Determination of Fibrin Activity in Plasma on STA-R® Prototype (FAST)

The purpose of the study is to give the proof of concept of the Fibrin structure assay on STA-R® prototype. It aims to identify the parameters which discriminate the pathologic from the normal population. Secondary objectives are to determine the precision of the assay, to record the Fibrin activity, comparatively with thromboelastography on TEG®, in a coagulation activation assay and in a coagulation-lysis assay.

Study Overview

• Status: Completed
• Conditions: Blood Coagulation Disorders; Hemorrhagic Disorders; Trauma; Thrombotic Disorders
• Intervention / Treatment: Other: Routine hemostasis tests; Other: Fibrin structure (FS); Other: Thromboelastography (TEG); Other: Specialized hemostasis tests

Detailed Description

Background. Fibers thickness of the fibrin clot plays an important role on the clot stability and its resistance to the fibrinolysis. The innovative concept, based on the relationship between light spectrum through the fibrin clot and its fiber nanostructure (C.Dassi et al, ISTH 15ABS-3593), thanks to a multi-wavelength STA-R® prototype, was simplified by using a coag-lysis assay (An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: SSC communication ; Pieters et al. ; JTH 2018) Preliminary results suggest that this new automated FS method provides new data on clot analysis and could be a useful tool in clinical practice in the management of hemostasis disorders. This study is extended to begining of march 2019.

Main objective. This study aims to determine the precision, the normal range of the FS method in comparison with Thromboelastography on TEG® and discriminate patients from healthy volunteers (HV).

Recruitment. 200 healthy volunteers without any known coagulation troubles, enrolled during coagulation testing or blood donation.

50 hospitalized patients or patients from consultations, without ongoing treatment (particularly anticoagulant treatment), with a normal hemostasis screening (Prothombin Time, Activated Partial Prothombine Time and Fibrinogen Level).

650 hospitalized patients for any pathology known and able to induce a increase or a decrease of the fibrinogen level, mainly from trauma patients and enrolled during coagulation testing.

The study is conducted in compliance with French regulation after ethics approval.

FS Assays. The FS determinations on STA-R® prototype and those on TEG® will be realized with fresh plasmas and whole blood samples respectively at the Hôpital d'Instruction des armées Percy. The screening tests (PT, APTT, and Fibrinogen) on STA-R® Evolution and the measurement of FS on a second STA-R® prototype will be performed with frozen plasmas at STAGO laboratory.

Statistical analysis of results. A statistical analysis will determine the most relevant parameters in the discrimination of the pathologic population from the normal population, and the quality control precision. Then, statistical analysis will compare STA-R® prototype method to the TEG® method to point out the most populations discriminating method.

• Study Type: Observational
• Enrollment (Actual): 913

Contacts and Locations

Study Locations

• France
  • Clamart, France, 92140
    • Hôpital d'Instruction des armées Percy - Laboratoire d'Hématologie

Participation Criteria

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

Healthy volonteers from Centre de Transfusion des Armées (CTSA) and from Centre Principal d'Expertise Médicale du Personnel Navigant (CPEMPN).

Percy hospital patients from at least: Emergency Unit (EU), Intensive Care Unit (ICU), Burnt Treatment Center (BTC), Hematology department.

Description

Inclusion Criteria:

• Patients and healthy volunteers with non-opposition to participate in the evaluation
• Healthy volunteers : from 18 years to 70 years
• Patients : minimum age limit 18 years - no maximum age limit

Exclusion Criteria:

• Healthy volonteers with ongoing treatment
• Healthy volonteers with abnormal hemostasis results

