Randomised Controlled Trial Comparing High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy Not Requiring Invasive Mechanical Ventilation
试验速览
- 阶段
- 3 期
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:
研究概览
简要总结
Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation.
Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are:
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More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay:
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Death
-
Acute Myocardial Infarction [AMI]
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Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]
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Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation
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Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation
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Similar in terms of major bleeding risk during hospital stay
详细描述
This is a multicentre, randomised controlled, open label, investigator sponsored, two arms study.
The study will involve 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Diseases Units, 1 Respiratory Diseases Unit.
Patients who satisfy all inclusion criteria and do not have any exclusion criteria and have signed written informed consent, will be randomly assigned to a Low-Dose LMWH group (Control Group) or High-Dose LMWH group (Intervention Group) in a 1:1 ratio.
Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 IU subcutaneously once day).
Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table.
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
- Single (Investigator)
盲法说明
Randomisation will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (<75/≥75 years); 3) BMI (<30/≥30); 4) Co-morbidities (0-1/>2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment.
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
- 未提供
排除标准
- •Invasive mechanical ventilation
- •Thrombocytopenia (platelet count < 80.000 mm3)
- •Coagulopathy: INR >1.5, aPTT ratio > 1.4
- •Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min)
- •Known hypersensitivity to enoxaparin
- •History of heparin induced thrombocytopenia
- •Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations)
- •Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves).
- •Concomitant double antiplatelet therapy
- •Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed
- •Pregnancy or breastfeeding or positive pregnancy test
- •Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition)
- •Lack or withdrawal of informed consent
研究组 & 干预措施
Low-Dose LMWH
Enoxaparin 4000 IU daily
干预措施: Enoxaparin (Drug)
High-Dose LMWH
Enoxaparin 70 IU/kg twice daily
干预措施: Enoxaparin (Drug)
结局指标
主要结局
Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:
时间窗: through study completion, up to 30 days
1. Death 2. Acute Myocardial Infarction \[AMI\] 3. Objectively confirmed, symptomatic arterial or venous thromboembolism \[TE\] 4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation 5. Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation
次要结局
- Any of the following events occurring within the hospital stay(through study completion, up to 30 days)
- Mortality at 30 days(30 days)
研究者
Marco Marietta
Head, Hemostasis and Thrombosis Unit
Azienda Ospedaliero-Universitaria di Modena