Analysis of the Coagulopathy Developed by COVID-19 Infected Patients

NCT04356950 | Completed

• 2 other identifiers: PHRC-I/2020/JCG-012020-A01068-31
• Study Type: observational
• Target: 175
• Locations: 1 country
• Sites: 4

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.

Conditions

Sepsis; Thrombin; Disseminated Intravascular Coagulation; COVID-19; Blood Coagulation Disorders

Keywords

coagulation; survival; thrombin generation test

Outcome Measures

Primary Outcomes (13)

• 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

  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

Secondary Outcomes (5)

• 3-month survival rate

  3 months

• Transfer to intensive care unit during hospitalization

  3 months

• Thrombotic complication during hospitalization

  3 months

• Plasma concentrations of D-dimers

  Day 0

• Plasma concentrations of soluble fibrin monomers

  Day 0

Interventions

Fibrin generation markers assays OTHER

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

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: \[ETP (%)(TM+) / ETP (%)(TM-)\].

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients hospitalized for SARS-CoV-2 infection with symptomatology / severity requiring hospital treatment.

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (4)

CHU de Bordeaux

Bordeaux, France

Location

CHU de Limoges

Limoges, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU de Nimes

Nîmes, France

Location

Related Publications (1)

• 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.

  PMID: 36608393 RESULT

MeSH Terms

Conditions

Sepsis; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; COVID-19; Thrombosis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Thrombophilia; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jean-Christophe Gris

  CHU Nimes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 22, 2020
• Study Start: April 28, 2020
• Primary Completion: February 14, 2022
• Study Completion: February 14, 2022
• Last Updated: December 4, 2025

Record last verified: 2022-09

Locations

FR (4)