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

Overview

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.

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.

Interventions

• 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 isth
• Drug Usual Care
  Patients received standard medical therapy without anticoagulation.

Primary outcome measures

• Composite of All-Cause Mortality, All-Cause Stroke, and Systemic Embolism [Time frame: 48 months]

Secondary outcome measures (9)

• Stroke and Systemic Embolism [Time frame: 48 months]
• Cardiovascular death [Time frame: 48 months]
• Ischemic Stroke [Time frame: 48 months]
• Intracranial Hemorrhage [Time frame: 48 months]
• ISTH Major Bleeding [Time frame: 48 months]
• Clinically relevant non-major bleeding [Time frame: 48 months]
• Change in health-related quality of life assessed by the EQ-5D-5L questionnaire [Time frame: 48 months]
• Change in cognitive function assessed by the Mini-Mental State Examination (MMSE) [Time frame: 48 months]
• modified Rankin Scale score [Time frame: 48 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 7 centers

• The First Affiliated Hospital of Anhui Medical University — Hefei
• Beijing Anzhen Hospital, Capital Medical University — Beijing
• Xiamen Cadiovascular Hospital — Xiamen
• The First Affiliated Hospital of Harbin Medical University — Harbin
• The Second Affiliated Hospital of Harbin Medical University — Harbin
• The First Hospital of Jilin University — Changchun
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi'an

Identifiers

NCT: NCT07316270 · KS2025246

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