Enoxaparin at Prophylactic or Therapeutic Doses With Monitoring of Outcomes in Subjects Infected With COVID-19: a Pilot Study on 300 Cases Enrolled at ASST-FBF-Sacco
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 1
- 主要终点
- Progression of respiratory failure
研究概览
简要总结
SINGLE CENTER PHASE III INTERVENTIONAL RANDOMIZED CONTROLLED TRIAL comparing efficacy and safety of enoxaparin at prophylactic dose (standard treatment) and enoxaparin at therapeutic dose (OFF-LABEL treatment) in 300 COVID-19 infected patients with moderate-severe respiratory failure (PaO2/FiO2<250) and/or increased D-dimer levels enrolled in different Units (Infectious disease, Internal Medicine, Emergency Medicine, Pneumology) of Azienda Socio Sanitaria Territoriale Fatebenefratelli Sacco (ASST-FBF-SACCO).
详细描述
Patients with COVID-19 are at high risk of developing a venous thromboembolism (VTE) and it is essential that effective thromboprophylaxis with parenteral drugs (LMWH, UFH) is considered for all patients admitted to hospital especially in case of severe pneumonia.
The aim of the study is the evaluation of efficacy and safety of enoxaparin at prophylactic dose (standard treatment) as compared to enoxaparin at therapeutic dose (OFF-LABEL treatment) in 300 COVID-19 infected patients with moderate-severe respiratory failure (PaO2/FiO2<250) and/or increased D-dimer levels.
After the admission to different Units (Infectious disease, Internal Medicine, Emergency Medicine, Pneumology), enoxaparin at prophylactic dose (standard of care) will be prescribed to all patients.
The randomization of the single patient will be made when the the inclusion criteria (PaO2/FiO2 <250 and/or D-dimer >2000 ng/) will be satisfied. Patients with increased bleeding risk will be excluded (exclusion criteria).
Patients will be divided into two arms:
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •COVID-19 related pneumonia with moderate-severe respiratory failure (PaO2/FiO2<250) and/or markedly increased D-dimer level (>2000 ng/mL)
- •Signed informed consent
排除标准
- •age < 18 and > 80 yrs
- •history of bleeding (peptic ulcer, esophageal varices, cerebral aneurysm, cancer at high risk of bleeding, cirrhosis, hemorrhagic stroke < 1 year)
- •thrombocytopenia (<100 x109/L)
- •anemia (Hb < 8 g/dl)
- •coagulation abnormalities (PT e/o aPTT > 1.5; fibrinogen < 150 mg/dl)
- •consumption coagulopathy (ISTH criteria) [15, 16]
- •deep vein thrombosis or pulmonary embolism
- •dual antiplatelet therapy
- •ongoing anticoagulant therapy
- •allergic reaction to LMWH
- •previous heparin-induced thrombocytopenia
- •major surgery < 1 month; neurosurgery <3 months; eye surgery <3 months
- •pregnancy
- •arterial hypertension (SBPS>160 mm Hg; DBP>100 mm Hg)
- •renal failure (creatinine clearance 30 ml/min)
- •ICU admission or endotracheal intubation
研究组 & 干预措施
Enoxaparin at prophylactic dose
Enoxaparin at prophylactic dose: standard 4.000 IU QD via subcutaneous injection (6000 IU if body weight>100 kg)
干预措施: Enoxaparin (Drug)
Enoxaparin at therapeutic dose
Enoxaparin at therapeutic dose : 70 U/Kg b.i.d. (every 12 h)
In order to easily calculate the correct therapeutic dose of enoxaparin for each patient, a simplified categorization will be applied, as follows:
- weight < 65 Kg: 4.000 IU b.i.d. (every 12 h)
- weight ≥ 65 Kg: 6.000 IU b.i.d. (every 12 h)
- weight ≥ 100 Kg: 8.000 IU b.i.d. (every 12 h) The most appropriate dose will be evaluated in patients with creatinine clearance between 30 and 50 ml/min
干预措施: Enoxaparin (Drug)
结局指标
主要结局
Progression of respiratory failure
时间窗: 30 days from enrollment
Progression of respiratory failure defined as percentage of patients undergoing oro-tracheal intubation
Mortality rate
时间窗: 30 days from enrollment
Mortality registered during the time frame
Number of major bleeding episodes
时间窗: up to 6 months from randomization
Major bleeding (ISTH criteria) and/or clinically relevant non-major bleeding
次要结局
- Respiratory function improvement(1 week from randomization)
- Number of major cardiovascular events(6 months from randomization)
- Deep Vein Thrombosis(6 months from randomization)
研究者
Maddalena Alessandra Wu
Principal Investigator
ASST Fatebenefratelli Sacco