SepsisCOVID-TGTNCT04356950
Analysis of the Coagulopathy Developed by COVID-19 Infected Patients
An observational study of Sepsis and Blood Coagulation Disorders, run by Centre Hospitalier Universitaire de Nīmes at 4 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Blood Coagulation Disorders, Thrombin
- What is being tested?
- Thrombin generation test assay and Fibrin generation markers assays
- How many people
- 175 participants
- Where
- 4 sitesFrance
- Study dates
- 28 Apr 2020to 14 Feb 2022
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive patients hospitalized for SARS-CoV-2 infection with symptomatology / severity requiring hospital treatment.
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
4 sites in 1 country.
France4 sites
CHU de Bordeaux
Bordeaux
CHU de Limoges
Limoges
CHU de Montpellier
Montpellier
CHU de Nimes
Nîmes
About this study
Official title: Analysis of the Coagulopathy Developed by COVID-19 Infected Patients: Thrombin Generation Potential in 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.
Read the 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.
- Conditions
- Sepsis, Blood Coagulation Disorders, Thrombin, Disseminated Intravascular Coagulation, COVID-19
- Being tested
- Thrombin generation test assay, Fibrin generation markers assays
- Keywords
- coagulation, survival, thrombin generation test
- Medical subject headings
- Sepsis, Blood Coagulation Disorders, Disseminated Intravascular Coagulation, COVID-19, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thrombin generation test assayOther
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 assaysOther
D-dimers (coagulation plus fibrinolysis), soluble fibrin monomers (coagulation only)
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day survival rate
Death yes/no during hopstilization, 28 days after admittence
Measured: 1 month
Absolute thrombin generation test latent period
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Relative thrombin generation test latent period compared to reference plasma
%; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Absolute thrombin generation test initial velocity
nmol/s; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Relative thrombin generation test initial velocity compared to reference plasma
%; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Relative thrombin generation test peak thrombin compared to reference plasma
%; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Absolute thrombin generation test peak thrombin
nmol/L; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Absolute thrombin generation test peak thrombin time
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Relative thrombin generation test peak thrombin time compared to reference plasma
%; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Absolute thrombin generation test total thrombin generation time
seconds; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Relative thrombin generation test total thrombin generation time compared to reference plasma
%; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Absolute thrombin generation test endogenous thrombin potential
Seconds; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Relative thrombin generation test endogenous thrombin potential compared to reference plasma
%; without (TM-) and with (TM+) purified thrombomodulin
Measured: Day 0
Secondary outcomes (5)
3-month survival rate
Death yes/no
Measured: 3 months
Transfer to intensive care unit during hospitalization
Yes/no
Measured: 3 months
Thrombotic complication during hospitalization
Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis)
Measured: 3 months
Plasma concentrations of D-dimers
µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II)
Measured: Day 0
Plasma concentrations of soluble fibrin monomers
mg / L, measured by automated immunoagglutination (STA®-Liatest® FM)
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start28 Apr 2020
- Primary completion14 Feb 2022
- Study completion14 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nīmes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Christophe Gris, Principal investigator, CHU Nimes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04356950
- Sponsor's protocol ID
- PHRC-I/2020/JCG-01
- Other IDs
- 2020-A01068-31
- Acronym
- COVID-TGT
- Status last verified
- Sep 2022
- First submitted
- 16 Apr 2020
- Last updated
- 4 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gris JC, Guillotin F, Dos Santos TP, Chea M, Loubet P, Laureillard D, Sotto A, Muller L, Barbar SD, Roger C, Lefrant JY, Jung B, Klouche K, Mura T, Quere I, Perez-Martin A. Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study. Thromb Res. 2023 Feb;222:85-95. doi: 10.1016/j.thromres.2022.12.019. Epub 2023 Jan 2.
PubMed 36608393