Discontinuation of Anticoagulations After Successful Catheter Ablation of Atrial Fibrillation

NCT ID: NCT06615596

Last Updated: 2024-09-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-31
• Study Completion Date: 2029-12-31

Brief Summary

The DESTINATION Study investigates whether anticoagulation therapy is necessary after successful catheter ablation (CA) for atrial fibrillation (AF). Current guidelines recommend continued anticoagulation based on stroke risk scores, even post-ablation, potentially exposing patients to unnecessary bleeding risks. This international, multicenter, randomized controlled trial aims to compare thromboembolic and bleeding event risks between patients who continue and discontinue anticoagulation after ablation. The study involves 3,160 AF patients, all free of AF recurrence within 6 months to 1 year after ablation. Smart wearable monitors will track recurrence, and patients are followed for 24 months to assess event rates. Findings may reshape anticoagulation guidelines, improving clinical practice for AF patients worldwide.

Detailed Description

This prospective, international, multicenter randomized controlled trial (RCT) investigates the safety and necessity of continuing anticoagulation therapy after successful catheter ablation of atrial fibrillation. The study will enroll 3,160 patients who underwent catheter ablation for AF and achieved no recurrence within 6 months to 1 year post-procedure. Participants will be randomly assigned to either continue or discontinue anticoagulation therapy. Smart wearable devices will monitor AF recurrence every 3 months, detecting both symptomatic and asymptomatic events. The study's primary endpoint is a composite of ischemic stroke, systemic embolism, and major bleeding at a 24-month follow-up. Secondary outcomes include AF recurrence rates, re-ablation needs, and quality of life measures. Participants are monitored through follow-up visits at 3, 6, 12, 18, and 24 months, and data from wearable devices will be transmitted to the research team. This study is significant due to the diversity of the population, with sites in China and the US, allowing for results that are generalizable across ethnic and geographic lines. The trial's findings aim to provide high-quality evidence to inform future guideline recommendations regarding post-ablation anticoagulation therapy, potentially reducing unnecessary bleeding risks and optimizing treatment outcomes. The inclusion of smart wearable monitors enhances the detection of asymptomatic recurrences and provides continuous, reliable data on patient health during the follow-up period.

Conditions

Atrial Fibrillation (AF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

on-OAC

In the cohort assigned to the "on-OAC" arm, which entails the continuation of Oral Anticoagulant (OAC) therapy, patients were prescribed Non-Vitamin K Antagonist Oral Anticoagulants (NOACs), specifically dabigatran, rivaroxaban, or apixaban, for a duration of 24 months following randomization. The dosing regimen was as follows: (1) Standard dosage included rivaroxaban at 20mg daily, apixaban at 5mg twice daily, and dabigatran at 150mg twice daily. (2) Reduced dosage was administered in cases where patients were aged over 75 years, had a body weight less than 50kg, or exhibited creatinine clearance below 50ml/min.

Group Type: ACTIVE_COMPARATOR

Anticoagulant drugs

Intervention Type: DRUG

Participants in the continuation arm will receive oral anticoagulant drugs such as dabigatran, rivaroxaban, apixaban, warfarin, etc. tailored to their specific risk profiles. The discontinuation arm will cease anticoagulation therapy following randomization. Smart wearable devices will monitor for AF recurrence, and patients will be followed for 24 months, with primary endpoints including thromboembolic and bleeding events.

Catheter Ablation

Intervention Type: PROCEDURE

Catheter ablation is a medical procedure used to treat atrial fibrillation (AF) by targeting and destroying small areas of heart tissue that cause irregular heartbeats. Using a specialized catheter, radiofrequency energy, cryotherapy, or pulsed field ablation (PFA) is applied to isolate the pulmonary veins or ablate other specific heart areas. The goal is to restore normal heart rhythm by electrically isolating problematic areas responsible for AF. This FDA-regulated procedure is minimally invasive and requires follow-up monitoring for AF recurrence and other potential complications. No specific ablation technique is mandated, allowing flexibility for operators to choose based on their expertise and center practices. The ablation strategy may include pulmonary vein isolation or additional procedures based on the type of AF. This approach distinguishes the study by providing real-world applicability, reflecting the diversity of ablation methods used in clinical practice.

off-OAC

In the off-OAC, involving the discontinuation of OAC therapy, patients had their OAC treatment terminated post-randomization, and no placebo medication was administered as a substitute.

