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Safety of Terminating the Use of Aspirin After Left Atrial Appendage Closure

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ClinicalTrials.gov Identifier: NCT03821883
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Tracking Information
First Submitted Date  ICMJE January 22, 2019
First Posted Date  ICMJE January 30, 2019
Last Update Posted Date August 22, 2019
Actual Study Start Date  ICMJE February 1, 2019
Estimated Primary Completion Date January 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
  • Stroke [ Time Frame: 24 months after the date of randomization. ]
    A stroke is a medical condition in which poor blood flow to the brain results in cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. They result in part of the brain not functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. If symptoms last less than one or two hours it is known as a transient ischemic attack (TIA) or mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Brain computed tomography or MRI may help diagnose stroke.
  • Systemic embolism [ Time Frame: 24 months after the date of randomization. ]
    An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus is usually a blood clot (thrombus). An embolism can cause partial or total blockage of blood flow in the affected vessel. An embolism in which the embolus is a piece of thrombus is called a thromboembolism. An embolism is usually a pathological event, i.e., accompanying illness or injury. Sometimes it is created intentionally for a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Embolism can be classified as to where it enters the circulation either in arteries or in veins. Arterial embolism are those that follow and, if not dissolved on the way, lodge in a more distal part of the systemic circulation.
  • Cardiovascular/unexplained death [ Time Frame: 24 months after the date of randomization. ]
    Cardiovascular deaths refer to deaths due to heart dysfunction, injury of cardiac structure, coronary artery diseases and lethal arrhythmias or sudden death that cannot be explain. Cardiovascular deaths can be diagnosed with clinical symptoms or from the results of diagnostic examinations.
  • Major bleedings [ Time Frame: 24 months after the date of randomization. ]
    Major bleedings refer to the heavy bleedings of the mains organs of the body, usually include intracranial bleeding and gastrointestinal bleeding et al.. Brain computed tomography and gastrointestinal endoscope are the common approaches for diagnosing major bleedings.
  • acute coronary syndrome [ Time Frame: 24 months after the date of randomization. ]
    Acute coronary syndrome (ACS) is a syndrome (set of signs and symptoms) due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is chest pain, often radiating to the left shoulder or angle of the jaw, crushing, central and associated with nausea and sweating. Many people with acute coronary syndromes present with symptoms other than chest pain, particularly, women, older patients, and patients with diabetes mellitus. Acute coronary syndrome is commonly associated with three clinical manifestations, named according to the appearance of the electrocardiogram (ECG): ST elevation myocardial infarction (STEMI, 30%), non-ST elevation myocardial infarction (NSTEMI, 25%), or unstable angina (38%). There can be some variation as to which forms of myocardial infarction (MI) are classified under acute coronary syndrome.
  • Coronary or periphery artery disease requiring revascularization [ Time Frame: 24 months after the date of randomization. ]
    Conronary or periphery artery diseases, regardless stable or not, need revascularization by stent which require long-term aspirin therapy
Original Primary Outcome Measures  ICMJE
 (submitted: January 27, 2019)
  • Stroke [ Time Frame: 12 months after the date of randomization. ]
    A stroke is a medical condition in which poor blood flow to the brain results in cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. They result in part of the brain not functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. If symptoms last less than one or two hours it is known as a transient ischemic attack (TIA) or mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Brain computed tomography or MRI may help diagnose stroke.
  • Systemic embolism [ Time Frame: 12 months after the date of randomization. ]
    An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus is usually a blood clot (thrombus). An embolism can cause partial or total blockage of blood flow in the affected vessel. An embolism in which the embolus is a piece of thrombus is called a thromboembolism. An embolism is usually a pathological event, i.e., accompanying illness or injury. Sometimes it is created intentionally for a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Embolism can be classified as to where it enters the circulation either in arteries or in veins. Arterial embolism are those that follow and, if not dissolved on the way, lodge in a more distal part of the systemic circulation.
  • Cardiovascular/unexplained death [ Time Frame: 12 months after the date of randomization. ]
    Cardiovascular deaths refer to deaths due to heart dysfunction, injury of cardiac structure, coronary artery diseases and lethal arrhythmias or sudden death that cannot be explain. Cardiovascular deaths can be diagnosed with clinical symptoms or from the results of diagnostic examinations.
Change History Complete list of historical versions of study NCT03821883 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
  • Device-related thrombus [ Time Frame: 24 months after the date of randomization. ]
    This refers to the thrombus that is related to the implantation of the device for left atrial appendage closure. Transesophageal echocardiography is effective in identifying and diagnosing device-related thrombus.
  • Minor bleedings [ Time Frame: 24 months after the date of randomization. ]
    Minor bleedings refer to the bleedings acoording to the TIMI cirteria
  • Hospitalization due to heart failure [ Time Frame: 24 months after the date of randomization. ]
    Patients need to receive treatments in hospital because of occurrence of heart failure or deterioration of heart failure.
  • all-cause death [ Time Frame: 24 months after the date of randomization. ]
    any cause of death
Original Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2019)
  • Device-related thrombus [ Time Frame: 12 months after the date of randomization. ]
    This refers to the thrombus that is related to the implantation of the device for left atrial appendage closure. Transesophageal echocardiography is effective in identifying and diagnosing device-related thrombus.
  • Major bleedings [ Time Frame: 12 months after the date of randomization. ]
    Major bleedings refer to the heavy bleedings of the mains organs of the body, usually include intracranial bleeding and gastrointestinal bleeding et al.. Brain computed tomography and gastrointestinal endoscope are the common approaches for diagnosing major bleedings.
  • Hospitalization due to heart failure [ Time Frame: 12 months after the date of randomization. ]
    Patients need to receive treatments in hospital because of occurrence of heart failure or deterioration of heart failure.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of Terminating the Use of Aspirin After Left Atrial Appendage Closure
Official Title  ICMJE Safety of Terminating the Use of Aspirin After Left Atrial Appendage Closure in Patients With Atrial Fibrillation
Brief Summary

