COVID-TGT: Analysis of the Coagulopathy Developed by COVID-19 Infected Patients

Sponsor

Centre Hospitalier Universitaire de Nīmes (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04356950

Collaborator

(none)

175

Enrollment

Locations

26.1

Anticipated Duration (Months)

43.8

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sepsis Blood Coagulation Disorders Thrombin Disseminated Intravascular Coagulation COVID-19	Other: Thrombin generation test assay Other: Fibrin generation markers assays

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.

Study Design

Study Type:

Observational

Actual Enrollment :

175 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Analysis of the Coagulopathy Developed by COVID-19 Infected Patients: Thrombin Generation Potential in COVID-19 Infected Patients

Actual Study Start Date :

Apr 28, 2020

Actual Primary Completion Date :

Feb 14, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Outcome Measures

Primary Outcome Measures

28-day survival rate [1 month]
Death yes/no during hopstilization, 28 days after admittence
Absolute thrombin generation test latent period [Day 0]
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test latent period compared to reference plasma [Day 0]
%; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test initial velocity [Day 0]
nmol/s; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test initial velocity compared to reference plasma [Day 0]
%; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test peak thrombin compared to reference plasma [Day 0]
%; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test peak thrombin [Day 0]
nmol/L; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test peak thrombin time [Day 0]
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test peak thrombin time compared to reference plasma [Day 0]
%; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test total thrombin generation time [Day 0]
seconds; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test total thrombin generation time compared to reference plasma [Day 0]
%; without (TM-) and with (TM+) purified thrombomodulin
Absolute thrombin generation test endogenous thrombin potential [Day 0]
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Relative thrombin generation test endogenous thrombin potential compared to reference plasma [Day 0]
%; without (TM-) and with (TM+) purified thrombomodulin

Secondary Outcome Measures

3-month survival rate [3 months]
Death yes/no
Transfer to intensive care unit during hospitalization [3 months]
Yes/no
Thrombotic complication during hospitalization [3 months]
Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis)
Plasma concentrations of D-dimers [Day 0]
µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II)
Plasma concentrations of soluble fibrin monomers [Day 0]
mg / L, measured by automated immunoagglutination (STA®-Liatest® FM)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).