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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 : Not yet recruiting
First Posted : January 30, 2019
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary:

This study is a 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 85 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 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, 120 patients will be included, with an estimated total number of 240 participants in this clinical study. Patients will be followed up for 12 months.

During the follow-up, the events of stroke/TIA, systematic embolism, cardiovascular death, device-related thrombus, major bleedings and hospitalization due to heart failure et al. will be identified and recorded. Patients will be followed-up in the third, sixth, twelfth months for clinical events. Items including 12-leads ECG, 24h Holter ECG, transesophageal echocardiography and transthoracic echocardiography, will be performed and NT-proBNP and inflammatory cytokines will be measured 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.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Termination of aspirin Not Applicable

Detailed Description:

This study is a perspective and 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 240 patients in accordance with the inclusion and exclusion criteria. 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 in accordance with the result of randomization. Participants will be assessed and observed carefully throughout the procedure of the study.
  3. The participants will be followed-up in the third, sixth and twelfth months after randomization for clinical events after the intervention. The main follow-up includes a review of ECG, 24h Holter, echocardiography, transesophageal echocardiography, coronary CT, biomarker (NT-pro-BNP) and inflammatory cytokines, including tumor necrosis factor -alpha, interleukin-6 and monocyte chemoattractant protein 1 (MCP1) et al. 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, and cardiovascular death; the incidences of device-related thrombus, major bleedings, and hospitalization due to heart failure will be recorded. Adverse events during the trial will also be assessed and recorded.
  4. Collect research data and perform the statistical analysis. For Statistical analysis, the sample size calculation is based on the overall incidence of stroke, systemic embolism, and cardiovascular death. The study includes multiple endpoint tests that would use a 5% significance level with a test efficacy of 90%. Assume that 10% of patients have withdrawn from the middle and 10% have lost follow-up. According to the literature and most experts, the total proportion of stroke, systemic embolism and cardiovascular death in patients with atrial fibrillation are 6.4/100 person-years after LAAC. The investigators estimate that terminating the use of aspirin will not influence the incidence of the composite endpoint of stroke, systemic embolism, and cardiovascular death. The rate of the composite endpoint events is 6.4/100 person-years. The preset non-inferiority margin for this study is 1.75. According to the sample size estimation formula, the number of trials should be 240 patients (120 in each group).

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 1 year after completion of the treatment. It is expected that the trial will be completed in a total of 36 months by January 2022.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety of Terminating the Use of Aspirin After Left Atrial Appendage Closure in Patients With Atrial Fibrillation
Estimated Study Start Date : February 1, 2019
Estimated Primary Completion Date : January 30, 2021
Estimated Study Completion Date : January 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Termination of aspirin therapy
After the Left atrial appendage closure (LAAC), patients may need anticoagulation or antiplatelet therapies until the sixth month after the procedure. In this arm, since the sixth month, patients will stop using aspirin for further antiplatelet therapy.
Drug: Termination of aspirin
Terminate use of aspirin in the experimental group and continue to use aspirin in the active comparator group
Other Name: Termination of antiplatelet therapy

No Intervention: Continuance of aspirin therapy
After the Left atrial appendage closure (LAAC), patients may need anticoagulation or antiplatelet therapies until the sixth month after the procedure. In this arm, since the sixth month, patients will continue to use aspirin for further antiplatelet therapy.



Primary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. History of paroxysmal/sustained atrial fibrillation (evidence includes any of the following: Holter or 12-lead ECG recorder to atrial fibrillation);
  2. One or more drug treatments are ineffective or patients unwilling to be treated with long-term drugs;
  3. Unable to tolerate drug treatment or with contraindications
  4. CHA2DS2-VASc score ≥ 2 and/or HAS-BLED score ≥ 3
  5. Provide informed consent to participate in the study, follow-up trials and assessment procedures;
  6. With an age between 18-85 years
  7. Have undergone one-stop treatment of left atrial appendage or left atrial appendage plus radiofrequency ablation in our hospital

Exclusion Criteria:

  1. Combined with coronary heart disease and stroke and need long-term use of aspirin for secondary prevention
  2. There are acute lesions, such as acute phase after myocardial infarction (within 3 months), acute heart attack or 3 months after new cerebral infarction;
  3. Life expectancy is less than 1 year;
  4. Age > 85 years old
  5. With aspirin use contraindications such as active peptic ulcer or other bleeding disorders
  6. Patients with uncontrolled cancer ;
  7. Obvious liver and kidney function, abnormal blood coagulation;
  8. The esophageal echocardiography at the 6th month after surgery indicates that the device-related thrombus or has a residual leakage >5mm
  9. Women who are pregnant, breastfeeding, pregnant, or women of childbearing age who do not have reliable methods of contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03821883


Contacts
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Contact: Zhiquan Wang, Dr. 86 021 25077275 wangzhiquan@xinhuamed.com.cn

Locations
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China, Shanghai
Xinhua Hospital, Shanghai Jiao Tong University School of Medicne Active, not recruiting
Shanghai, Shanghai, China, 200092
Sponsors and Collaborators
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Investigators
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Principal Investigator: Yi-Gang Li, Dr. Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Publications of Results:

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Responsible Party: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT03821883     History of Changes
Other Study ID Numbers: XH-18-017
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Aspirin
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics