Clinical trial NCT05128760: Impact of Antiphospholipid Antibodies on Thrombin Generation During Sars-CoV2 Infection (TACIT2 Study)
Official title: Impact of Antiphospholipid Antibodies on Thrombin Generation During Sars-CoV2 Infection.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Antiphospholipid Syndrome
COVID-19
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2021-11-22
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Five groups of subjects will be enrolled in the study :

1. patients hospitalized for à COVID-19 with aPL
2. patients hospitalized for à COVID-19 without aPL
3. patients with APS
4. as control, patients with acute venous thromboembolism disease
5. as control, healthy volunteers.

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Frequency of activated protein C resistance and comparison between groups
timeFrame: at inclusion
Secondary outcomes:
measure: frequency of positivity of each aPL test and comparison between groups
timeFrame: at inclusion
measure: concentration of leucocytes activation markers and comparison between groups
timeFrame: at inclusion
measure: frequency of persistent aPL test positivity and comparison between groups
timeFrame: at three month
Other outcomes:
Locations:
city: Nancy
country: France
facility: Virginie Dufrost
Study officials:
affiliation: CHRU of Nancy
name: Denis G Wahl, MD, PhD
role: STUDY_DIRECTOR
affiliation: CHRU of Nancy
name: Stéphane Zuily, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU of Nancy
name: Virginie Dufrost, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. No abstract available.
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 beta2-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.
citation: Yalavarthi S, Gould TJ, Rao AN, Mazza LF, Morris AE, Nunez-Alvarez C, Hernandez-Ramirez 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.
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.