The Efficacy and Safety of HCQ Plus DEX in ANA Positive ITP

Официальное название

The Efficacy and Safety of Hydroxychloroquine Plus Dexamethasone in Antinuclear Antibody-positive Patients With Primary Immune Thrombocytopenia-- The Multicenter, Randomized, Open-labled Clinical Trial

Обзор

The goal of this clinical trial is to learn if hydroxychloroquine (HCQ) plus dexamethasone (DEX) works to treat primary immune thrombocytopenia with positive anti-nuclear antibodies in adults. It will also learn about the safety of HCQ plus DEX. The main questions it aims to answer are: Does HCQ plus DEX raise the response rate in participants, compared to DEX alone? Does HCQ plus DEX prolong the response duration in participants, compared to DEX alone? What medical problems do participants have when taking HCQ plus DEX? Researchers will compare HCQ plus DEX with DEX alone to see if HCQ plus DEX works better to treat primary immune thrombocytopenia with positive anti-nuclear antibodies. Participants will: Take DEX every day for consecutive 4 days ( if platelet count does not recover higher than 30×10\^9/L after 2 weeks, take DEX every day for another consecutive 4 days) with or without HCQ twice a day for 1 year , Visit the clinic once every 1 weeks for the first 4 weeks, and once every 2-4 weeks in the following 11 months for checkups and tests, Keep a diary of their symptoms.

Подробное описание

Primary immune thrombocytopenia (Primary immune thrombocytopenia, ITP) is an acquired autoimmune hemorrhagic disease characterized with decreased peripheral platelet count and increased risk of bleeding. It has been reported that 33.3% -39.2% of ITP patients have positive antinuclear antibodies (ANA) in the course of disease.In the meantime, they do not meet the diagnostic criteria for rheumatic diseases such as lupus erythematosus(SLE). ITP patients with positive ANA are prone to relapse and chronicity. Therefore, it is necessary to explore new clinical treatments to attain longer-term remission in these patients.

Hydroxychloroquine (HCQ) has immune modulating role on a variety of immune cells.A clinical trial enrolled immune thrombocytopenia secondary to SLE, and ITP with positive anti-nuclear antibodiy (ANA) were treated with HCQ combined with glucocorticoids. The results showed an overall response rate of 60% (24 / 40), including 18 continuous complete response (CR) and 6 continuous response (R), and some patients had continued elevated platelet counts 3 months after treatment initiation. The above studies illustrate that HCQ contributes to the treatment of chronic ITP, especially as a long-term therapeutic agent with low economic burden and well-tolerated. In conclusion, it can be seen that HCQ and dexamethasone have complementary mechanism of action and complementary time window, which can be used as a combination for the treatment of ITP select.

Вмешательства

• Препарат Hydroxychloroquine Oral Tablet
  Hydroxychloroquine is taken at the dose of 0.1g / dose, twice a day for 1 year, regardless of food intake.
• Препарат Dexamethasone oral
  Dexamethasone is given at 40mg every morning after meals for 4 consecutive days( if platelet count does not recover higher than 30×10\^9/L after 2 weeks, dexamethasone is given 40mg every day for another consecutive 4 days).

Первичные конечные точки

• Overall response rate [Срок оценки: 4 weeks]

Вторичные конечные точки (8)

• Complete response rate [Срок оценки: 1 year]
• Duration of response [Срок оценки: 1 year]
• Durable response rate [Срок оценки: 1 year]
• Platelet count at each visit [Срок оценки: 1 year]
• Time to response [Срок оценки: 4 weeks]
• Response rate throughout the trial [Срок оценки: 1 year]
• WHO bleeding score [Срок оценки: 1 year]
• Adverse reaction [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Age is between 15-75 years old, and gender is unlimited.
• Before randomization, the clinical diagnosis is primary immune thrombocytopenia. The platelet count is less than 30×10\^9 / L within 1 week before enrollment, or platelet count is less than 50×10\^9 / L with bleeding symptoms within 1 week before enrollment.
• The antinuclear antibody is positive.
• Other autoantibodies (mainly including dsDNA antibodies, SSA, SSB, RNP, β 2-GP, ACA, ANCA) are negative.
• Prothrombin time does not exceed ± 3s of the normal value ranget, activated partial thrombin time is not outside normal range ± 10s; no history of coagulopathy except ITP.
• Understand the study procedures and sign the written informed consent form.

