Aspirin for Prophylaxis of TTP : A Prospective Multicenter Clinical Study of Aspirin for Prophylaxis in Patients With Hereditary or Acquired Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy. It is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and microvascular thrombosis causing neurologic and kidney abnormalities . TTP is caused by a severe deficiency of ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats, member 13) . Severe ADAMTS13 deficiency can be hereditary (hTTP), caused by biallelic pathogenic mutations of the ADAMTS13 genes, or acquired (iTTP), caused by anti-ADAMTS13 autoantibodies. Its main diagnostic criterion is a severe deficiency of ADAMTS13 (activity <10%) .hTTP is currently managed by prophylaxis with plasma infusions. Because lifetime plasma infusions are a major lifestyle burden, the current practice is to begin prophylaxis when ischemic symptoms occur. Evaluation of plasma prophylaxis by the International Hereditary Registry reported that it was not effective for decreasing the occurrence of acute episodes. When recombinant ADAMTS13 (rADAMTS13) is commercially available, prophylaxis may begin sooner and be more effective. Acute episodes of iTTP are effectively treated with ADAMTS13 replacement and immunosuppression. During remission, immunosuppression is recommended to prevent relapse if ADAMTS13 activity is <20%. If ADAMTS13 activity is less than normal but ≥20%, no treatment is recommended.Long-term follow-up of patients with hTTP has identified the frequent occurrence of stroke and kidney injury. Among 217 patients who survived infancy, 62 (29%) had had a stroke; the median age was 21 years. Long-term follow-up is also required for patients with iTTP. iTTP patients with low ADAMTS13 activity (<70%) during remission have a 28% risk for stroke. Survival of iTTP patients in remission is less than the age, race, and gender-match population. No maintenance treatment is recommended for patients with iTTP.Severe ADAMTS13 deficiency in patients with TTP allows the circulation of ultra-large multimers of von Willebrand factor (VWF). Turbulent circulation causes exposure of the VWF platelet binding site. Binding of the platelet VWF receptor, GPIbα, to the ultra-large VWF multimers is the essential initial which step for the initiation of thrombosis. A recent study documented that platelet binding to von Willebrand factor activates the platelet fibrinogen receptor, αIIbβ3, initiating platelet aggregation. Aspirin blocks αIIbβ3 activation and prevents platelet aggregation. Studies of TTP in mice have documented that aspirin decreases thrombosis. These data suggest that it may provide protection against stroke in patients with hTTP and iTTP. In addition to its potential efficacy, aspirin has minimal risks, and it is inexpensive.Aspirin is very effective for the secondary prevention of stroke. However, the therapeutic value of aspirin in TTP has not previously been studied.To improve the prognosis and survival of patients with hTTP and iTTP, we propose to conduct a prospective study to observe the efficacy and safety of aspirin in patients with the iTTP and hTTP in remission..

Medienart:	Klinische Studie

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	ClinicalTrials.gov - (2022) vom: 05. Okt. Zur Gesamtaufnahme - year:2022

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Medical Condition: Thrombotic Thrombocytopenic Purpura Phase: Phase 2, Phase 3 Purpura Purpura, Thrombocytopenic Purpura, Thrombotic Thrombocytopenic Recruitment Status: Not yet recruiting Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: October 5, 2022, Last downloaded: ClinicalTrials.gov processed this data on October 11, 2022, Last updated: October 13, 2022

Study ID:

NCT05568147 SOOCHOW-HY-2022-11

Veröffentlichungen zur Studie:

Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017 May 25;129(21):2836-2846. doi: 10.1182/blood-2016-10-709857. Epub 2017 Apr 17. Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001 Oct 4;413(6855):488-94. doi: 10.1038/35097008. Scully M, Yarranton H, Liesner R, Cavenagh J, Hunt B, Benjamin S, Bevan D, Mackie I, Machin S. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol. 2008 Sep;142(5):819-26. doi: 10.1111/j.1365-2141.2008.07276.x. Epub 2008 Jul 8. Tsai HM. Thrombotic Thrombocytopenic Purpura: Beyond Empiricism and Plasma Exchange. Am J Med. 2019 Sep;132(9):1032-1037. doi: 10.1016/j.amjmed.2019.03.009. Epub 2019 Mar 28. Shao B, Hoover C, Shi H, Kondo Y, Lee RH, Chen J, Shan X, Song J, McDaniel JM, Zhou M, McGee S, Vanhoorelbeke K, Bergmeier W, Lopez JA, George JN, Xia L. Deletion of platelet CLEC-2 decreases GPIbalpha-mediated integrin alphaIIbbeta3 activation and decreases thrombosis in TTP. Blood. 2022 Apr 21;139(16):2523-2533. doi: 10.1182/blood.2021012896. Rothwell PM, Algra A, Chen Z, Diener HC, Norrving B, Mehta Z. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet. 2016 Jul 23;388(10042):365-375. doi: 10.1016/S0140-6736(16)30468-8. Epub 2016 May 18.

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PPN (Katalog-ID):	CTG008695105