Impact of Antiphospholipid Antibodies on Thrombin Generation During Sars-CoV2 Infection (TACIT2 Study)

COVID-19 Clinical Trial

— TACIT2  

Official title:

Impact of Antiphospholipid Antibodies on Thrombin Generation During Sars-CoV2 Infection.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05128760
• Other study ID #: 2021-A00244-37
• Status: Not yet recruiting
• Start date: January 1, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: November 2021
• Source: Central Hospital, Nancy, France
• Contact: Virginie DUFROST, MD
• Phone: +33383157828
• Email: v.dufrost[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Context: Until 70% of thrombotic event are reported during Sars-CoV2 infection. Antiphospholipid antibodies (aPL) tests are often positive. We aim to determine if aPL positivity is involved in thrombose of Sars-CoV2 infection investigating the effect of aPL on thrombin generation (TG) and leucocyte pathway activation (neutrophils extracellular traps (NETs) and activation of triggering receptor expressed on myeloid cells 1 (TREM-1)). Method: We will compare plasma from five groups of subjects: patients with antiphospholipid syndrome (APS) and patients hospitalized for Sars-CoV-2 infection with or without aPL, and as control, patients with acute venous thromboembolism event and healthy volunteers. For each subject, we will analyze aPL, activated protein C (APC) resistance measured by TG and leukocytes markers as circulating neutrophils extracellular traps (NETs) and soluble triggering receptor expressed on myeloid cells one (sTREM-1). We will control aPL test at three month and analyze their persistent positivity and association with thrombotic event. Results: we hypothesize that patients with COVID-19 and aPL will have a similar aPL and level of APS resistance that patients with APS. Also, we think that circulating NETs and sTREM-1 levels will be more important in patients with COVID-19 with aPL than patients without aPL and similar in patients with COVID-19 and aPL and patients with APS. Conclusion: our study will be the first to analyze the potential role of aPL on APC resistance measured by TG and neutrophil activation in COVID-19.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 161
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient receiving a comprehensive information about the study, and not opposed to participate

+ one criterion among :

• patient hospitalized fo a COVID-19
• Patient with known APS
• Patients hospitalized for an acute venous thromboembolism event aPL positivity or COVID-19
• healthy volunteers

Exclusion Criteria:

• For all participants : pregnancy, age below 18 years-old, absence of written informed consent , autoimmune or inflammatory disease except antiphospholipid syndrome
• For patients with COVID-19: previous aPL positivity (before COVID-19 infection)
• For patients with APS: previous symptomatic COVID-19 infection
• For patients control with acute venous thromboembolism event: previous symptomatic COVID-19 infection, infection or inflammatory disease in flare at the time of thromboembolism event, known aPL positivity
• For Healthy volunteers: history of thrombosis (venous, arterial or small vessels), previous symptomatic COVID-19 infection, infection or inflammatory disease in flare at the time of inclusion, known aPL positivity

Related Conditions & MeSH terms

• Antiphospholipid Syndrome
• COVID-19

Intervention

Diagnostic Test:
• characterization of aPL
characterization of aPL profile, GT profile and leukocytes activations markers (NETs, TREM-1)

Locations

Country	Name	City	State
France	Virginie Dufrost	Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Country where clinical trial is conducted

France, 

References & Publications (4)

Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, MacDonald V, Green L, Sivapalaratnam S, Pasi KJ, MacCallum P. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020 Jul 16;383(3):288-290. doi: 10.1056/NEJMc2013656. Epub 2020 May 5. — View Citation

Edel Y, Kliminski V, Pokroy-Shapira E, Oren S, Dortort Lazar A, Pri-Paz Basson Y, Egbaria M, Molad Y. Elevated plasma level of soluble triggering receptor expressed on myeloid cells-1 is associated with inflammation activity and is a potential biomarker of thrombosis in primary antiphospholipid syndrome. Arthritis Res Ther. 2019 Jan 7;21(1):10. doi: 10.1186/s13075-018-1779-5. — View Citation

Yalavarthi S, Gould TJ, Rao AN, Mazza LF, Morris AE, Núñez-Álvarez C, Hernández-Ramírez D, Bockenstedt PL, Liaw PC, Cabral AR, Knight JS. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 2015 Nov;67(11):2990-3003. doi: 10.1002/art.39247. — View Citation

Zuily S, de Laat B, Guillemin F, Kelchtermans H, Magy-Bertrand N, Desmurs-Clavel H, Lambert M, Poindron V, de Maistre E, Dufrost V, Risse J, Shums Z, Norman GL, de Groot PG, Lacolley P, Lecompte T, Regnault V, Wahl D. Anti-Domain I ß2-Glycoprotein I Antibodies and Activated Protein C Resistance Predict Thrombosis in Antiphospholipid Syndrome: TAC(I)T Study. J Appl Lab Med. 2020 Nov 1;5(6):1242-1252. doi: 10.1093/jalm/jfaa072. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of activated protein C resistance and comparison between groups		at inclusion
Secondary	frequency of positivity of each aPL test and comparison between groups		at inclusion
Secondary	concentration of leucocytes activation markers and comparison between groups		at inclusion
Secondary	frequency of persistent aPL test positivity and comparison between groups		at three month