Clinical trial NCT04356950: Analysis of the Coagulopathy Developed by COVID-19 Infected Patients
Official title: Analysis of the Coagulopathy Developed by COVID-19 Infected Patients: Thrombin Generation Potential in COVID-19 Infected Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Blood Coagulation Disorders
Thrombin
Disseminated Intravascular Coagulation
COVID-19
Keywords: coagulation
survival
thrombin generation test
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2020-04-22
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients hospitalized for SARS-CoV-2 infection with symptomatology / severity requiring hospital treatment.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: 28-day survival rate
timeFrame: 1 month
measure: Absolute thrombin generation test latent period
timeFrame: Day 0
measure: Relative thrombin generation test latent period compared to reference plasma
timeFrame: Day 0
measure: Absolute thrombin generation test initial velocity
timeFrame: Day 0
measure: Relative thrombin generation test initial velocity compared to reference plasma
timeFrame: Day 0
measure: Relative thrombin generation test peak thrombin compared to reference plasma
timeFrame: Day 0
measure: Absolute thrombin generation test peak thrombin
timeFrame: Day 0
measure: Absolute thrombin generation test peak thrombin time
timeFrame: Day 0
measure: Relative thrombin generation test peak thrombin time compared to reference plasma
timeFrame: Day 0
measure: Absolute thrombin generation test total thrombin generation time
timeFrame: Day 0
measure: Relative thrombin generation test total thrombin generation time compared to reference plasma
timeFrame: Day 0
measure: Absolute thrombin generation test endogenous thrombin potential
timeFrame: Day 0
measure: Relative thrombin generation test endogenous thrombin potential compared to reference plasma
timeFrame: Day 0
Secondary outcomes:
measure: 3-month survival rate
timeFrame: 3 months
measure: Transfer to intensive care unit during hospitalization
timeFrame: 3 months
measure: Thrombotic complication during hospitalization
timeFrame: 3 months
measure: Plasma concentrations of D-dimers
timeFrame: Day 0
measure: Plasma concentrations of soluble fibrin monomers
timeFrame: Day 0
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Limoges
country: France
facility: CHU de Limoges
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nîmes
country: France
facility: CHU de Nimes
Study officials:
affiliation: CHU Nimes
name: Jean-Christophe Gris
role: PRINCIPAL_INVESTIGATOR
References: