Analysis of the Coagulopathy Developed by COVID-19 Infected Patients: Thrombin Generation Potential in COVID-19 Infected Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 175
- 试验地点
- 4
- 主要终点
- Absolute thrombin generation test latent period
研究概览
简要总结
Increased D-dimers at admission of COVID-19 infected patients entering hospital due to a severe disease is a risk factor for death. Understanding this acquired coagulopathy is a prerequisite before specific interventional studies. The study investigators aim to apply a normalized and automated thrombin generation test (TGT), developed for testing the thrombotic risk (triggered by 5 pM Tissue Factor, with a purified thrombomodulin (TM) challenge) and to study its association with survival.
详细描述
Accumulating data describe, in COVID-19 severely infected patients necessitating hospitalized medical support, the development of an acquired coagulopathy, from a sepsis-induced coagulopathy to an overt-DIC, which is a strong risk factor for death. Understanding this coagulopathy is a prerequisite before specific interventional studies. Conventional coagulation tests, like prothrombin time PT and aPTT, only reflect 5% of the total thrombin generation and are insensitive to the patients' natural anticoagulants. The investigators thus wish to analyze the coagulopathy of SARS-CoV-2 using a global analytical test reflecting the full complexity of thrombin generation then inhibition, the thrombin generation test (TGT), in its version designed to analyze the thrombotic risk (initiation by an intermediate concentration of human Tissue: 5 pM), in its fully automated and standardized technical version. This test analyzes not only the generation of thrombin and its various informative phases (initiation phase, propagation phase culminating at the peak of formation, inhibition phase with natural anticoagulants) but also the capacity for an exogenous addition of purified thrombomodulin (TM), which quantifies the anticoagulant activity of the patient's protein C activated by thrombin, to inhibit this generation of thrombin.
The aim is to assay this TGT version in a centralized way, on the patients' plasma obtained at hospital admission, just after checking the positive COVID-19 testing , together with the traditional blood tests including platelet counts, PT, D-dimers (DDi) and soluble fibrin monomers (FMs). The various quantitative biological parameters describing the results of the TGT assay, together with relevant covariates, will be tested using multivariate analysis for their capacity to be risk factors for clinically-relevant qualitative outcomes.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 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
- •Patient with SARS-CoV-2 infection entering hospitalization with or without resuscitation
- •The patient (or their carer) must have given their free and informed consent and signed the consent form
- •The patient must be a member or beneficiary of a health insurance plan
排除标准
- •Pregnant or breastfeeding patient
- •It is impossible to give the subject informed information
- •The patient is under safeguard of justice or state guardianship
- •Thrombotic events during treatment: flare-up of venous thromboembolism, flare-up of atherothrombosis.
- •Long-term anticoagulant treatment (anti-vitamin K, direct oral anticoagulant).
- •Chronic anti-aggregation treatment.
- •Pre-existing constitutive or acquired known coagulation pathology: hemorrhagic diseases (thrombocytopenia, thrombocytopathy, hemophilia, von Willebrand's disease, hemorrhagiparous factor deficiency), and for thrombophilia (deficits in antithrombin, protein C or S , Factor V Leiden or Prothrombin 20201A mutation).
结局指标
主要结局
Absolute thrombin generation test latent period
时间窗: Day 0
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test peak thrombin
时间窗: Day 0
nmol/L; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test peak thrombin time
时间窗: Day 0
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test total thrombin generation time compared to reference plasma
时间窗: Day 0
%; without (TM-) and with (TM+) purified thrombomodulin
28-day survival rate
时间窗: 1 month
Death yes/no during hopstilization, 28 days after admittence
Absolute thrombin generation test initial velocity
时间窗: Day 0
nmol/s; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test latent period compared to reference plasma
时间窗: Day 0
%; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test peak thrombin time compared to reference plasma
时间窗: Day 0
%; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test initial velocity compared to reference plasma
时间窗: Day 0
%; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test peak thrombin compared to reference plasma
时间窗: Day 0
%; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test total thrombin generation time
时间窗: Day 0
seconds; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test endogenous thrombin potential compared to reference plasma
时间窗: Day 0
%; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test endogenous thrombin potential
时间窗: Day 0
Seconds; without (TM-) and with (TM+) purified thrombomodulin
次要结局
- 3-month survival rate(3 months)
- Transfer to intensive care unit during hospitalization(3 months)
- Thrombotic complication during hospitalization(3 months)
- Plasma concentrations of D-dimers(Day 0)
- Plasma concentrations of soluble fibrin monomers(Day 0)