This study is a multicenter, prospective, randomized, non-inferiority study aimed at investigating the safety of terminating the use of aspirin since the sixth month after left atrial appendage closure (LAAC).

Patients diagnosed with paroxysmal or persistent atrial fibrillation with an age between 18 and 90 years and have undergone LAAC or LAAC in combination with catheter ablation (CA) will be enrolled in this study. After the procedure of LAAC or LAAC in combination with CA, patients will receive warfarin or novel oral anticoagulants for 45 days (for LAAC alone) or 90 days (for combined procedure of LAAC and CA) and then switch to the dual-antiplatelet therapy with aspirin and clopidogrel until the sixth month. Six months after the procedure, patients will be divided randomly into two groups. In the first group, patients will terminate the use of both aspirin and clopidogrel. In the other group, patients will continue to use aspirin for antiplatelet therapy lifelong. For each group, 560 patients will be included, with an estimated total number of 1120 participants in this clinical study. Patients will be followed up until 24 months after the last enrollment.

During the follow-up, the events of stroke, systemic embolism, major bleeding, cardiovascular/unexplained death, acute coronary syndrome, coronary or periphery artery disease requiring revascularization, as well as all-cause death, device-related thrombus, minor bleeding, rehospitalization due to heart failure will be identified and recorded. Patients will be followed-up in 3, 6, 12 and 24 months for clinical events. Items, including 12-leads ECG, 24h Holter, transesophageal echocardiography and transthoracic echocardiography, will be performed at 12 months. Statistics analysis will be performed to compare the differences between the two groups in the events of primary and secondary endpoints. The investigators hypothesize that terminating the use of aspirin at the sixth month after LAAC will be non-inferior to continuing using aspirin.

Detailed Description

This study is a multicenter, perspective, randomized, non-inferiority clinical trial investigating the safety of terminating the use of aspirin since the sixth month after LAAC in patients with atrial fibrillation. The investigators and sponsors will work together to develop research protocols, case report forms, research medical records, and informed consent in accordance with the Declaration of Helsinki. Research related materials will be reported to the Medical Ethics Committee for review and approval. All included patients will sign the informed consent form and be followed-up regularly for clinical outcomes and adverse events.

