Analysis of the Coagulopathy Developed by COVID-19 Infected Patients

COVID-19 Clinical Trial

— COVID-TGT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04356950
• Other study ID #: PHRC-I/2020/JCG-01
• Status: Completed
• Start date: April 28, 2020
• Est. completion date: June 2, 2022

Study information

• Verified date: September 2022
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: June 2, 2022
• Est. primary completion date: February 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• COVID-19
• Disseminated Intravascular Coagulation
• Hemostatic Disorders
• Sepsis
• Thrombin

Intervention

Other:
• Thrombin generation test assay
lag time, initial velocity, time-to-peak, thrombin peak, total thrombin generation time, extrinsic thrombin potential (ETP). Crude quantitative values and relative values (%, by reference to the one obtained with an invariant reference plasma). Both without the addition of purified thrombomodulin (TM-) and with the addition of purified thrombomodulin (TM+). The ability of TM to inhibit thrombin generation will be calculated as follows: [ETP (%)(TM+) / ETP (%)(TM-)].
• Fibrin generation markers assays
D-dimers (coagulation plus fibrinolysis), soluble fibrin monomers (coagulation only)

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	CHU de Limoges	Limoges
France	CHU de Montpellier	Montpellier
France	CHU de Nimes	Nîmes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28-day survival rate	Death yes/no during hopstilization, 28 days after admittence	1 month
Primary	Absolute thrombin generation test latent period	Seconds; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Relative thrombin generation test latent period compared to reference plasma	%; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Absolute thrombin generation test initial velocity	nmol/s; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Relative thrombin generation test initial velocity compared to reference plasma	%; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Relative thrombin generation test peak thrombin compared to reference plasma	%; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Absolute thrombin generation test peak thrombin	nmol/L; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Absolute thrombin generation test peak thrombin time	Seconds; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Relative thrombin generation test peak thrombin time compared to reference plasma	%; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Absolute thrombin generation test total thrombin generation time	seconds; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Relative thrombin generation test total thrombin generation time compared to reference plasma	%; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Absolute thrombin generation test endogenous thrombin potential	Seconds; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Primary	Relative thrombin generation test endogenous thrombin potential compared to reference plasma	%; without (TM-) and with (TM+) purified thrombomodulin	Day 0
Secondary	3-month survival rate	Death yes/no	3 months
Secondary	Transfer to intensive care unit during hospitalization	Yes/no	3 months
Secondary	Thrombotic complication during hospitalization	Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis)	3 months
Secondary	Plasma concentrations of D-dimers	µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II)	Day 0
Secondary	Plasma concentrations of soluble fibrin monomers	mg / L, measured by automated immunoagglutination (STA®-Liatest® FM)	Day 0