Influence of Edoxaban on Coagulability and Thrombin Generation: An in Vitro Study Focusing on Thrombelastography

Heart Failure Clinical Trial

Official title: Influence of Edoxaban on Coagulability and Thrombin Generation: An in Vitro Study Focusing on Thrombelastography

Status Recruiting

Clinical Trial Summary

The influence of different doses of edoxaban on physical characteristics of the clot and thrombin generation kinetics in blood samples will be studied by in vitro spiking of blood samples collected from patients treated for heart failure (with and without hypercoagulability) and from healthy volunteers (with and without hypercoagulability). This in vitro experiment will help us to:

(i) detect qualitative anticlotting properties of edoxaban. (ii) quantify the anticlotting properties of edoxaban.

Clinical Trial Description

Experimental protocol

1. On the day of experiment blood samples will be collected in 3.2% citrate tubes.

2. One citrated blood tube will be centrifuged to collect plasma for biomarker measurements (C-reactive protein (CRP), fibrinogen, von Willebrand factor (vWF), interleukin (IL)-6, p-selectin, plasminogen activator inhibitor (PAI)-1, matrix metalloproteinase (MMP)-9).

3. Blood samples will be incubated with different concentrations of edoxaban (no edoxaban, subtherapeutic range - 30 nM, therapeutic range -300 nM, and supratherapeutic range- 900 nM) (3).

A) Cora® Hemostasis Analyzer System (Cora®) will be used to assess qualitative and quantitative assessment of the hemostatic properties of a blood sample in the presence or absence of edoxaban. The CORA is an integrated computer module with Ethernet connection capability and provides continuous resonance-frequency viscoelasticity measurements using a disposable four-channel microfluidic cartridge to determine simultaneous maximal platelet-fibrin clot strength, fibrin clot strength, and response to antiplatelet agents or anticoagulants. The cartridge has four channels - citrated Kaolin (CK) channel that measures platelet-fibrin clot strength, anti-Xa channel, DTI channel and FFC channel that measures contribution of functional fibrinogen.

In addition, using the V-curve software, the following parameters of thrombin generation kinetics will be evaluated from the CK channel- R - Period of time of latency from the time that the blood was placed in the TEG® analyzer until the initial fibrin formation. This represents the enzymatic portion of coagulation.

K - K time is a measure of the speed to reach a certain level of clot strength. This represents clot kinetics.

alpha - measures the rapidity of fibrin build-up and cross-linking (clot strengthening). This represents fibrinogen level.

MA - Maximum Amplitude is a direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa and represents the ultimate strength of the fibrin clot. This represents platelet function/aggregation.

TMRTG - Time to maximum rate of thrombus generation. MRTG - Maximum rate of thrombus generation. TG - Total thrombus generated. TMRL - Time to maximum rate of lysis MRL - Maximum rate of lysis L - Total lysis D - Delta is the difference between R time and the time of initial split point (SP, mins) of the TEG tracing (R - SP), representing the time interval of greatest clot growth secondary to peak thrombin generation.

B) Calibrated Automated Thrombogram® (CAT) System: Lag time, peak thrombin production, mean velocity rate index and endogenous thrombin potential (ETP) will be assessed by calibrated automated thrombogram in platelet poor plasma (Thrombinoscope by Stago). ;

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Heart Failure

• NCT number: NCT02448901
• Study type: Observational
• Source: LifeBridge Health
• Contact: Kevin P Bliden, BS, MBA
• Phone: 410-601-4795
• Email: kbliden@lifebridgehealth.org
• Status: Recruiting
• Phase: N/A
• Start date: April 2015
• Completion date: March 2016