A Phase 2/3 interventional study of Aspirin tablet and Placebo in Thrombotic Thrombocytopenic Purpura, sponsored by The First Affiliated Hospital of Soochow University. Not yet recruiting. Per ClinicalTrials.gov, last updated 2022-10-05.
Sponsored by The First Affiliated Hospital of Soochow University · Phase 2/3, Interventional, and Prevention
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic hemolytic anemia, and microvascular thrombosis causing neurological and renal abnormalities; it is associated with massive depletion of platelets in the microvasculature to form microthrombi1 . Long-term follow-up of patients with congenital TTP (cTTP) revealed frequent strokes and renal injury. Of 217 surviving patients, 62 (29%) had a stroke; the median age was 21 years. iTTP patients also require long-term follow-up. iTTP patients with low ADAMTS13 activity (\<70%) in remission have a 28% risk of stroke. Survival rates of iTTP patients in remission were lower than those of age-, race-, and sex-matched populations. In terms of stable treatment, maintenance therapy is not recommended for patients with iTTP. Previous studies have shown that aspirin may be able to prevent stroke complications in patients with cTTP and iTTP. In addition to its potential efficacy, the risks of aspirin are small and inexpensive. Aspirin is very effective in secondary prevention of stroke 6. However, the therapeutic value of aspirin in TTP has not been studied previously. To improve the prognosis and survival of patients with cTTP and iTTP, we propose to conduct a prospective study to observe the efficacy and safety of aspirin in patients with cTTP and iTTP in remission.
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.
263 studies on the registry are indexed under Purpura; 27 are open to participants now.
This study's planned enrollment of 100 is above the median of 50 across 171 interventional studies indexed under Purpura.
Browse Purpura studies →The First Affiliated Hospital of Soochow University is the lead sponsor of 252 studies on the registry; 148 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Once enrolled, patients will receive aspirin 100mg orally once per day
Drug: Aspirin tablet
Once enrolled, patients will receive placebo orally once per day
Drug: Placebo
When patients are randomized into the intervention group, they will receive aspirin at the dosage of 100mg orally once every day.
When patients are randomized into the placebo group, they will receive placebo orally once a day.
Number of participants with ischemic stroke
Ischemic stroke was assessed with MRI imaging.
Time frame: From first administration of aspirin to 3 years after treatment.
Number of participants with relapse
Relapse refers to the presence of TTP symptoms with less than 10% ADAMTS13 activity.
Time frame: From first administration of aspirin to 3 years after treatment.
Number of participants with major bleeding
Major bleedings refer to the heavy bleedings of the mains organs of the body, usually include intracranial bleeding and gastrointestinal bleeding et al.. Brain computed tomography and gastrointestinal endoscope are the common approaches for diagnosing major bleedings.
Time frame: From first administration of aspirin to 3 years after treatment.
No study locations are listed for this record.
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Plan to share: No
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The First Affiliated Hospital of Soochow University