Критерии исключения

• Secondary thrombocytopenia caused by myelodysplastic syndrome, immune diseases such as systemic lupus erythematosus, early aplastic anemia, atypical reanemia, antiphospholipid syndrome, thrombotic thrombocytopenic purpura and various other causes.
• The participant has experienced any arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), or clinical symptoms and medical history indicate thrombophilia.
• Congestive heart disease, including New York Heart Association (NHYA) Grade III / IV, occurred within 3 months prior to screening, arrhythmia requiring medication or myocardial infarction, or arrhythmia known to increase the risk of thrombotic events (such as atrial fibrillation), or corrected QT interval (QTc) is longer than 450 ms, or QTc> 480 ms in paricipants with bundle branch block.
• With severe hemorrhage (intracranial hemorrhage) or coagulation dysfunction (INR and APTT> 125% upper limit of normal).
• With poorly controlled hypertension and diabetes mellitus.
• With severe digestive tract diseases affecting drug absorption.
• With serious mental illness patient.
• With liver cirrhosis or portal hypertension.
• With evidence of malignant tumor activity, or receiving anti-tumor treatment within 5 years prior to the screening.
• Addicted to alcohol or drugs.
• Having participated in other clinical trials within 3 months prior to screening.
• Having received any immunomodulatory medication for other diseases 3 months before screening.
• Having received any medication affecting platelet function ( Including but not limited to aspirin, aspirin-containing complexes, clopidogrel, salicylates, and / or non-steroidal anti-inflammatory drugs NSAIDs ) or anticoagulant therapy for over consecutive 3 days within 2 weeks before screening.
• With Glucose-6-phosphate dehydrogenase deficiency.
• With retinal or visual field changes caused by 4-aminoquinoline compounds.
• Being allergic to 4-aminoquinoline compounds.
• Having evidence of Human Immunodeficiency Virus (HIV)/ hepatitis C virus(HCV)/ hepatitis B virus(HBV) infection (HIV antibody or HCV antibody is positive, HBV surface antigen is positive, or HBV surface antigen is negative but HBV-DNA indicating viral replication.
• With a history of vaccination within 8 weeks before enrollment or scheduled for vaccination during the trial period.
• Moderate to severe anaemia (hemoglobin <90g / L).
• Glutamate transaminotransferase (ALT) or glutamate transaminase (AST) is higher than 1.5 times the upper limit of normal value (ULN), or total bilirubin or blood creatinine is higher than 1.2 times the ULN.
• Participants being pregnant or lactating, or with potential fertility, reluctance to use effective contraception within the entire trial cycle and within 28 days after the end of the trial (or within 28 days after premature withdraw).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 4 центра

• Shanghai Zhongshan Hospital — Шанхай
• Zhongshan Wusong Hospital, Fudan University — Шанхай
• Shanghai Jinshan Hospital — Шанхай
• Zhongshan Qingpu Hospital, Fudan University — Шанхай

Macau · 2 центра

• Dr. Stanley Ho Medical Foundation — Макао
• University Hospital, Macau University of Science and Technology. — Макао

Гонконг · 1 центр

• Health and Humanity Research Centre, Hongkong, China. — Гонконг

Публикации

• Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, Cuker A, Despotovic JM, George JN, Grace RF, Kuhne T, Kuter DJ, Lim W, McCrae KR, Pruitt B, Shimanek H, Vesely SK. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866. doi: 10.1182/bloodadvances.2019000966. PMID 31794604
• Khellaf M, Chabrol A, Mahevas M, Roudot-Thoraval F, Limal N, Languille L, Bierling P, Michel M, Godeau B. Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies. Am J Hematol. 2014 Feb;89(2):194-8. doi: 10.1002/ajh.23609. Epub 2013 Nov 20. PMID 24254965
• Mejdoub S, Hachicha H, Gargouri L, Feki S, Mahfoudh A, Masmoudi H. Antinuclear antibodies in children: clinical signification and diagnosis utility. Tunis Med. 2021 Octobre;99(10):980-984. PMID 35288899
• Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017 May 25;129(21):2829-2835. doi: 10.1182/blood-2017-03-754119. Epub 2017 Apr 17. PMID 28416506

Идентификаторы

NCT: NCT06479317 · ZSLCYJ202325

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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