search
Back to results

Aspirin for Prophylaxis of TTP

Primary Purpose

Thrombotic Thrombocytopenic Purpura

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Aspirin tablet
Placebo
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Thrombotic Thrombocytopenic Purpura

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Those who voluntarily signed the informed consent form and were able to comply with the study protocol.
  2. 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.
  3. 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.
  4. No stroke was detected on cranial MRI and there was no previous history of stroke.
  5. The subject is willing and able to comply with the requirements of this protocol.

Exclusion Criteria:

  1. 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
  2. Subject has increased risk for bleeding (e.g., platelet count <30,000/µL, severe coagulopathy, gastrointestinal disease)
  3. Subject has a history of drug and/or alcohol abuse within six months before enrollment.
  4. Subject has a life expectancy of fewer than three months.
  5. The investigator considers the subject unable or unwilling to cooperate with the study procedures.
  6. The subject is a family member or employee of the investigator.
  7. The patient is pregnant or breast-feeding.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Aspirin 100 mg daily

    Placebo

    Arm Description

    Once enrolled, patients will receive aspirin 100mg orally once per day

    Once enrolled, patients will receive placebo orally once per day

    Outcomes

    Primary Outcome Measures

    Number of participants with ischemic stroke
    Ischemic stroke was assessed with MRI imaging.

    Secondary Outcome Measures

    Number of participants with relapse
    Relapse refers to the presence of TTP symptoms with less than 10% ADAMTS13 activity.
    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.

    Full Information

    First Posted
    September 25, 2022
    Last Updated
    September 30, 2022
    Sponsor
    The First Affiliated Hospital of Soochow University
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05568147
    Brief Title
    Aspirin for Prophylaxis of TTP
    Official Title
    A Prospective Multicenter Clinical Study of Aspirin for Prophylaxis in Patients With Hereditary or Acquired Thrombotic Thrombocytopenic Purpura
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2022 (Anticipated)
    Primary Completion Date
    September 30, 2027 (Anticipated)
    Study Completion Date
    September 30, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    The First Affiliated Hospital of Soochow University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Thrombotic Thrombocytopenic Purpura

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Aspirin 100 mg daily
    Arm Type
    Experimental
    Arm Description
    Once enrolled, patients will receive aspirin 100mg orally once per day
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Once enrolled, patients will receive placebo orally once per day
    Intervention Type
    Drug
    Intervention Name(s)
    Aspirin tablet
    Intervention Description
    When patients are randomized into the intervention group, they will receive aspirin at the dosage of 100mg orally once every day.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    When patients are randomized into the placebo group, they will receive placebo orally once a day.
    Primary Outcome Measure Information:
    Title
    Number of participants with ischemic stroke
    Description
    Ischemic stroke was assessed with MRI imaging.
    Time Frame
    From first administration of aspirin to 3 years after treatment.
    Secondary Outcome Measure Information:
    Title
    Number of participants with relapse
    Description
    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.
    Title
    Number of participants with major bleeding
    Description
    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.

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jiaqian Qi, MD
    Phone
    8618913091817
    Email
    qijq@suda.edu.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yue Han, MD/PhD
    Phone
    15606133002
    Email
    hanyue@suda.edu.cn

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    28416507
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    11586351
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    18637802
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    30928346
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    35157766
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    27209146
    Citation
    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.
    Results Reference
    background

    Learn more about this trial

    Aspirin for Prophylaxis of TTP

    We'll reach out to this number within 24 hrs