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

March 22, 2021 updated by: Lukas Infanger, Medical University of Vienna

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

58

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medical University Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

60 critically ill patients with signs of infection with SARS-CoV2 or proven infection with SARS-CoV-2 admitted to Intensive Care Units (ICU).

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Collaborators

Medical Scientific Fund of the Mayor of Vienna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2020

Primary Completion (Actual)

February 1, 2021

Study Completion (Actual)

February 1, 2021

Study Registration Dates

First Submitted

April 15, 2020

First Submitted That Met QC Criteria

April 18, 2020

First Posted (Actual)

April 22, 2020

Study Record Updates

Last Update Posted (Actual)

March 23, 2021

Last Update Submitted That Met QC Criteria

March 22, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TGA-TM-Critical-2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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