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy volunteers (HV); HV without any known treatment, without any coagulation trouble and with normal hemostasis results. FS and TEG will be processed to define the most relevant parameters for normal range and the correlation between both assays. Tests performed on HV : Routine hemostasis tests; Fibrin structure (FS); Thromboelastography (TEG); Specialized hemostasis tests	Other: Routine hemostasis tests; Prothrombin Time (PT),Thrombin Time (TT), Activated Partial Thromboplastin Time (APTT), Fibrinogen, D-Dimers; Other: Fibrin structure (FS); FS will be determined on STA-R® prototype at Percy and at Stago; Other: Thromboelastography (TEG); Thromboelastography will be processed on TEG® at Percy; Other: Specialized hemostasis tests; Coagulation factors
Patients without coagulation disorder; Hospitalized patients without coagulation disorder or abnormal hemostasis and hematological results and witout ongoing treatment (mainly anticoagulant treatment). FS and TEG will be processed to determine the most relevant parameters to discriminate patients from normal range and the correlation between assays. Tests performed on patients : Routine hemostasis tests; Fibrin structure (FS); Thromboelastography (TEG)	Other: Routine hemostasis tests; Prothrombin Time (PT),Thrombin Time (TT), Activated Partial Thromboplastin Time (APTT), Fibrinogen, D-Dimers; Other: Fibrin structure (FS); FS will be determined on STA-R® prototype at Percy and at Stago; Other: Thromboelastography (TEG); Thromboelastography will be processed on TEG® at Percy
Patients with coagulation disorders; Hospitalized patients with coagulation disorders, mainly trauma patients or abnormal hemostasis and hematological results, mainly decreased fibrinogen level . FS and TEG will be processed to determine the most relevant parameters to discriminate patients from normal range and the correlation between assays. Tests performed on patients : Routine hemostasis tests; Fibrin structure (FS); Thromboelastography (TEG)	Other: Routine hemostasis tests; Prothrombin Time (PT),Thrombin Time (TT), Activated Partial Thromboplastin Time (APTT), Fibrinogen, D-Dimers; Other: Fibrin structure (FS); FS will be determined on STA-R® prototype at Percy and at Stago; Other: Thromboelastography (TEG); Thromboelastography will be processed on TEG® at Percy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamic evolution of the number of protofibrils	Evolution of the Fibrin structure (FS) measurement will be performed on two plasma groups, the first group is constituted with fresh healthy volunteers and the second one with fresh patients. Coagulolytic balance will be measured with FS method. In addition, a normal range will be determined on fresh healthy volunteers without any known coagulation troubles. Fibrin structure is processed to determine the most relevant parameters to discriminate patients from normal range and the correlation between assays.	12 months
Dynamic evolution of fibrin formation	Evolution of the optical density measurement and calculating the fibrinogen level and coagulolytic balance	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboelastography measurement on TEG 5000	Thromboelastography will be performed on two plasma groups, the first group is constituted with fresh healthy volunteers and the second one with fresh patients. Viscoelastic clot parameters will be determined on TEG 5000. Thromboelastography is processed to determine the most relevant parameters to discriminate patients from normal range and the correlation between assays.	12 months
Prothrombin Time (PT)	These assays will be performed at Stago on all samples from healthy volunteers (HV) and patients to allow the biological confirmation of normal samples from HV group. In case of one abnormal result, the sample is considered as not relevant for the normal range determination of Fibrin Structure measurement and will be discarded from HV group.	12 months
Thrombin Time (TT)	These assays will be performed at Stago on all samples from healthy volunteers (HV) and patients to allow the biological confirmation of normal samples from HV group. In case of one abnormal result, the sample is considered as not relevant for the normal range determination of Fibrin Structure measurement and will be discarded from HV group.	12 months
Activated Partial Thromboplastin Time (APTT)	These assays will be performed at Stago on all samples from healthy volunteers (HV) and patients to allow the biological confirmation of normal samples from HV group. In case of one abnormal result, the sample is considered as not relevant for the normal range determination of Fibrin Structure measurement and will be discarded from HV group.	12 months
Fibrinogen	These assays will be performed at Stago on all samples from healthy volunteers (HV) and patients to allow the biological confirmation of normal samples from HV group. In case of one abnormal result, the sample is considered as not relevant for the normal range determination of Fibrin Structure measurement and will be discarded from HV group.	12 months
D-Dimers	These assays will be performed at Stago on all samples from healthy volunteers (HV) and patients to allow the biological confirmation of normal samples from HV group. In case of one abnormal result, the sample is considered as not relevant for the normal range determination of Fibrin Structure measurement and will be discarded from HV group.	12 months

Collaborators and Investigators

• Sponsor: Diagnostica Stago R&D
• Collaborators: Hôpital d'Instruction des armées Percy
• Investigators: Principal Investigator: Vincent Foissaud, M D, Hopital D'Instruction Des Armees Percy; Study Director: Geneviève Contant, Ph D, Diagnostica Stago SAS

Publications and helpful links

General Publications

• Yeromonahos C, Polack B, Caton F. Nanostructure of the fibrin clot. Biophys J. 2010 Oct 6;99(7):2018-27. doi: 10.1016/j.bpj.2010.04.059.
• Zabczyk M, Undas A. Plasma fibrin clot structure and thromboembolism: clinical implications. Pol Arch Intern Med. 2017 Dec 22;127(12):873-881. doi: 10.20452/pamw.4165. Epub 2017 Dec 11.
• Pieters M, Philippou H, Undas A, de Lange Z, Rijken DC, Mutch NJ; Subcommittee on Factor XIII and Fibrinogen, and the Subcommittee on Fibrinolysis. An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: communication from the SSC of the ISTH. J Thromb Haemost. 2018 May;16(5):1007-1012. doi: 10.1111/jth.14002. Epub 2018 Apr 15. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: August 2, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Fibrinolysis; Thromboelastography; Fibrin structure; Coag-Lysis assay; Fibrin formation; TEG 5000; TEG 6S; Coagulo-lytic balance; Normal range
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Embolism and Thrombosis; Hemostatic Disorders; Blood Coagulation Disorders; Disease; Thrombosis; Hemorrhagic Disorders; Coagulants; Hemostatics
• Other Study ID Numbers: FAST STUDY 2016-A00869-42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No