Timing of Anticoagulation After Emergency Endovascular Therapy for Acute Ischemic Stroke With Atrial Fibrillation

Official title

Timing of Anticoagulation After Emergency Endovascular Therapy for Acute Ischemic Stroke With Atrial Fibrillation：a Randomised Controlled Trial

Overview

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 after emergency endovascular therapy (EVT).

Detailed description

This is a multicenter, prospective, open-label, randomized controlled trial evaluating the safety and efficacy of different initiation timings of direct oral anticoagulants (DOACs) therapy in patients with acute ischemic stroke related to atrial fibrillation after emergency endovascular therapy (EVT).

Interventions

• Drug Early anticoagulation
  Early initiation of direct oral anticoagulants will be started within four days after symptom onset.
• Drug Delayed anticoagulation
  Delayed initiation of direct oral anticoagulants will be started between 5-14 days after symptom onset.

Primary outcome measures

• Composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, and all-cause death [Time frame: 90 days]

Secondary outcome measures (12)

• Incidence of recurrent ischemic stroke [Time frame: 90 days and 1 year]
• Incidence of venous thromboembolism [Time frame: 90 days]
• Incidence of systemic embolism [Time frame: 90 days]
• Incidence of myocardial infarction [Time frame: 90 days]
• Proportion of Patients Achieving mRS 0-1 [Time frame: 90 days and 1 year]
• Proportion of Patients Achieving mRS 0-2 [Time frame: 90 days and 1 year]
• Length of hospital stay for stroke-related care [Time frame: 90 days]
• Quality of life assessed by EuroQol 5 Dimensions 5 level questionnaire [EQ-5D-5L] [Time frame: 90 days and 1 year]
• Incidence of vascular death [Time frame: 90 days]
• All-cause mortality [Time frame: 90 days and 1 year]
• Incidence of symptomatic intracranial haemorrhage (sICH) [Time frame: 90 days]
• Incidence of major extracranial bleeding [Time frame: 90 days]

Eligibility criteria

Inclusion criteria

• Aged 18 years or over.
• Clinical diagnosis of large vessel occlusion acute ischemic stroke.
• Emergency endovascular treatment was performed within 24 hours of stroke onset.
• Atrial fibrillation (including paroxysmal, persistent or permanent atrial fibrillation), confirmed by at least one of the following:

• 12-lead ECG recording
• Inpatient ECG telemetry
• Prolonged ECG monitoring (e.g. Holter monitor)
• Previously established diagnosis of atrial fibrillation verified by medical records.
• CT or MRI demonstrating one of the following findings:

• No hemorrhagic transformation;
• Hemorrhagic infarction type 1 (HI1), defined as small petechiae along the margins of the infarct (Heidelberg classification);
• Hemorrhagic infarction type 2 (HI2), defined as confluent petechiae within the infarcted area without space-occupying effect (Heidelberg classification).
• Time from stroke onset to randomization was within 72 hours.
• Written informed consent obtained from the patient or a legally authorized representative.

Exclusion criteria

• Atrial fibrillation due to reversible causes (e.g. thyrotoxicosis, pericarditis, recent surgery, or myocardial infarct).
• Contraindication to the use of direct oral anticoagulants (DOACs):

• Known allergy or intolerance to both factor Xa inhibitors and direct thrombin inhibitors;
• Definite indication for vitamin K antagonist (VKA) treatment (e.g. mechanical heart valve, valvular atrial fibrillation);
• 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) ;
• Concomitant use of medications with significant interactions with DOACs, including azole antifungals, HIV protease inhibitors, or strong CYP3A4 inducers;
• Baseline platelet count < 100 x 109/L;
• History of coagulopathy or systemic hemorrhage.
• Prior DOAC use within 48 hours of stroke onset, or recent treatment with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomization.
• Pregnant or breastfeeding women, or positive pregnancy test at admission.
• History of major surgery or severe trauma within 1 month prior to stroke onset.
• History of active bleeding within 1 month prior to stroke onset (e.g. gastrointestinal bleeding, urinary tract bleeding).
• Dual antiplatelet therapy at baseline, or strong likelihood of requiring dual antiplatelet therapy during the trial.
• Evidence of cerebral amyloid angiopathy.
• CT or MRI evidence of non-stroke pathology likely to account for the presenting clinical symptoms (e.g. mass lesion, encephalitis).
• Modified Rankin scale (mRS) score > 1 prior to stroke onset.
• Inability to complete the 90-day follow-up.
• Currently participating in another drug clinical trial.
• Any other reason deemed by the investigator to make the patient unsuitable for participation in the trial.

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 · 40 centers

• Ma'anshan People's Hospital — Ma’anshan
• Aviation General Hospital — Beijing
• Beijing Shijingshan Hospital — Beijing
• Zhangzhou Municipal Hospital of Fujian Province — Zhangzhou
• Heyuan People's Hospital — Heyuan
• Qinzhou First People's Hospital — Qinzhou
• Baoding Sixth Hospital — Baoding
• The First Affiliated Hospital of Harbin Medical University — Harbin
• … and 32 more centers

Identifiers

NCT: NCT07139301 · TIMERS-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