Randomized, Pragmatic, Open Controlled Multicentre Study, Evaluating the Use of Rivaroxaban in Mild or Moderate COVID-19 Patients
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 660
- 试验地点
- 36
- 主要终点
- Venous thromboembolic events (VTE)
研究概览
简要总结
There are several ways in which the COVID-19 pandemic may affect the prevention and management of thrombotic and thromboembolic disease, either direct effect or the indirect effects of infection, such as through severe illness and hypoxia, may predispose patients to thrombotic events. The severe inflammatory response, critical illness, and underlying traditional risk factors may all predispose to thrombotic events. Therefore, considering the high-risk profile of cardiovascular comorbidities in patients with COVID-19, it is scientifically relevant to evaluate the use of anticoagulants as an adjunctive treatment in the context of COVID-19. Indeed, it will be tested the hypothesis that the use of moderate dose of rivaroxaban has a beneficial effect in the treatment of patients with a confirmed or probable diagnosis of COVID-19 infection, with no clear indication for hospitalization (mild and moderate cases) upon initial medical care, by reducing the need of hospitalization due to complications related to COVID-19.
详细描述
Initial studies suggest an inflammatory state and hypercoagulation in individuals with COVID-19. Apparently, the fact that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to Angiotensin Converting Enzyme 2 (ACE2) receptors can lead to ACE2 depletion by SARS-CoV-2 favoring the "harmful" ACE1 / angiotensin II and promoting tissue damage, including stroke. Recent observational studies indicate a higher rate of thromboembolism in patients with COVID-19, especially those in severe condition. They also report that, in patients treated with anticoagulants, complication rates were lower as compared with those not receiving anticoagulant therapies.
More recently, in a post-mortem study of patients with Covid-19 compared to recently published cases of influenza, the histopathological pattern on the periphery of the lungs of patients with Covid-19 revealed a diffuse alveolar lesion with infiltration of perivascular T cells and other vascular aspects, consisting of severe endothelial damage (endothelitis) associated with the presence of intracellular viruses and broken cell membranes. In addition, pulmonary vessels showed generalized thrombosis with microangiopathy, and alveolar capillary microthrombi were much more frequent in patients with COVID-19 than with severe influenza respiratory conditions.
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
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
- •Adults ≥ 18 years old;
- •Evaluated in the emergency unit with probable or confirmed infection by COVID-19;
- •Time between symptoms and inclusion ≤ 07 days *;
- •Present mild or moderate signs and symptoms, with no clear indication for hospitalization;
- •Present at least 2 risk factors for complication:
- •Hypertension
- •Diabetes mellitus
- •Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases
- •Immunosuppression
- •Obesity (BMI> 30)
- •History of non-active cancer
- •Bed restriction or reduced mobility (≥50% of the wake time without walking)
- •Previous history of VTE
- •Use of oral hormonal contraceptives
排除标准
- •Patients <18 years old;
- •Hospitalization indication upon first medical care;
- •Positive test for influenza in the first visit;
- •Any known liver disease associated with coagulopathy; INR (International Normalized Ratio) > 1.5;
- •Pregnant, lactating or with the possibility of becoming pregnant and without using an adequate contraceptive method;
- •High risk of bleeding; History of bronchiectasis or pulmonary cavitation, Significant bleeding in the last 3 months, Active gastroduodenal ulcer, history of recent bleeding (within 3 months) or a high risk of bleeding;
- •Stroke within 1 month or any history of hemorrhagic or lacunar stroke or any intracranial bleeding or any intracranial neoplasia, brain metastasis, arteriovenous malformation or brain aneurysm;
- •Severe heart failure with left ventricular ejection fraction <30% (echocardiogram or other validated method previously documented) or symptoms of heart failure class III or IV of the New York Heart Association (NYHA);
- •Estimated glomerular filtration rate (eGFR) <30 mL / min;
- •Clinical indication for dual antiplatelet therapy or anticoagulation therapy (VTE, atrial fibrillation / flutter, mechanical valve prosthesis);
- •Marked thrombocytopenia (platelets <50,000 / mm3);
- •Non-cardiovascular disease that is associated with a poor prognosis, for example, active cancer (excluding non-melanoma skin cancer) defined as cancer without remission or requiring active chemotherapy or adjuvant therapies such as immunotherapy or radiation therapy or that increases the risk of an adverse reaction to the evaluated interventions;
- •History of hypersensitivity or known contraindication to rivaroxaban;
- •Systemic treatment with strong inhibitors of Cytochrome P450 3A4 (CYP3A4) and glycoprotein p (Pgp) (for example, systemic azole antimycotics, such as ketoconazole and human immunodeficiency virus [HIV] protein inhibitors, such as ritonavir) or strong inducers of CYP 3A4, that is, rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine;
- •Current treatment being tested;
- •Concomitant participation in another study with experimental drugs in the context of COVID;
- •Use of chloroquine or hydroxychloroquine associated with azithromycin;
- •Active cancer;
- •Other contraindications to rivaroxaban;
研究组 & 干预措施
Rivaroxaban 10 mg
Participants will receive, from the 1st to the 14th day, a dose of 10 mg of rivaroxaban - OA (Oral Administration).
干预措施: Rivaroxaban 10 mg (Drug)
结局指标
主要结局
Venous thromboembolic events (VTE)
时间窗: Within 30 days from randomization
Defined as deep venous thrombosis, acute pulmonary embolism, other major venous thrombotic events.
Mechanical ventilation free-survival
时间窗: Within 30 days from randomization
Defined as survival without requirement of mechanical ventilation.
Major Adverse Cardiovascular Events (MACE)
时间窗: Within 30 days from randomization
Defined as acute myocardial infarction, stroke or acute limb ischemia
Out-of-hospital death not attributed to major injury
时间窗: Within 30 days from randomization
Death that occurred out of hospital due to any cause not related to trauma or other major injury
次要结局
- Time from randomization to hospitalization(30 days from randomization)
- Length of Hospitalization(30 days from randomization)
- Hospitalization in Intensive Care Unit(30 days from randomization)
- Clinical requirement of mechanical ventilation(30 days from randomization)
- Clinical duration of mechanical ventilation(30 days from randomization)
- Composite vascular endpoint I(30 days from randomization)
- Composite vascular endpoint II(30 days from randomization)
- Major Bleeding(30 days from randomization)
- Mortality(30 days from randomization)
研究者
Álvaro Avezum Junior
Research Manager - International Research Center
Hospital Alemão Oswaldo Cruz