Discontinuation of Anticoagulations After Successful Catheter Ablation of Atrial Fibrillation

NCT06615596 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: NCRCSZ-2023-011
• Study Type: interventional
• Target: 3,160
• Locations: 2 countries
• Sites: 12

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.

Conditions

Atrial Fibrillation (AF)

Keywords

Atrial Fibrillation; Catheter Ablation; Anticoagulation Discontinuation; Post-Ablation Monitoring; Randomized Controlled Trial; Thromboembolic Risk; Smart Wearable Devices; AF Recurrence Detection

Outcome Measures

Primary Outcomes (1)

• Composite outcome consisting of thromboembolic events and clinically significant bleeding events

  The primary endpoint of this study comprises a composite outcome consisting of thromboembolic events and clinically significant bleeding events. Specifically, it encompasses the following components: 1. Incidence of ischemic stroke and systemic thromboembolism within the 2-year post-ablation period in each respective study group. 2. Incidence of clinically significant bleeding within the 2-year post-ablation period in each respective study group. Unit of Measure: Number of events (strokes, systemic embolism, major bleeding episodes).

  24 month

Secondary Outcomes (6)

• AF Recurrence Rate

  24 month

• Repeat Ablation Proportion

  24 month

• Thromboembolic/Bleeding Event Rates after repeat procedure

  24 month

• Thromboembolic/Bleeding Event Rates after recurrence in off-OAC

  24 month

• Major Adverse Cardiovascular Events (MACE)

  24 month

Study Arms (2)

on-OAC

ACTIVE COMPARATOR

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.

Drug: Anticoagulant drugs; Procedure: Catheter Ablation

off-OAC

EXPERIMENTAL

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.

Behavioral: discontinue anticoagulation therapy; Procedure: Catheter Ablation

Interventions

discontinue anticoagulation therapy 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.

off-OAC

Anticoagulant drugs 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.

on-OAC

Catheter Ablation 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; on-OAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• China National Center for Cardiovascular Diseases: lead

Study Sites (12)

Brigham and Women Hospital

Boston, Massachusetts, 02115, United States

Location

Beijing Anzhen Hospital

Beijing, Beijing Municipality, 100011, China

Location

Fuwai Hospital

Beijing, Beijing Municipality, 100037, China

Location

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Location

Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen

Shenzhen, Guangdong, China

Location

Fuwai Central China Cardiovascular Hospital

Zhengzhou, Henan, China

Location

Wuhan Asia Heart Hospital

Wuhan, Hubei, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Location

Shanxi Cardiovascular Hospital (Shanxi Cardiovascular Research Institute)

Taiyuan, Shanxi, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

Yunnan Fuwai Cardiovascular Hospital

Kunming, Yunnan, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Anticoagulants; Catheter Ablation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Radiofrequency Ablation; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Central Study Contacts

Yan Yao, PhD

CONTACT

13901121319; ianyao@263.net.cn

Lingmin Wu, Phd

CONTACT

wulingmin@fuwai.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Arrhythmia Center, Fu Wai Hospital

Model Details: The intervention in this study involves two arms: patients either continue or discontinue anticoagulation therapy after successful catheter ablation for atrial fibrillation (AF). Participants in the continuation arm will receive non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban, etc or warfarin 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.

Study Record Dates

• First Submitted: September 22, 2024
• First Posted: September 26, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CN (11)