Early anticoagulation: Early initiation of direct oral anticoagulants will be started within 4 weeks after symptom onset.
Delayed anticoagulation: Delayed initiation of direct oral anticoagulants will be started between 4-8 weeks after symptom onset.
Study summary
This study evaluates the safety and efficacy of early versus delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischemic stroke related to atrial fibrillation who develop hemorrhagic transformation after endovascular treatment.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Aged 18 years or over.
2. Clinical diagnosis of large vessel occlusion acute ischemic stroke.
3. Emergency endovascular treatment was performed within 24 hours of stroke onset.
4. Atrial fibrillation (including paroxysmal, persistent or permanent atrial fibrillation), confirmed by at least one of the following:
1. 12-lead ECG recording;
2. Inpatient ECG telemetry;
3. Prolonged ECG monitoring (e.g. Holter monitor);
4. Previously established diagnosis of atrial fibrillation verified by medical records.
5. CT or MRI demonstrating one of the following findings:
1. Parenchymatous hematoma type 1: defined as hematoma occupying less than 30% of the infarcted tissue, no substantive mass effect (Heidelberg classification);
2. Parenchymatous hematoma type 2: defined as heamtoma occupying 30% or more of the infarcted tissue, with obvious mass effect (Heidelberg classification);
3. Intracerebral hemorrhage outside the infarcted brain tissue or intracranial-extracerebral hemorrhage (Heidelberg classification).
6. Time from stroke onset to randomization ranged from 7 days to 4 weeks.
7. Written informed consent obtained from the patient or a legally authorized representative.
Exclusion Criteria:
1. Atrial fibrillation due to reversible causes (e.g. thyrotoxicosis, pericarditis, recent surgery, or myocardial infarct).
2. Contraindication to the use of direct oral anticoagulants (DOACs):
1. Known allergy or intolerance to both factor Xa inhibitors and direct thrombin inhibitors;
2. Definite indication for vitamin K antagonist (VKA) treatment (e.g. mechanical heart valve, valvular atrial fibrillation);
3. Severe renal impairment (defined as creatinine exceeding 1.5 times of the upper limit of normal range) and significant hepatic dysfunction (defined as ALT or AST \> twice the upper limit of normal range) ;
4. Concomitant use of medications with significant interactions with DOACs, including azole antifungals, HIV protease inhibitors, or strong CYP3A4 inducers;
5. Baseline platelet count \< 100 x 109/L;
6. History of coagulopathy or systemic hemorrhage.
3. Prior DOAC use within 48 hours of stroke onset, or recent treatment with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomization.
4. Pregnant or breastfeeding women, or positive pregnancy test at admission.
5. History of major surgery or severe trauma within 1 month prior to stroke onset.
6. History of active bleeding within 1 month prior to stroke onset (e.g. gastrointestinal bleeding, urinary tract bleeding).
7. Dual antiplatelet therapy at baseline, or strong likelihood of requiring dual antiplatelet therapy during the trial.
8. Evidence of cerebral amyloid angiopathy.
9. CT or MRI evidence of non-stroke pathology likely to account for the presenting clinical symptoms (e.g. mass lesion, encephalitis).
10. Modified Rankin scale (mRS) score \> 1 prior to stroke onset.
11. Inability to complete the 90-day follow-up.
12. Currently participating in another drug clinical trial.
13. Any other reason deemed by the investigator to make the patient unsuitable for participation in the trial.
Primary outcome measure(s)
Composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, and all-cause death — 90 days
Trial sites (37)
Facility
City
Region
Status
Ma'anshan People's Hospital
Ma’anshan
Anhui
Recruiting
Xuanwu Hospital
Beijing
Beijing Municipality
Recruiting
Aviation General Hospital
Beijing
Beijing Municipality
Recruiting
Beijing Shijingshan Hospital
Beijing
Beijing Municipality
Recruiting
Zhangzhou Municipal Hospital of Fujian Province
Zhangzhou
Fujian
Recruiting
Heyuan People's Hospital
Heyuan
Guangdong
Recruiting
Qinzhou First People's Hospital
Qinzhou
Guangxi
Recruiting
Baoding Sixth Hospital
Baoding
Hebei
Recruiting
The First Affiliated Hospital of Harbin Medical University
Harbin
Heilongjiang
Recruiting
The Hongda Hospital of Jiamusi University
Jiamusi
Heilongjiang
Recruiting
Fangcheng County People's Hospital
Nanyang
Henan
Recruiting
Nanyang Central Hospital
Nanyang
Henan
Recruiting
Lushan County People's Hospital
Pingdingshan
Henan
Recruiting
Xinyang Central Hospital
Xinyang
Henan
Recruiting
Queshan County People's Hospital
Zhumadian
Henan
Recruiting
Tianyou Hospital, Wuhan University of Science and Technology
Wuhan
Hubei
Recruiting
Northern Jiangsu People's Hospital
Yangzhou
Jiangsu
Recruiting
Yingkou Central Hospital
Yingkou
Liaoning
Recruiting
Ordos Central Hospital,
Ordos
Neimenggu
Recruiting
Feicheng Hospital Of Shandong Yiyang Health Group
Feicheng
Shandong
Recruiting
Jinan Zhangqiu District People's Hospital
Jinan
Shandong
Recruiting
Qilu Hospital of Shandong University
Jinan
Shandong
Recruiting
Laizhou City People's Hospital,
Laizhou
Shandong
Recruiting
Linyi People's Hospital
Linyi
Shandong
Recruiting
Linshu County People's Hospital
Lishui
Shandong
Recruiting
Yantai Yeda Hospital
Yantai
Shandong
Recruiting
Guoyao Northern Hospital (Baotou)
Baotou
Shanxi
Recruiting
ShanXi Cardiovascular Hospital
Taiyuan
Shanxi
Recruiting
The Second Affiliated Hospital of Kunming Medical University
Kunming
Yunnan
Recruiting
Guoluo Prefecture People's Hospital
Guoluo
China
Recruiting
Huanghua Municipal People's Hospital
Huanghua
China
Recruiting
First Affiliated Hospital of Henan Polytechnic University
Jiaozuo
China
Recruiting
Ningjin County People's Hospital
Ningjin
China
Recruiting
Ren Shou County People's Hospital
Renshou
China
Recruiting
Daliuta Experimental District People's Hospital of Shenmu City
Shenmu
China
Recruiting
Xiuyan Central Hospital
Xiuyan
China
Recruiting
The Affiliated Hospital of Xuzhou Medical University
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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