This study will be conducted in accordance with the following procedures:

  1. Screen out 1120 patients in accordance with the inclusion and exclusion criteria from mutiple institutions. The screening period begins with the subject signing the informed consent form and until the subject begins receiving an intervention. Usually, the subject's written informed consent must be obtained prior to any trial-related procedures. If the subject has received physical examinations and laboratory tests within 2 weeks prior to screening after admission, the participants may also sign informed consent and use the results as screening data. After obtaining informed consent, the subject's basic information is recorded in the "subject screening form". The following screening assessments should be made: demographic data, medical history, physical examination, vital signs data, the height and body weight, laboratory parameters, ECG examination, assessment for medication and evaluation for inclusion/exclusion criteria.
  2. After enrollment, participants will be randomly divided into two groups through a computer-based randomization program. Then the patients will either terminate the use of aspirin or continue the use of aspirin 100 mg per day in accordance with the result of randomization. Participants will be assessed and observed carefully throughout the procedure of the study.
  3. After randomization, the participants will be followed-up in 3, 6, 12 and 24 months and every 12 months thereafter until the 24 months after the last enrollment. The main follow-up includes a review of ECG, 24h Holter, echocardiography, transesophageal echocardiography, coronary CT, biomarker such as NT-pro-BNP and also brain CT or MRI if necessary, at the 12 months after randomization. Participants' medication and symptoms will also be observed and recorded. The incidences of stroke, systemic embolism, major bleeding, cardiovascular/unexplained death, acute coronary syndrome, coronary or periphery artery disease requiring revascularization, as well as all-cause death, device-related thrombus, minor bleeding, rehospitalization due to heart failure will be identified and recorded.
  4. Collect research data and perform the statistical analysis. the sample size calculation is based on the overall incidence of composite endpoint of stroke, systemic embolism, major bleeding, cardiovascular or unexplained death, acute coronary syndrome, coronary or periphery artery disease requiring revascularization. We adopt a 5% significance level with a test efficacy of 90%. According to the literature and most experts, the incidence of the primary endpoint is about 7.0/100 person-years after LAAC. The preset non-inferiority margin for this study is 1.5. In order to achieve the non-inferiority, 191 events are expected to be observed. We plan to follow the patients until 2 years after the last enrollment. According to the sample size estimation formula, the number of trials should be 1012 patients (506 in each group). Assuming 10% withdrawn or lost rate, 1120 patients (560 per arm) is needed.

The overall timing of the trial: patients' enrollment and treatment will be completed from February 2019 to January 2021. The last participants will be followed-up for 2 year after completion of the treatment. It is expected that the trial will be completed by January 2023.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Atrial Fibrillation
  • Stroke
  • Left Atrial Appendage Thrombosis
Intervention  ICMJE Drug: Termination of aspirin
Discontinuation of aspirin therapy in the experimental group and continuance of aspirin therapy in the active comparator group
Other Name: Termination of antiplatelet therapy
Study Arms  ICMJE
  • Experimental: Termination of aspirin therapy
    Six months after the Left atrial appendage closure (LAAC), patients will stop using aspirin.
    Intervention: Drug: Termination of aspirin
  • No Intervention: Continuance of aspirin therapy
    Six months after the Left atrial appendage closure (LAAC), patients will continue to use aspirin 100 mg per day for at least 2 years.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 20, 2019)
1120
Original Estimated Enrollment  ICMJE
 (submitted: January 27, 2019)
240
Estimated Study Completion Date  ICMJE January 30, 2023
Estimated Primary Completion Date January 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Including criteria:

History of paroxysmal/persistent atrial fibrillation (evidence includes any of the following: Holter or 12-lead ECG recorder to atrial fibrillation); One or more drug treatments are ineffective or unwilling to be treated with long-term anticoagulants; Unable to tolerate anticoagulation drug treatment or with contraindications Provide informed consent to participate in the study, follow-up trials and assessment procedures; With an age between 18-90 years; Underwent left atrial appendage or left atrial appendage plus radiofrequency ablation in our hospital.

Exclusion Criteria:

Comorbid with recent coronary heart disease and stroke and need long-term use of aspirin for secondary prevention There are acute lesions, such as acute phase after myocardial infarction (within 3 months), acute heart attack or 3 months after new cerebral infarction; Life expectancy is less than 1 year; Age > 90 years old; With aspirin use contraindications such as active peptic ulcer or other bleeding disorders; Patients with uncontrolled cancer; Obvious liver and kidney function, abnormal blood coagulation; The oesophageal echocardiography at the 6th month after surgery indicates that the device-related thrombus or has a residual leakage >5mm; Women who are pregnant, breastfeeding, pregnant, or women of childbearing age who do not have reliable methods of contraception.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mu Chen, Dr. 86 021 25077275 chenmu@xinhuamed.com.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03821883
Other Study ID Numbers  ICMJE XH-18-017
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Study Sponsor  ICMJE Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yi-Gang Li, Dr. Xinhua hospital, School of Medicine, Shanghai Jiao Tong University
PRS Account Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP