Thrombomodulin-modified Thrombin Generation Assay (TGA-TM) in Patients With Critical Infections

Sponsor

Medical University of Vienna (Other)

Overall Status

Completed

CT.gov ID

NCT04356144

Collaborator

Medical Scientific Fund of the Mayor of Vienna (Other)

Enrollment

Location

9.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Inflammation and abnormalities in laboratory coagulation tests are inseparably tied. For example, coagulation abnormalities are nearly universal in septic patients. Coagulation disorders have also been reported in many patients with severe courses of Coronavirus disease 2019 (Covid-19). But it is difficult to assess these changes. Global coagulation tests have been shown to incorrectly assess in vivo coagulation in patients admitted to intensive care units. But other tests are available. Thrombin generation assay (TGA) is a laboratory test which allows the assessment of an individual's potential to generate thrombin. But also in conventional TGA the protein C system is hardly activated because of the absence of endothelial cells (containing natural thrombomodulin) in the plasma sample. Therefore the investigators add recombinant human thrombomodulin to a conventional TGA. Thereby the investigators hope to be able to depict in vivo coagulation more closely than global coagulation tests do.

Condition or Disease	Intervention/Treatment	Phase
Disseminated Intravascular Coagulation Critical Illness Sars-CoV2 Viral Infection Coagulation Disorder, Blood Covid19	Diagnostic Test: Thrombin Generation Assay (TGA) Diagnostic Test: Thrombomodulin Modified Thrombin Generation Assay (TGA-TM)

Study Design

Study Type:

Observational

Actual Enrollment :

58 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Coagulation Assays in the Critically Ill Patient: a New Approach Using the Thrombomodulin-modified Thrombin Generation Assay (TGA-TM)

Actual Study Start Date :

Apr 15, 2020

Actual Primary Completion Date :

Feb 1, 2021

Actual Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Critical infection Patients with signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2 admitted to the ICU	Diagnostic Test: Thrombin Generation Assay (TGA) TGA via a fluorimetric module. Coagulation cascade is activated upon addition of different concentrations of tissue factor and phospholipids. The fluorogenic substrate Z-Gly-Gly-Arg-AMC (ZGGR-AMC) is cleaved by formed thrombin over time. By plotting the changes in fluorescence as a function of time (cnt/min), it depicts the "Thrombin Generation Curve" (thrombin generated - plotted against time). The area under the thrombin curve is defined as the endogenous thrombin potential (ETP). Diagnostic Test: Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) Recombinant Human Thrombomodulin (TM) is added to the conventional TGA. When recombinant TM is added, the protein C system is fully activated and therefore the ETP obtained reflects both the anti- and procoagulant factors.

Arm

Intervention/Treatment

Critical infection

Patients with signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2 admitted to the ICU

Diagnostic Test: Thrombin Generation Assay (TGA)

TGA via a fluorimetric module. Coagulation cascade is activated upon addition of different concentrations of tissue factor and phospholipids. The fluorogenic substrate Z-Gly-Gly-Arg-AMC (ZGGR-AMC) is cleaved by formed thrombin over time. By plotting the changes in fluorescence as a function of time (cnt/min), it depicts the "Thrombin Generation Curve" (thrombin generated - plotted against time). The area under the thrombin curve is defined as the endogenous thrombin potential (ETP).

Diagnostic Test: Thrombomodulin Modified Thrombin Generation Assay (TGA-TM)

Recombinant Human Thrombomodulin (TM) is added to the conventional TGA. When recombinant TM is added, the protein C system is fully activated and therefore the ETP obtained reflects both the anti- and procoagulant factors.

Outcome Measures

Primary Outcome Measures

ETP (AUC) without rhThrombomodulin (rhTM) [6 months]
nM;
ETP (AUC) with rhThrombomodulin (rhTM) [6 months]
nM;
ETP-ratio [6 months]
Ratio of endogenous thrombin potential (ETP) with rhTM to ETP without rhTM
ETP-Normalisation [6 months]
Comparison of ETP-ratios from ICU patients and ETP-ratios from citrated plasma samples from healthy donors

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Admission to ICU
Clinical signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2
Neutrophil-Lymphocyte Ratio (NLR) >3

Exclusion Criteria:

Intake of oral anticoagulants or any kind of parenteral therapeutic anticoagulation prior to ICU admission
Congenital coagulation disorder
Treatment with Prothrombin complex concentrate (F. II, VII, IX, X) or activated Prothrombin complex within past 48 hours
Treatment with recombinant factor VIIa (e.g. eptacog alfa) within past 48 hours
Treatment with recombinant protein C within past 48 hours
Active bleeding
Acute myocardial infarction
HIV infection
Chronic pancreatitis
Liver cirrhosis