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

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04356144
• Other study ID #: TGA-TM-Critical-2019
• Status: Completed
• Start date: April 15, 2020
• Est. completion date: February 1, 2021

Study information

• Verified date: March 2021
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Coagulation Disorder, Blood
• Covid19
• Critical Illness
• Disseminated Intravascular Coagulation
• Hemostatic Disorders
• Infection
• Sars-CoV2
• Viral Infection
• Virus Diseases

Intervention

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).
• 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.

Locations

Country	Name	City	State
Austria	Medical University Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Medical Scientific Fund of the Mayor of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ETP (AUC) without rhThrombomodulin (rhTM)	nM;	6 months
Primary	ETP (AUC) with rhThrombomodulin (rhTM)	nM;	6 months
Primary	ETP-ratio	Ratio of endogenous thrombin potential (ETP) with rhTM to ETP without rhTM	6 months
Primary	ETP-Normalisation	Comparison of ETP-ratios from ICU patients and ETP-ratios from citrated plasma samples from healthy donors	6 months