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

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ClinicalTrials.gov Identifier: NCT04356950
Recruitment Status : Recruiting
First Posted : April 22, 2020
Last Update Posted : December 2, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes

Tracking Information
First Submitted Date April 16, 2020
First Posted Date April 22, 2020
Last Update Posted Date December 2, 2020
Actual Study Start Date April 28, 2020
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 27, 2020)
  • 28-day survival rate [ Time Frame: 1 month ]
    Death yes/no during hopstilization, 28 days after admittence
  • Absolute thrombin generation test latent period [ Time Frame: Day 0 ]
    Seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test latent period compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test initial velocity [ Time Frame: Day 0 ]
    nmol/s; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test initial velocity compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test peak thrombin compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test peak thrombin [ Time Frame: Day 0 ]
    nmol/L; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test peak thrombin time [ Time Frame: Day 0 ]
    Seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test peak thrombin time compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test total thrombin generation time [ Time Frame: Day 0 ]
    seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test total thrombin generation time compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test endogenous thrombin potential [ Time Frame: Day 0 ]
    Seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test endogenous thrombin potential compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
Original Primary Outcome Measures
 (submitted: April 20, 2020)
  • Survival rate during hospitalization [ Time Frame: 3 months ]
    % patients surviving hospitalization
  • Absolute thrombin generation test latent period [ Time Frame: Day 0 ]
    Seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test latent period compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test initial velocity [ Time Frame: Day 0 ]
    nmol/s; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test initial velocity compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test peak thrombin compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test peak thrombin [ Time Frame: Day 0 ]
    nmol/L; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test peak thrombin time [ Time Frame: Day 0 ]
    Seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test peak thrombin time compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test total thrombin generation time [ Time Frame: Day 0 ]
    seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test total thrombin generation time compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
  • Absolute thrombin generation test endogenous thrombin potential [ Time Frame: Day 0 ]
    Seconds; without (TM-) and with (TM+) purified thrombomodulin
  • Relative thrombin generation test endogenous thrombin potential compared to reference plasma [ Time Frame: Day 0 ]
    %; without (TM-) and with (TM+) purified thrombomodulin
Change History
Current Secondary Outcome Measures
 (submitted: April 27, 2020)
  • 3-month survival rate [ Time Frame: 3 months ]
    Death yes/no
  • Transfer to intensive care unit during hospitalization [ Time Frame: 3 months ]
    Yes/no
  • Thrombotic complication during hospitalization [ Time Frame: 3 months ]
    Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis)
  • Plasma concentrations of D-dimers [ Time Frame: Day 0 ]
    µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II)
  • Plasma concentrations of soluble fibrin monomers [ Time Frame: Day 0 ]
    mg / L, measured by automated immunoagglutination (STA®-Liatest® FM)
Original Secondary Outcome Measures
 (submitted: April 20, 2020)
  • Transfer to intensive care unit during hospitalization [ Time Frame: 3 months ]
    Yes/no
  • Thrombotic complication during hospitalization [ Time Frame: 3 months ]
    Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis)
  • Plasma concentrations of D-dimers [ Time Frame: Day 0 ]
    µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II)
  • Plasma concentrations of soluble fibrin monomers [ Time Frame: Day 0 ]
    mg / L, measured by automated immunoagglutination (STA®-Liatest® FM)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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
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.

Study Type Observational
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Consecutive patients hospitalized for SARS-CoV-2 infection with symptomatology / severity requiring hospital treatment.
Condition
  • Sepsis
  • Blood Coagulation Disorders
  • Thrombin
  • Disseminated Intravascular Coagulation
  • COVID-19
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-)].
  • Other: Fibrin generation markers assays
    D-dimers (coagulation plus fibrinolysis), soluble fibrin monomers (coagulation only)
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 20, 2020)
175
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
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).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Jean-Christophe Gris 04 66 68 32 11 jean.christophe.gris@chu-nimes.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT04356950
Other Study ID Numbers PHRC-I/2020/JCG-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Centre Hospitalier Universitaire de Nīmes
Study Sponsor Centre Hospitalier Universitaire de Nīmes
Collaborators Not Provided
Investigators
Principal Investigator: Jean-Christophe Gris CHU Nimes
PRS Account Centre Hospitalier Universitaire de Nīmes
Verification Date December 2020