Group Type: EXPERIMENTAL

discontinue anticoagulation therapy

Intervention Type: BEHAVIORAL

Participants in the discontinuation arm will cease anticoagulation therapy following randomization. Smart wearable devices will monitor for AF recurrence, and patients will be followed for 24 months, with primary endpoints including thromboembolic and bleeding events.

Catheter Ablation

Intervention Type: PROCEDURE

Catheter ablation is a medical procedure used to treat atrial fibrillation (AF) by targeting and destroying small areas of heart tissue that cause irregular heartbeats. Using a specialized catheter, radiofrequency energy, cryotherapy, or pulsed field ablation (PFA) is applied to isolate the pulmonary veins or ablate other specific heart areas. The goal is to restore normal heart rhythm by electrically isolating problematic areas responsible for AF. This FDA-regulated procedure is minimally invasive and requires follow-up monitoring for AF recurrence and other potential complications. No specific ablation technique is mandated, allowing flexibility for operators to choose based on their expertise and center practices. The ablation strategy may include pulmonary vein isolation or additional procedures based on the type of AF. This approach distinguishes the study by providing real-world applicability, reflecting the diversity of ablation methods used in clinical practice.

Interventions

discontinue anticoagulation therapy

Participants in the discontinuation arm will cease anticoagulation therapy following randomization. Smart wearable devices will monitor for AF recurrence, and patients will be followed for 24 months, with primary endpoints including thromboembolic and bleeding events.

Intervention Type: BEHAVIORAL

Anticoagulant drugs

Participants in the continuation arm will receive oral anticoagulant drugs such as dabigatran, rivaroxaban, apixaban, warfarin, etc. tailored to their specific risk profiles. The discontinuation arm will cease anticoagulation therapy following randomization. Smart wearable devices will monitor for AF recurrence, and patients will be followed for 24 months, with primary endpoints including thromboembolic and bleeding events.

Intervention Type: DRUG

Catheter Ablation

Catheter ablation is a medical procedure used to treat atrial fibrillation (AF) by targeting and destroying small areas of heart tissue that cause irregular heartbeats. Using a specialized catheter, radiofrequency energy, cryotherapy, or pulsed field ablation (PFA) is applied to isolate the pulmonary veins or ablate other specific heart areas. The goal is to restore normal heart rhythm by electrically isolating problematic areas responsible for AF. This FDA-regulated procedure is minimally invasive and requires follow-up monitoring for AF recurrence and other potential complications. No specific ablation technique is mandated, allowing flexibility for operators to choose based on their expertise and center practices. The ablation strategy may include pulmonary vein isolation or additional procedures based on the type of AF. This approach distinguishes the study by providing real-world applicability, reflecting the diversity of ablation methods used in clinical practice.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Diagnosed paroxysmal, persistent, or longstanding persistent AF
• Successful procedure (defined as restoration of sinus rhythm after PV isolation for paroxysmal AF, restoration of sinus rhythm after PV isolation and completion of additional ablation for persistent AF, according to 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation) and no recurrence within 3 months of ablation, using a cooled tip RF-, laser- or cryo-balloon-catheter
• No periprocedural complications
• Signed informed consent
• Male with CHA2DS2-VASC score ≥1, female with score ≥2.

