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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-A01068-31 | Other Identifier | ANSM |
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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 28-day survival rate | Death yes/no during hopstilization, 28 days after admittence | 1 month |
| Absolute thrombin generation test latent period | Seconds; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Relative thrombin generation test latent period compared to reference plasma | %; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Absolute thrombin generation test initial velocity | nmol/s; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Relative thrombin generation test initial velocity compared to reference plasma | %; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Relative thrombin generation test peak thrombin compared to reference plasma | %; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Absolute thrombin generation test peak thrombin | nmol/L; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Absolute thrombin generation test peak thrombin time | Seconds; without (TM-) and with (TM+) purified thrombomodulin |
| Measure | Description | Time Frame |
|---|---|---|
| 3-month survival rate | Death yes/no | 3 months |
| Transfer to intensive care unit during hospitalization | Yes/no | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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Consecutive patients hospitalized for SARS-CoV-2 infection with symptomatology / severity requiring hospital treatment.
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Christophe Gris | CHU Nimes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Bordeaux | Bordeaux | France | ||||
| CHU de Limoges |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36608393 | Result | 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. |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D001778 | Blood Coagulation Disorders |
| D004211 | Disseminated Intravascular Coagulation |
| D000086382 | COVID-19 |
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| Day 0 |
| Relative thrombin generation test peak thrombin time compared to reference plasma | %; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Absolute thrombin generation test total thrombin generation time | seconds; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Relative thrombin generation test total thrombin generation time compared to reference plasma | %; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Absolute thrombin generation test endogenous thrombin potential | Seconds; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Relative thrombin generation test endogenous thrombin potential compared to reference plasma | %; without (TM-) and with (TM+) purified thrombomodulin | Day 0 |
| Thrombotic complication during hospitalization | Yes/no (deep vein thrombosis, pulmonary embolism, atherothrombosis flare, arterial thrombosis) | 3 months |
| Plasma concentrations of D-dimers | µg / L, assayed by automated enzyme linked fluorescent assay (Vidas® D-dimers Exclusion ™ II) | Day 0 |
| Plasma concentrations of soluble fibrin monomers | mg / L, measured by automated immunoagglutination (STA®-Liatest® FM) | Day 0 |
| Limoges |
| France |
| CHU de Montpellier | Montpellier | France |
| CHU de Nimes | Nîmes | France |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D019851 | Thrombophilia |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |