulant</intervention_name>
      <description>For patients with creatinine clearance ≥50 ml/min, oral rivaroxaban 20 mg daily was administered, whereas for patients with creatinine clearance between 30-49 ml/min, oral rivaroxaban 15 mg daily was administered.</description>
      <arm_group_label>NOACs group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age ≥ 18 years.&#xD;
  &#xD;
            -  Persistent or long-standing persistent AF documented by medical history or direct&#xD;
               electrocardiogram.&#xD;
  &#xD;
            -  CHA2DS2-VASc ≥2 in men and ≥3 in women.&#xD;
  &#xD;
            -  Agree to perform thoracoscopic LAA occlusion procedure.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  With electrical cardioversion or ablation intent.&#xD;
  &#xD;
            -  Other heart diseases with surgical indications.&#xD;
  &#xD;
            -  Ischemic stroke and other cardiac embolic events within 30 days.&#xD;
  &#xD;
            -  Major clinical bleeding event within 30 days.&#xD;
  &#xD;
            -  Contraindications to anticoagulation.&#xD;
  &#xD;
            -  Intracardiac thrombus.&#xD;
  &#xD;
            -  Left ventricular ejection fraction (LVEF) &lt; 30%.&#xD;
  &#xD;
            -  Active systemic infection or infective endocarditis or pericarditis&#xD;
  &#xD;
            -  Severe liver disease (acute clinical hepatitis, chronic active hepatitis, cirrhosis)&#xD;
               or alanine transaminase (ALT)/ aspartate transaminase (AST) greater than 3 times the&#xD;
               upper limit of normal value.&#xD;
  &#xD;
            -  Severe renal insufficiency (eGFR ≤ 30mL/min).&#xD;
  &#xD;
            -  Other diseases requiring oral anticoagulants.&#xD;
  &#xD;
            -  Active aortic plaque.&#xD;
  &#xD;
            -  Acute coronary syndrome within 3 months.&#xD;
  &#xD;
            -  Symptomatic carotid artery stenosis.&#xD;
  &#xD;
            -  Patients requiring dual antiplatelet drug therapy.&#xD;
  &#xD;
            -  Previous cardiac and left lung surgery.&#xD;
  &#xD;
            -  Severe left pleural and pericardial adhesions.&#xD;
  &#xD;
            -  Pregnant or breastfeeding patients.&#xD;
  &#xD;
            -  Metal allergies.&#xD;
  &#xD;
            -  Terminal illness with a life expectancy of less than 2 years.&#xD;
  &#xD;
            -  Participation in other clinical studies at the time of enrollment.&#xD;
  &#xD;
            -  Refuse to participate in this study.&#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>Zhe Zheng, MD,PhD</last_name>
      <role>Study Chair</role>
      <affiliation>Fuwai Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhe Zheng, MD,PhD</last_name>
      <phone>+86-010-88396051</phone>
      <email>zhengzhe@fuwai.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Chunyu Yu, MD</last_name>
      <email>yuchunyu@fuwai.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>China National Center for Cardiovascular Diseases</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100037</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Zhe Zheng, M.D., Ph.D.</last_name>
        <phone>8610-8839-6051</phone>
        <email>zhengzhe@fuwai.com</email>
      </contact>
      <contact_backup>
        <last_name>Chunyu Yu, MD</last_name>
        <email>yuchunyu@fuwai.com</email>
      </contact_backup>
      <investigator>
        <last_name>Zhe Zheng, M.D., Ph.D.</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Chunyu Yu, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Haojie Li, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Chuxiang Lei, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>left atrial appendage clipping</keyword>
    <keyword>Stroke</keyword>
    <keyword>Oral anticoagulation</keyword>
    <keyword>Atrial Fibrillation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Atrial Fibrillation</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anticoagulants</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06021808
  org study id: 2023-2059
  nct id: NCT06021808
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This trial is designed to examine the hypothesis that thoracoscopic LAA clipping is superior
        to NOACs for stroke, systemic embolism, all-cause mortality, major bleeding events and
        clinically relevant nonmajor bleeding events in AF patients at high risk of embolism
        (CHA2DS2-VASc ≥2 in men and ≥3 in women) that are not undergoing ablation.
  Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia disease, and the incidence
        of AF increases markedly with age and approximately doubles with each decade. According to
        the previous study, the incidence of stroke were five times in patients with AF than those in
        the general population. Systemic oral anticoagulant is a well-established,
        guideline-recommended therapy for the prevention of ischemic stroke in patients with
        nonvalvular AF at high risk of embolism (CHA2DS2-VASc scores ≥2 in men and ≥3 in women), and
        the guidelines recommend that the novel oral anticoagulants (NOACs) be preferred (Class I,
        Level of evidence A). However, a significant proportion of patients with nonvalvular AF have
        difficulties in long-term oral anticoagulant therapy, due to medication adherence and
        contraindications to oral anticoagulants. Also, several randomized controlled trials
        indicated that bleeding risk remained high with novel oral anticoagulants. Therefore, it is
        essential to explore alternative treatment strategies for stroke prevention in patients with
        nonvalvular AF.
