- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05568147
Aspirin for Prophylaxis of TTP
A Prospective Multicenter Clinical Study of Aspirin for Prophylaxis in Patients With Hereditary or Acquired Thrombotic Thrombocytopenic Purpura
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Jiaqian Qi, MD
- Phone Number: 8618913091817
- Email: qijq@suda.edu.cn
Study Contact Backup
- Name: Yue Han, MD/PhD
- Phone Number: 15606133002
- Email: hanyue@suda.edu.cn
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Those who voluntarily signed the informed consent form and were able to comply with the study protocol.
- Subjects diagnosed with severe ADAMTS13 deficiency, defined as ADAMTS13 activity <10%, documented in the patient's medical history or at screening. Note: In patients receiving fresh frozen plasma (FFP) or other prophylactic treatments containing ADAMTS13 products, plasma ADAMTS13 activity levels at screening may exceed 10%. hTTP will be documented by ADAMTS13 activity <10% and biallelic pathogenic ADAMTS13 mutations. Patients with hTTP may be asymptomatic. iTTP will be diagnosed by ADAMTS13 activity <10% and the presence of an ADAMTS13 activity inhibitor (or comparable test for anti-ADAMTS13 antibodies). The diagnosis of hTTP may be supported by the recovery of ADAMTS13 activity to >10% during clinical remission.
- Subjects do not exhibit any severe symptoms of TTP at the time of screening. At screening, patients with mild but stable laboratory abnormalities (LDH not higher than three times the upper limit of normal; platelet count not less than 100,000/microliter) are eligible for enrollment.
- No stroke was detected on cranial MRI and there was no previous history of stroke.
- The subject is willing and able to comply with the requirements of this protocol.
Exclusion Criteria:
- Subject has a history of significant neurological events, such as a major stroke, indicating that a relapse may have serious consequences, as judged by the investigator
- Subject has increased risk for bleeding (e.g., platelet count <30,000/µL, severe coagulopathy, gastrointestinal disease)
- Subject has a history of drug and/or alcohol abuse within six months before enrollment.
- Subject has a life expectancy of fewer than three months.
- The investigator considers the subject unable or unwilling to cooperate with the study procedures.
- The subject is a family member or employee of the investigator.
- The patient is pregnant or breast-feeding.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Aspirin 100 mg daily
Once enrolled, patients will receive aspirin 100mg orally once per day
|
When patients are randomized into the intervention group, they will receive aspirin at the dosage of 100mg orally once every day.
|
Placebo Comparator: Placebo
Once enrolled, patients will receive placebo orally once per day
|
When patients are randomized into the placebo group, they will receive placebo orally once a day.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with ischemic stroke
Time Frame: From first administration of aspirin to 3 years after treatment.
|
Ischemic stroke was assessed with MRI imaging.
|
From first administration of aspirin to 3 years after treatment.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with relapse
Time Frame: From first administration of aspirin to 3 years after treatment.
|
Relapse refers to the presence of TTP symptoms with less than 10% ADAMTS13 activity.
|
From first administration of aspirin to 3 years after treatment.
|
Number of participants with major bleeding
Time Frame: From first administration of aspirin to 3 years after treatment.
|
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.
|
From first administration of aspirin to 3 years after treatment.
|
Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Hematologic Diseases
- Hemorrhage
- Blood Coagulation Disorders
- Skin Manifestations
- Thrombocytopenia
- Blood Platelet Disorders
- Thrombophilia
- Thrombotic Microangiopathies
- Purpura
- Purpura, Thrombocytopenic
- Purpura, Thrombotic Thrombocytopenic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Aspirin
Other Study ID Numbers
- SOOCHOW-HY-2022-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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