A Phase 2-3, Multi-Center, Randomized Trial to Study the Potential Benefit of Factor Xa Inhibitor (Rivaroxaban) Versus Standard of Care Low Molecular Weight Heparin (Lovenox) in Hospitalized Patients With COVID-19 (XACT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Death or 30-day all cause mortality
研究概览
简要总结
This study is a multicenter, randomized trial to study the potential benefit of treatments with a direct FXa inhibitor (rivaroxaban) versus standard of care dose subcutaneous low molecular weight heparin (LMWH) (Lovenox) in hospitalized subjects with COVID-19.
详细描述
As clinicians learn how to better care for hospitalized COVID-19 patients, the clinical picture of a hypercoagulable state with abnormal blood clotting has emerged. Fulminant heart, lung, kidney, and liver failure are hallmarks of COVID-19 non-survivors and have been associated with abnormal blood coagulation parameters, such as elevated D-Dimer levels. The current standard of care using prophylactic levels of subcutaneous heparin has not significantly mitigated the risk of patients entering a hypercoagulable state, however the dysregulated thrombotic and inflammatory events that drive poor outcomes in many COVID-19 patients may be amenable to early treatment with a factor Xa (FXa) inhibitor. The purpose of this study is to study the potential benefit of treatments with a direct FXa inhibitor (rivaroxaban) versus standard of care dose subcutaneous LMWH (Lovenox) in hospitalized subjects with COVID-19.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open label
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age 18-100 admitted to hospital with laboratory-confirmed SARS-CoV-2 infection
- •Not be intubated or mechanically ventilated or imminently at risk for same or ICU admission within 24 hours of enrollment.
- •Not be admitted for central nervous system (CNS) diagnosis
- •Not have a current history of a condition requiring full therapeutic anticoagulation such as venous thromboembolism, atrial fibrillation.
排除标准
- •Medical Conditions
- •Life expectancy of less than 6 months
- •Active or recent gastrointestinal bleeding in the past 6 months
- •Intracranial bleeding in the past 6 months
- •Major trauma or head trauma in the past 2 months
- •Major surgery in the past 2 months or planned within 2 weeks after completion of the study
- •Recent spinal or epidural procedures in the past 2 weeks
- •Ischemic stroke in the past 2 weeks
- •History of intracranial neoplasm, arteriovenous malformation or aneurysm
- •History of acquired or spontaneous impairment of hemostasis such as but not limited to hemophilia, idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), von Willebrand disease
- •Allergy to heparin or rivaroxaban or any factor Xa inhibitors, including a history of heparin-induced thrombocytopenia
- •History of antiphospholipid syndrome
- •End-stage renal failure requiring dialysis
- •Valvular heart disease requiring chronic anticoagulation
- •History of atrial fibrillation, atrial flutter or venous thromboembolic event (VTE) currently requiring anticoagulation
- •History of solid organ transplant requiring immunosuppressant therapy
- •Cancer requiring ongoing anticoagulation
- •History of cirrhosis or liver failure, hepatorenal syndrome
- •History of baseline bronchiectasis
- •History of systemic lupus erythematosus or other autoimmune diseases requiring immunosuppressant therapy.
- •Vital signs
- •Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mm Hg or diastolic blood pressure (DBP) > 105mm Hg. Subjects who have a transient, higher blood pressure elevation (SBP 180-200 mm Hg) may enter the study if a repeat confirmation is back in range prior to enrollment.
- •PT INR > 2.
- •Platelet < 90 10^3/µL
- •Total bilirubin > 3.0 mg/dL
- •Hemoglobin < 9.0 g/dL
- •Urine with gross hematuria (not due to menses)
- •Estimated glomerular filtration rate (GFR) less than 30 mL/min calculated with the Cockcroft-Gault formula
- •Medications
- •Patients on dual anti-platelet therapy
- •Patients taking hypoxia-inducible factor prolyl hydroxylase inhibitors (such as roxadustat.)
- •Erythropoiesis-stimulating agents (such as epoetin alfa, darbepoetin alfa)
- •Other COVID-19 drug studies or trials
- •Any COVID19 vaccination trials
- •Experimental COVID drug trial except for treatment(s) that has become accepted standard of care.
研究组 & 干预措施
Adaptive Dosing: Enoxaparin
- Low 40mg subcutaneous (SQ) daily, or
- Intermediate 40mg SQ q12 hours, or
- Therapeutic 1mg/kg SQ q12 hours
干预措施: Enoxaparin (Drug)
Adaptive Dosing: Rivaroxaban
- Low 10mg po daily
- Intermediate 10mg po daily
- Therapeutic 20mg po daily
干预措施: Rivaroxaban (Drug)
结局指标
主要结局
Death or 30-day all cause mortality
时间窗: 30 days
Mechanical ventilation, intubation
时间窗: 30 days
Transfer to an ICU setting
时间窗: 30 days
次要结局
- Major bleeding event(30 days)
- Time to recovery (defined as no limitation or minor limitation in activity level or hospitalized but require no oxygen)(30 days)
- New requirement for hemodialysis (HD) or continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO)(30 days)
- New thrombotic events(30 days)