AF - Atrial Fibrillation, Intracranial Hemorrhage, Spontaneous
Conditions
Brief summary
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
PROCEDURECatheter 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.
DRUGUsual Care
Patients received standard medical therapy without anticoagulation.
Sponsors
Beijing Anzhen Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite of All-Cause Mortality, All-Cause Stroke, and Systemic Embolism | 48 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stroke and Systemic Embolism | 48 months | — |
| Cardiovascular death | 48 months | — |
| Ischemic Stroke | 48 months | — |
| Intracranial Hemorrhage | 48 months | — |
| ISTH Major Bleeding | 48 months | — |
| Clinically relevant non-major bleeding | 48 months | — |
| Change in health-related quality of life assessed by the EQ-5D-5L questionnaire | 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. |
| Change in cognitive function assessed by the Mini-Mental State Examination (MMSE) | 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. |
| modified Rankin Scale score | 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. |
Countries
China
Contacts
CONTACTLiu He
PRINCIPAL_INVESTIGATORYan Wang
Xiamen Cardiovascular Hospital, Xiamen University
PRINCIPAL_INVESTIGATORCaihua Sang
Beijing Anzhen Hospital
PRINCIPAL_INVESTIGATORChangsheng Ma
Beijing Anzhen Hospital
Outcome results
None listed