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NCT Number: NCT04356950

Analysis of the Coagulopathy Developed by COVID-19 Infected Patients

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.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Thrombin generation test assay

Other

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

Other

D-dimers (coagulation plus fibrinolysis), soluble fibrin monomers (coagulation only)

Primary outcomes

  1. 28-day survival rate

    Time frame: 1 month

    Death yes/no during hopstilization, 28 days after admittence

  2. Absolute thrombin generation test latent period

    Time frame: Day 0

    Seconds; without (TM-) and with (TM+) purified thrombomodulin

  3. Relative thrombin generation test latent period compared to reference plasma

    Time frame: Day 0

    %; without (TM-) and with (TM+) purified thrombomodulin

  4. Absolute thrombin generation test initial velocity

    Time frame: Day 0

    nmol/s; without (TM-) and with (TM+) purified thrombomodulin

  5. Relative thrombin generation test initial velocity compared to reference plasma

    Time frame: Day 0

    %; without (TM-) and with (TM+) purified thrombomodulin

  6. Relative thrombin generation test peak thrombin compared to reference plasma

    Time frame: Day 0

    %; without (TM-) and with (TM+) purified thrombomodulin

  7. Absolute thrombin generation test peak thrombin

    Time frame: Day 0

    nmol/L; without (TM-) and with (TM+) purified thrombomodulin

  8. Absolute thrombin generation test peak thrombin time

    Time frame: Day 0

    Seconds; without (TM-) and with (TM+) purified thrombomodulin

  9. Relative thrombin generation test peak thrombin time compared to reference plasma

    Time frame: Day 0

    %; without (TM-) and with (TM+) purified thrombomodulin

  10. Absolute thrombin generation test total thrombin generation time

    Time frame: Day 0

    seconds; without (TM-) and with (TM+) purified thrombomodulin

  11. Relative thrombin generation test total thrombin generation time compared to reference plasma

    Time frame: Day 0

    %; without (TM-) and with (TM+) purified thrombomodulin

  12. Absolute thrombin generation test endogenous thrombin potential

    Time frame: Day 0

    Seconds; without (TM-) and with (TM+) purified thrombomodulin

  13. Relative thrombin generation test endogenous thrombin potential compared to reference plasma

    Time frame: Day 0

    %; without (TM-) and with (TM+) purified thrombomodulin

Secondary outcomes

  1. 3-month survival rate

    Time frame: 3 months

    Death yes/no

  2. Transfer to intensive care unit during hospitalization

    Time frame: 3 months

    Yes/no

  3. Thrombotic complication during hospitalization

    Time frame: 3 months

    Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis)

  4. Plasma concentrations of D-dimers

    Time frame: Day 0

    µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II)

  5. Plasma concentrations of soluble fibrin monomers

    Time frame: Day 0

    mg / L, measured by automated immunoagglutination (STA®-Liatest® FM)

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Registry information

Official study title

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

Acronym: COVID-TGT

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Apr 22, 2020
Registry last updated
Dec 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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