SAfety and eFfectiveness of cathetER Ablation for Atrial Fibrillation With Intracranial Hemorrhage (SAFER-AF)

August 5, 2026 updated by: Beijing Anzhen Hospital
SAFER-AF is an investigator-initiated, multicenter, open-label, parallel-group trial comparing catheter ablation versus usual care in patients with atrial fibrillation and intracranial hemorrhage.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Atrial fibrillation (AF) increases the risk of stroke, heart failure, and mortality. Oral anticoagulation is the standard treatment for preventing thromboembolism, but it also raises the risk of bleeding. About 20-25% of patients with intracranial hemorrhage have AF. Previous randomized trials indicate that restarting anticoagulation may prevent ischemic stroke, but increase risk of recurrent intracranial hemorrhage. Catheter ablation is the first-line rhythm control strategy that reduce thromboembolic risk by maintaining sinus rhythm and potentially reducing the need for long-term anticoagulation. Pulsed field ablation (PFA) uses electroporation to ablate the myocardium by electroporation with high tissue specificity and may shorten the required anticoagulation period.

The SAFER-AF trial is a prospective, multicenter, open-label randomized controlled trial enrolling 646 AF patients with previous spontaneous intracranial hemorrhage, investigating whether catheter ablation provides superior long-term net clinical benefit compared with usual care. Participants will be randomized 1:1 to catheter ablation versus usual care, with a minimum follow-up of 2 years. Patients in catheter ablation group will undergo PFA, followed by low-dose direct oral anticoagulants for 1 month. The primary endpoint is the composite of all-cause mortality, all-cause stroke (ischemic or hemorrhagic), and systemic embolism. SAFER-AF aims to define a safer, individualized therapeutic pathway balancing ischemic protection and hemorrhagic risk, ultimately improving survival and long-term outcomes for AF patients with intracranial hemorrhage.

Study Type

Interventional

Enrollment (Estimated)

646

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230022
        • Not yet recruiting
        • The First Affiliated Hospital of Anhui Medical University
        • Contact:
        • Principal Investigator:
          • Ronghui Yu, MD
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100029
        • Recruiting
        • Beijing AnZhen Hospital, Capital Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Caihua Sang, MD
        • Principal Investigator:
          • Changsheng Ma, MD
    • Fujian
      • Xiamen, Fujian, China
        • Recruiting
        • Xiamen Cadiovascular Hospital
        • Principal Investigator:
          • Yan Wang, MD
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150001
        • Not yet recruiting
        • The First Affiliated Hospital of Harbin Medical University
        • Contact:
        • Principal Investigator:
          • Yue Li, MD
      • Harbin, Heilongjiang, China
        • Not yet recruiting
        • The Second Affiliated Hospital of Harbin Medical University
        • Principal Investigator:
          • Bo Yu, MD
        • Contact:
    • Jilin
      • Changchun, Jilin, China
        • Not yet recruiting
        • The First Hospital of Jilin University
        • Contact:
        • Principal Investigator:
          • Qian Tong, MD
    • Shaanxi
      • Xi'an, Shaanxi, China
        • Not yet recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Principal Investigator:
          • Zuyi Yuan, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Between 14 Days and 12 Months After Spontaneous Intracranial Hemorrhage (intraparenchymal or intraventricular hemorrhage, and subdural hematoma)
  3. Able to Access Intracranial Hemorrhage Imaging Data
  4. ECG indicating the presence of atrial fibrillation
  5. CHA₂DS₂-VA Score ≥ 2
  6. Willing to undergo randomization and able to complete follow-up as required

Exclusion Criteria:

  1. Atrial fibrillation secondary to clearly reversible causes (e.g., hyperthyroidism, hypokalemia, etc.)
  2. Fully dependent (modified Rankin Scale [mRS] score > 4)
  3. Uncontrolled hypertension (systolic blood pressure > 160 mmHg)
  4. Presence of uncontrolled active bleeding
  5. Presence of active infection requiring antibiotic treatment
  6. End-stage renal failure or receiving dialysis treatment
  7. Presence of liver failure
  8. Untreated coronary artery disease with indication for revascularization
  9. Presence of intracardiac masses, thrombi, etc., as evaluated by transthoracic echocardiography or transesophageal echocardiography
  10. Expected life expectancy < 1 year (e.g., advanced malignant tumors, etc.)
  11. Pregnant, lactating, or women planning to become pregnant
  12. Presence of psychological or psychiatric disorders that prevent understanding or cooperation with the study
  13. Other conditions deemed unsuitable for participation in the study by the investigators

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Usual care Group
Drug: Usual Care
Patients received standard medical therapy without anticoagulation.
Experimental: Catheter Ablation Group
Procedure: Catheter Ablation
For patients in the catheter ablation group, low-dose anticoagulation for 1 month after pulsed field ablation is recommended. Suggested regimens include rivaroxaban 10-15 mg once daily, dabigatran 110 mg twice daily, or edoxaban 30 mg once daily. For patients with paroxysmal atrial fibrillation (AF), an ablation strategy based on bilateral pulmonary vein isolation (PVI) is adopted. For patients with persistent AF, PVI plus ethanol infusion of the vein of Marshall and linear ablation (mitral isthmus, cavotricuspid isthmus, and left atrial roof) strategy is recommended. Other additional ablation strategies are determined by the operator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite of All-Cause Mortality, All-Cause Stroke, and Systemic Embolism
Time Frame: 48 months
48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular death
Time Frame: 48 months
48 months
Stroke and Systemic Embolism
Time Frame: 48 months
48 months
Ischemic Stroke
Time Frame: 48 months
48 months
ISTH Major Bleeding
Time Frame: 48 months
48 months
Change in health-related quality of life assessed by the EQ-5D-5L questionnaire
Time Frame: 48 months
The EQ-5D-5L (EuroQol five-dimension, five-level) questionnaire is a standardized, generic measure of health-related quality of life. It consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five levels of severity. Health states are converted into a single index value using a country-specific value set, with higher index values indicating better health-related quality of life.
48 months
Change in cognitive function assessed by the Mini-Mental State Examination (MMSE)
Time Frame: 48 months
The Mini-Mental State Examination is a 30-point questionnaire used to assess global cognitive function. Scores range from 0 to 30, with higher scores indicating better cognitive function.
48 months
Intracranial Hemorrhage
Time Frame: 48 months
48 months
Clinically relevant non-major bleeding
Time Frame: 48 months
48 months
modified Rankin Scale score
Time Frame: 48 months
The modified Rankin Scale (mRS) is a widely used tool for assessing functional disability and dependence in patients with stroke or other neurological disorders. Scores range from 0 to 6, with 0 indicating no symptoms, 5 indicating severe disability requiring constant care, and 6 indicating death. A higher score represents a poorer functional outcome.
48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Anzhen Hospital

Investigators

  • Principal Investigator: Changsheng Ma, Beijing Anzhen Hospital
  • Principal Investigator: Caihua Sang, Beijing Anzhen Hospital
  • Principal Investigator: Yan Wang, Xiamen Cardiovascular Hospital, Xiamen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 6, 2026

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

December 15, 2025

First Submitted That Met QC Criteria

December 30, 2025

First Posted (Actual)

January 5, 2026

Study Record Updates

Last Update Posted (Actual)

August 7, 2026

Last Update Submitted That Met QC Criteria

August 5, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KS2025246

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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