Exclusion Criteria

• Valvular AF (moderate- severe mitral insufficiency; relevant mitral stenosis with a mean pressure gradient >5mmHg)
• Reversible AF (e.g. uncontrolled hyperthyroidism)
• Prior AF ablation (including surgical ablation)
• History of left atrial appendage occlusion/ligation/excision
• Concomitant surgical ablation
• Left atrial diameter >50 mm
• Left atrial or LAA thrombus
• Pregnancy/breast feeding
• Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
• Patient has a non-arrhythmic condition necessitating long-term oral anticoagulation (i.e. PE, ventricular thrombus, peripheral thrombosis, etc)
• Recent myocardial infarction, NYHA class IV heart failure, patent foramen ovale, recent trauma or other prothrombotic conditions
• Patient with special risk factors for stroke unrelated to AF, specifically known thrombophilia/ hypercoagulability, uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg within 4 days of enrollment), untreated familial hyperlipidemia, known vascular anomaly (intracranial aneurysm/ arteriovenous malformation or chronic vascular dissection), or known severe carotid disease.
• Patient has bleeding contra-indication to oral anticoagulation (such as bleeding diathesis, hemorrhagic disorder, significant gastrointestinal bleeding within 6 months, intracranial/intraocular/ atraumatic bleeding history, fibrinolysis within 48 hours of enrollment).
• Patient has other contraindication to oral anticoagulation or treatment with antiplatelet agent
• Patient has been on strong CYP3A inducers (such as rifampicin, phenytoin, phenobarbital, or carbamazepine) or strong CYP3A inhibitors (such as ketoconazole or protease inhibitors) within 4 days of enrolment
• Structural congenital heart disease
• Recent stroke or intracranial hemorrhage within 6 months
• Inability to adequately understand nature, significance, implications and risks of study precipitation and to comply with follow-up (i.e. bipolar disorders, severe depression, suicidal tendencies, among others) as judged by the local physician, ongoing drug or alcohol addiction (> 8 drinks/week)
• Patients who are > 85 years of age
• Patients who are critically ill or who have a life expectancy <3 years
• Patient is unable or unwilling to provide informed consent
• Patient is included in another randomized clinical trial or a clinical trial requiring an insurance

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China National Center for Cardiovascular Diseases

OTHER_GOV

Sponsor Role: lead

Responsible Party

Yan Yao, MD,PhD

Director, Arrhythmia Center, Fu Wai Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women Hospital

Boston, Massachusetts, United States

Beijing Anzhen Hospital

Beijing, Beijing Municipality, China

Fuwai Hospital

Beijing, Beijing Municipality, China

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen

Shenzhen, Guangdong, China

Fuwai Central China Cardiovascular Hospital

Zhengzhou, Henan, China

Wuhan Asia Heart Hospital

Wuhan, Hubei, China

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Shanxi Cardiovascular Hospital (Shanxi Cardiovascular Research Institute)

Taiyuan, Shanxi, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Yunnan Fuwai Cardiovascular Hospital

Kunming, Yunnan, China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Countries

United States; China

Central Contacts

Yan Yao, PhD

Role: CONTACT

ianyao@263.net.cn

13901121319

Lingmin Wu, Phd

Role: CONTACT

wulingmin@fuwai.com

Facility Contacts

Paul Zei, PhD

Role: primary

pzei@bwh.harvard.edu

+1 (650) 521-2173

Paul Zei, PhD

Role: backup

Yunlong Wang, PhD

Role: primary

Yunlong76818@126.com

13937193530

Ligang Ding, Phd

Role: primary

dlgang101@163.com

18610561552

Ligang Ding, dlgang101@163.com

Role: backup

Jiangui He, PhD

Role: primary

hejiangui@163.com

18902233622

Yan Yao, Phd

Role: primary

ianyao@263.net.cn

13901121319

Zhongpeng Du, Phd

Role: backup

18819045381

Yan Yao, ianyao@263.net.cn

Role: backup

Xianqing Wang, PhD

Role: primary

13937193530@139.com

13937193530

Jinlin Zhang, PhD

Role: primary

zjl1974@yeah.net

15972226949

Xu Liu, PhD

Role: primary

xkliuxu@126.com

15026921131

Haixiong Wang, PhD

Role: primary

cz1976whx@126.com

15003433600

Hua Fu, PhD

Role: primary

fuhua0108@qq.com

13908042335

Jinrui Guo, Phd

Role: primary

Sailor2k@163.com

17801013903

Chenyang Cheng, PhD

Role: primary

jiangchenyang@hotmail.com

13857190051

Other Identifiers

NCRCSZ-2023-011

Identifier Type: -

Identifier Source: org_study_id