Aspirin for Prophylaxis of TTP

NCT05568147 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SOOCHOW-HY-2022-11
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Thrombotic Thrombocytopenic Purpura

Outcome Measures

Primary Outcomes (1)

• Number of participants with ischemic stroke

  Ischemic stroke was assessed with MRI imaging.

  From first administration of aspirin to 3 years after treatment.

Secondary Outcomes (2)

• Number of participants with relapse

  From first administration of aspirin to 3 years after treatment.

• Number of participants with major bleeding

  From first administration of aspirin to 3 years after treatment.

Study Arms (2)

Aspirin 100 mg daily

EXPERIMENTAL

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

Drug: Aspirin tablet

Placebo

PLACEBO COMPARATOR

Once enrolled, patients will receive placebo orally once per day

Drug: Placebo

Interventions

Aspirin tablet DRUG

When patients are randomized into the intervention group, they will receive aspirin at the dosage of 100mg orally once every day.

Aspirin 100 mg daily

Placebo DRUG

When patients are randomized into the placebo group, they will receive placebo orally once a day.

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Related Publications (6)

• 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.

  PMID: 28416507 BACKGROUND

• 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.

  PMID: 11586351 BACKGROUND

• 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.

  PMID: 18637802 BACKGROUND

• 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.

  PMID: 30928346 BACKGROUND

• 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.

  PMID: 35157766 BACKGROUND

• 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.

  PMID: 27209146 BACKGROUND

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Jiaqian Qi, MD

CONTACT

8618913091817; qijq@suda.edu.cn

Yue Han, MD/PhD

CONTACT

15606133002; hanyue@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: vice director hematologic department

Study Record Dates

• First Submitted: September 25, 2022
• First Posted: October 5, 2022
• Study Start: October 1, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: October 5, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share