Rivaroxaban Acute Stroke Safety Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Symptomatic Hemorrhagic Transformation Rate
研究概览
简要总结
Atrial fibrillation is a common cardiac arrhythmia and a major risk for ischemic stroke. Furthermore the risk of stroke is higher in the first month after transient ischemic attack (TIA)/stroke. Rivaroxaban has been approved by Health Canada over period of last two years for prevention of stroke and have been found equally effective as oral Vitamin K antagonist. The foremost benefits of NOAC are reduced intracranial bleeding risk and does not require coagulation monitoring.
Optimal timing of anticoagulation after TIA/stroke in patients with known non-valvular atrial fibrillation is not known. The practice is variable and opinion based. The bias for many stroke physicians and neurologists is to start later (after 1-2weeks) to prevent hemorrhagic transformation thus possibly exposing the patients to an increased risk of recurrence. The product monograph for the drug suggest to wait for variable of 3 to 14 days before starting the NOAC (Waiting period:14 days for dabigatran and rivaroxaban, 7 days for Apixaban after ischemic stroke and three days after TIA for rivaroxaban). The times have been chosen arbitrary.
The investigators aim to study incidence of symptomatic hemorrhage in patients with non-valvular atrial fibrillation who are initiated with new oral anticoagulants early after TIA and stroke.
详细描述
Background:
It is clearly established that patients with atrial fibrillation who have suffered a stroke/TIA are at high risk for recurrence and require long-term anticoagulation. What is unknown is the optimal timing of anticoagulation after an ischemic stroke has occurred. Following cardioembolic stroke, atrial fibrillation patients are at risk for early recurrent thrombo-embolism. Estimates of the rate of recurrent stroke in this setting vary widely. Previous studies have indicated new ischemic strokes occur at rates anywhere from 3% to 20% within two weeks of the index event. This is the primary rationale for early anticoagulation after cardioembolic stroke. There is some evidence that early anticoagulation is associated with improved outcomes after ischemic stroke. Indeed, it has been shown that early heparin use does reduce recurrent ischemic stroke risk by 2.1%, but this is offset by a 1.7% increase in the rate of HT. Studies of low molecular weight and unfractionated heparin use in acute stroke have generally indicated these agents are associated with moderately increased risk of HT. There are currently no data indicating the frequency of HT associated with early warfarin treatment, without heparin bridging.
Based on the above evidence, current best practice guidelines recommend against urgent anticoagulation in patients with moderate to severe ischemic stroke, however, due to the elevated risk of hemorrhagic transformation (HT) immediately after stroke. A specific time point at which to begin anticoagulation is not recommended in guideline statements. This clinical equipoise has resulted in significant variation in practice patterns. Currently, most CSC physicians base the timing of anticoagulation on clinical severity and infarct size, as seen on CT scan. Most physicians will defer anticoagulation anywhere from 5 to 14 days after ischemic stroke when infarct volume is extensive. In patients with small infarct volumes, assessed with CT or MRI, however, anticoagulation is often begun within 24-72 hours of stroke onset, and in some cases immediately after clinical assessment and CT scan.
Currently, Bayer has no data related to early use of rivaroxaban after TIA or ischemic stroke. Although a randomized study of delayed versus early anticoagulation with rivaroxaban will ideally answer this question, at the moment, there is no feasibility or safety data. There is also insufficient data in the present literature to indicate what the true event rates for both symptomatic hemorrhagic transformation and recurrent cerebral ischemia are. These data can be obtained by prospectively collecting clinical and imaging data from patients who are treated, as per standard clinical practice in most Canadian stroke centres, within this 14-day period of clinical uncertainty. The results of this registry will be used to assess the safety and feasibility of a larger randomized controlled trial of early versus delayed rivaroxaban use after stroke/TIA.
Study Design:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients will be ≥ 18 years of age.
- •All patients will have a diagnosis of minor ischemic stroke, defined as NIHSS score ≤ 8, or Transient Ischemic Attack (TIA), defined as acute focal neurological deficits, with complete resolution of symptoms within 24 h of onset. In cases where onset time cannot be established, it will be considered to be the time when the patient was last known to be well.
- •Atrial Fibrillation (AF, paroxysmal or persistent). AF must be confirmed with ECG/Holter monitor, or by history (clinical documentation of previous AF must be provided).
- •All included patients will be prescribed rivaroxaban following their stroke/TIA.
排除标准
- •Acute or chronic renal failure, defined as eGFR <30 ml/min (Cockcroft Gault formula).
- •Known hypersensitivity to rivaroxaban.
- •Prior treatment with rivaroxaban or any other novel oral anticoagulant (including all Factor Xa antagonists). Treatment with warfarin prior to the stroke/TIA is acceptable, but enrolment cannot begin until the INR is ≤2.
- •Any significant ongoing systemic bleeding risk, i.e. active GI/GU bleeding or recent major surgery.
- •Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
- •Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator.
- •Hereditary or acquired haemorrhagic diathesis.
- •Stroke mimics (such as seizures, migraine etc.)
- •Contraindications to MRI will also be excluded, including metallic implants.
结局指标
主要结局
Symptomatic Hemorrhagic Transformation Rate
时间窗: 30 days post-treatment
PH2 associated with clinical deterioration, defined as worsening of NIHSS score of 4 or more points within 30 days of initiating anticoagulant therapy
次要结局
- Any parenchymal haemorrhage (PH1 or PH2) on follow-up MRI scan at 7±2 days post-enrolment.(7 days post-treatment)
- Systemic hemorrhagic complication rate within 90 days of enrolment.(90 days following enrollment)
- Recurrent Transient Ischemic Attack/Ischemic Stroke within 90 days of enrolment.(90 days following enrollment)
研究者
Ken Butcher
Assistant Professor
University of Alberta