Aspirin Discontinuation After Left Atrial Appendage Occlusion in Atrial Fibrillation

Stroke Clinical Trial

— ASPIRIN-LAAO  

Official title:

Aspirin Discontinuation After Left Atrial Appendage Occlusion in Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03821883
• Other study ID #: XH-18-017
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: December 1, 2024

Study information

• Verified date: June 2021
• Source: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: Mu Chen, Dr.
• Phone: 86 021 25077275
• Email: chenmu[@]xinhuamed.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ASPIRIN LAAO trial is a prospective, multi-center, randomized, double blinded, placebo-controlled study aiming at investigating the safety of terminating the use of aspirin after left atrial appendage occlusion (LAAO).

Patients diagnosed with atrial fibrillation and have undergone LAAO will be enrolled in this study. Randomization will be performed at 6 months post-implant. The randomization program electronically assigns the patient 1:1 to either the Aspirin group or the control group. Study patients assigned to Aspirin group will receive enteric coated aspirin (100 mg/day). The control group receives placebo. After the randomization, subjects of both groups will have follow-up visits at 6 and 12 months and then every 12 months until 24 months after the last patient recruitment. 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.

The primary endpoint is a composite consisting of stroke, systemic embolism, cardiovascular or unexplainable death, acute coronary syndrome, coronary artery disease or periphery vascular disease requiring revascularization and major bleeding. The secondary endpoints are all-cause death, device related thrombus, minor bleeding and rehospitalization due to heart failure.

Description:

The ASPIRIN LAAO trial is a prospective, multi-center, randomized, double blinded, placebo-controlled study aiming at investigating the safety of terminating the use of aspirin since the sixth month after LAAO.

Patients diagnosed with paroxysmal or persistent atrial fibrillation with an age between 18 and 90 years and have undergone LAAO will be enrolled in this study. Randomization will be performed at 6 months post-implant. The randomization program electronically assigns the patient 1:1 to either the Aspirin group or the control group. Study patients assigned to Aspirin group will receive enteric coated aspirin (100 mg/day). The control group receives placebo. After the randomization, subjects of both groups will have follow-up visits at 6 and 12 months and then every 12 months until 24 months after the last patient recruitment. 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.

The primary endpoint is a composite consisting of stroke, systemic embolism, cardiovascular or unexplainable death, acute coronary syndrome, coronary artery disease or periphery vascular disease requiring revascularization and major bleeding. The secondary endpoints are all-cause death, device related thrombus, minor bleeding and rehospitalization due to heart failure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1120
• Est. completion date: December 1, 2024
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 90 years

• Paroxysmal, persistent, long-standing persistent or permanent nonvalvular AF

• Have already had a Watchman LAAO device implanted 6 months ago

Exclusion Criteria:

Clinical Exclusion Criteria

• Long-term aspirin therapy required

• Including coronary artery disease, symptomatic carotid disease, prior myocardial infarction, strokes or systemic embolism, etc

• Contraindicated for aspirin therapy

• Including active peptic ulcer, thrombocytopenia or anemia, etc.

• Uncontrolled malignant tumor

• Abnormal liver, renal or coagulation function

• Pregnant or pregnancy is planned during the course of the investigation

• Terminal illness with life expectancy <1 year

• Enrolled in another IDE or IND investigation of a cardiovascular device or an investigational drug

TEE Exclusion Criteria*

• Peri-device leak >5mm

• Device-related thrombus

• Other intracardiac thrombus

Related Conditions & MeSH terms

• Atrial Fibrillation
• Bleeding
• Stroke

Intervention

Drug:
• Aspirin Tablet
Aspirin 100mg qd
• Placebo
Placebo qd

Locations

Country	Name	City	State
China	Xinhua Hospital, School of Medicne, Shanghai Jiao Tong University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

References & Publications (14)

ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Pe — View Citation

Boersma LV, Ince H, Kische S, Pokushalov E, Schmitz T, Schmidt B, Gori T, Meincke F, Protopopov AV, Betts T, Foley D, Sievert H, Mazzone P, De Potter T, Vireca E, Stein K, Bergmann MW; EWOLUTION Investigators. Efficacy and safety of left atrial appendage — View Citation

Boersma LV, Schmidt B, Betts TR, Sievert H, Tamburino C, Teiger E, Pokushalov E, Kische S, Schmitz T, Stein KM, Bergmann MW; EWOLUTION investigators. Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural out — View Citation

Bösche LI, Afshari F, Schöne D, Ewers A, Mügge A, Gotzmann M. Initial Experience With Novel Oral Anticoagulants During the First 45 Days After Left Atrial Appendage Closure With the Watchman Device. Clin Cardiol. 2015 Dec;38(12):720-4. doi: 10.1002/clc.22 — View Citation

Chen S, Weise FK, Chun KRJ, Schmidt B. Antithrombotic strategies after interventional left atrial appendage closure: an update. Expert Rev Cardiovasc Ther. 2018 Sep;16(9):675-678. doi: 10.1080/14779072.2018.1510316. Epub 2018 Aug 29. Review. — View Citation

Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, Howard G, Pearson TA, Rothwell PM, Ruilope LM, Tendera M, Tognoni G; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate ris — View Citation

Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL — View Citation

Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med. 2003 Sep 11;349(11):1019-26. — View Citation

Mac Grory B, Chang A, Atalay MK, Yaghi S. Left Atrial Appendage Thrombus and Embolic Stroke. Stroke. 2018 Sep;49(9):e286-e289. doi: 10.1161/STROKEAHA.118.022674. — View Citation

McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, Shah RC, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Johnston CI, Ryan J, Radzis — View Citation

Piccini JP, Sievert H, Patel MR. Left atrial appendage occlusion: rationale, evidence, devices, and patient selection. Eur Heart J. 2017 Mar 21;38(12):869-876. doi: 10.1093/eurheartj/ehw330. Review. — View Citation

Reddy VY, Doshi SK, Kar S, Gibson DN, Price MJ, Huber K, Horton RP, Buchbinder M, Neuzil P, Gordon NT, Holmes DR Jr; PREVAIL and PROTECT AF Investigators. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials. J Am Co — View Citation

Reddy VY, Möbius-Winkler S, Miller MA, Neuzil P, Schuler G, Wiebe J, Sick P, Sievert H. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With — View Citation

Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, Huber K, Whisenant B, Kar S, Swarup V, Gordon N, Holmes D; PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with stroke	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.	24 months after the date of randomization.
Primary	Number of participants with systemic embolism	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.	24 months after the date of randomization.
Primary	Number of participants with cardiovascular/unexplained death	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.	24 months after the date of randomization.
Primary	Number of participants with major bleedings	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.	24 months after the date of randomization.
Primary	Number of participants with acute coronary syndrome	Acute coronary syndrome 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.	24 months after the date of randomization.
Primary	Number of participants with coronary or periphery artery disease requiring revascularization	Conronary or periphery artery diseases, regardless stable or not, need revascularization by stent which require long-term aspirin therapy	24 months after the date of randomization.
Secondary	Number of participants with device-related thrombus	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.	24 months after the date of randomization.
Secondary	Number of participants with minor bleedings	Minor bleedings refer to the bleedings acoording to the TIMI cirteria	24 months after the date of randomization.
Secondary	Number of Participants with hospitalization due to heart failure	Patients need to receive treatments in hospital because of occurrence of heart failure or deterioration of heart failure.	24 months after the date of randomization.
Secondary	Number of participants with all-cause death	any cause of death	24 months after the date of randomization.