Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04356950
Recruitment Status : Recruiting
First Posted : April 22, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes

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
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.

Layout table for study information
Study Type : Observational
Estimated 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 : April 28, 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine



Intervention Details:
  • 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)


Primary Outcome Measures :
  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 Outcome Measures :
  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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive patients hospitalized for SARS-CoV-2 infection with symptomatology / severity requiring hospital treatment.
Criteria

Inclusion Criteria:

  • Patient with SARS-CoV-2 infection (confirmed by positive PCR test) 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04356950


Contacts
Layout table for location contacts
Contact: Jean-Christophe Gris 04 66 68 32 11 jean.christophe.gris@chu-nimes.fr

Locations
Layout table for location information
France
CHU de Bordeaux Not yet recruiting
Bordeaux, France
Contact: Charles Cazenave    05.56.79.56.79    charles.cazenave@chu-bordeaux.fr   
Principal Investigator: Charles Cazenave         
CHU de Limoges Not yet recruiting
Limoges, France
Contact: Jean-François Faucher    05.55.05.66.44    jean-francois.faucher@unilim.fr   
Principal Investigator: Jean-François Faucher         
CHU de Montpellier Not yet recruiting
Montpellier, France
Contact: Isabelle Quere    04.67.33.70.28    i-quere@chu-montpellier.fr   
Principal Investigator: Isabelle Quere         
Sub-Investigator: Vincent Le Moing         
Sub-Investigator: Kada Klouche         
CHU de Nimes Recruiting
Nîmes, France
Contact: Anissa Megzari    04.66.68.42.36    drc@chu-nimes.fr   
Principal Investigator: Jean-Christophe Gris         
Sub-Investigator: Albert Sotto         
Sub-Investigator: Didier Laureillard         
Sub-Investigator: Catherine Lechiche         
Sub-Investigator: Claudine Barbuat         
Sub-Investigator: Jean-Marc Mauboussin         
Sub-Investigator: Paul Loubet         
Sub-Investigator: Jean-Yves Lefrant         
Sub-Investigator: Laurent Muller         
Sub-Investigator: Saber D Barbar         
Sub-Investigator: Claire Roger         
Sub-Investigator: Antonia Perez Martin         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Investigators
Layout table for investigator information
Principal Investigator: Jean-Christophe Gris CHU Nimes
Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT04356950    
Other Study ID Numbers: PHRC-I/2020/JCG-01
First Posted: April 22, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Nīmes:
coagulation
survival
thrombin generation test
Additional relevant MeSH terms:
Layout table for MeSH terms
Hemostatic Disorders
Blood Coagulation Disorders
Disseminated Intravascular Coagulation
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Thrombophilia
Thrombin
Hemostatics
Coagulants