  
        It has been reported that the left atrial appendage (LAA) is suspected as a vital source of
        cerebral emboli and may lead to ischemic stroke, removal or closure of the LAA may be an
        alternative to oral anticoagulants. Various surgical or interventional approaches have been
        developed to close or occlude LAA to prevent stroke in AF patients, such as percutaneous LAA
        occlusion, suture ligation, and surgical excision. However, these techniques suffer from
        incomplete LAA closure or the presence of residual blood flow, which can lead to thrombosis
        and stroke. Thoracoscopic LAA clip, on the other hand, cloud block blood flow between the LAA
        and the left atrium (LA), achieving isolation of LAA and preventing thrombi and strokes. A
        previous study has demonstrated a high 95% success rate of LAA clipping without
        operation-related complications, and freedom from stroke was 99.1% at a median follow-up of
        20 months. Therefore, LAA clipping is an effective and durable method in stroke prevention.
        However, currently high-quality RCTs are lacking to support the superiority of LAA clipping
        compared with NOACs in terms of stroke prevention and safety. In this trial, the
        investigators designed a multicenter prospective RCT to compare the efficacy and safety of
        thoracoscopic LAA clipping and NOACs in patients with non-paroxysmal AF.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Single (Outcomes Assessor)
  measure: Rate of composite endpoint
  time frame: At 24-month after intervention
  description: Stroke, systemic embolism, all-cause mortality, major bleeding event, and clinically relevant non-major bleeding event.
  measure: Rate of stroke
  time frame: At 24-month after intervention
  description: Acute episodes of focal or global neurological dysfunction due to cerebral, spinal cord or retinal vascular injury from haemorrhage or infarction. Symptoms or signs must have lasted ≥ 24 hours, or symptoms/signs may have lasted less than 24 hours if demonstrated by CT, MRI, or autopsy.
  measure: Rate of systemic embolism
  time frame: At 24-month after intervention
  description: Confirmed by imaging or angiography
  measure: Rate of all-cause mortality
  time frame: At 24-month after intervention
  description: Deaths from all causes
  measure: Rate of major bleeding event
  time frame: At 24-month after intervention
  description: fatal haemorrhage, and/or
  Symptomatic haemorrhage in a critical area or organ, such as intracranial, intravertebral, intraocular, retroperitoneal, intra-articular or intrapericardial, or intramuscular haemorrhage leading to osteofascial compartment syndrome, and/or 3. haemorrhage that results in a fall in haemoglobin level of 2.0 g/dL or more, or that results in the importation of two or more units of whole blood or red blood cells.
  measure: Rate of clinically relevant non-major bleeding event
  time frame: At 24-month after intervention
  description: Bleeding events that do not meet the criteria for an ISTH major bleeding event but requires hospitalisation or a change in antithrombotic treatment strategy or requires invasive management.
  measure: Rate of surgery-related complications
  time frame: At 24-month after intervention
  description: Incidence of in-hospital death, in-hospital stroke, intermediate small-incision open thoracotomy or median open thoracotomy, and postoperative re-intervention due to hemorrhage, pneumothorax, and pyothorax.
  measure: Rate of minor bleeding events
  time frame: At 24-month after intervention
  description: Bleeding events that do not meet the ISTH criteria for a major bleeding event, do not meet the criteria for a clinically relevant non-major bleeding event, and do not require the subject to seek additional assistance from medical care.
  arm group label: LAA clipping group
  arm group type: Experimental
  description: In this arm, participants are performed thoracoscopic LAA clipping.
  arm group label: NOACs group
  arm group type: Active Comparator
  description: Patients randomized to NOAC therapy will begin long-term oral administration of NOACs immediately after enrollment.
  intervention type: Procedure
  intervention name: Thoracoscopic LAA clipping
  description: The surgeons measured the length of the base of the LAA, an appropriately sized LAA clip is then inserted with the aid of a thoracoscope and placed parallel to the base of the LAA.
  arm group label: LAA clipping group
  intervention type: Drug
  intervention name: Novel oral anticoagulant
  description: For patients with creatinine clearance ≥50 ml/min, oral rivaroxaban 20 mg daily was administered, whereas for patients with creatinine clearance between 30-49 ml/min, oral rivaroxaban 15 mg daily was administered.
  arm group label: NOACs group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Zhe Zheng, MD,PhD
  role: Study Chair
  affiliation: Fuwai Hospital
  last name: Zhe Zheng, MD,PhD
  phone: +86-010-88396051
  email: zhengzhe@fuwai.com
  last name: Chunyu Yu, MD
  email: yuchunyu@fuwai.com
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Atrial Fibrillation
  mesh term: Anticoagulants
  sharing ipd: No