Immunomodulation in Young and Midlife Adults With Newly Diagnosed Primary Immune Thrombocytopenia (ITP): A Randomized Open Label Trial With High-dose Dexamethasone Versus Eltrombopag and High-dose Dexamethasone
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 6
- 主要终点
- Change in percentual T-regulatory cells (Tregs)
研究概览
简要总结
The study aims to investigate immunomodulatory effects of eltrombopag combined with dexamethasone in young and midlife adult patients with newly diagnosed primary Immune thrombocytopenia (ITP).
详细描述
The randomized open lable study aims to investigate immunomodulatory effects of eltrombopag combined with dexamethasone in young and midlife adult patients with newly diagnosed primary ITP. Treatment protocol will be HD-DXM (40 mg PO, day 1-4) with or without eltrombopag (25-50 mg PO, day 5-140) on an outpatient basis. Immunological investigations will be performed before start of treatment and then on week 3, 20 (end of therapy) and 30.
- Intervention phase:
Medical history and physical examination including assessment of severe bleeding every week until week 4, every second week until week 20. Complete blood count every week until week 10. For the adjustment of the Thrombopoietin receptor agonist (TPO-RA) dose - every second week until week 20. Immunologic panel at the beginning and at week 3 and 20. 2. Follow-up:
Three clinical visits are scheduled in the follow-up including a complete blood count: at week 22, 24 and 30. Immunologic panel will be done at week 30 (end of study).
High-dose dexamethasone (HD-DXM) will be administered orally (40 mg) from day 1-4, followed by Arm 1 or 2 (1:1 randomization).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The laboratory team will be kept blinded regarding information about response or non-response of patients.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent as documented by signature
- •Newly diagnosed primary ITP according to the definition of Rodeghiero et al. and a risk of platelet count of <30x109/l or risk of severe bleeding
- •First-line therapy maximum for 1 week prior to enrolment
- •Bleeding severity and quality of life are neither an inclusion nor an exclusion criterion.
排除标准
- •Patients previously treated for ITP more than 7 days prior to enrolment (e.g. Steroid, intravenous immunoglobulin (IVIG), platelet infusion)
- •Patients treated with second-line drugs prior to enrolment
- •Life-threatening bleeding (and inability to sign informed consent)
- •Secondary ITP
- •Positive family history for ITP
- •Presence or history of autoimmune disease as judged by the investigator
- •Hepatosplenomegaly in the clinical examination
- •Relevant hepatic disease as judged by the investigator
- •Presence or history of thromboembolic disease
- •Patients with splenectomy
- •Women who are pregnant or breast feeding
- •Intention to become pregnant during the course of the study
- •Lack of safe double contraception
- •Any vaccination 2 weeks prior start of the study
- •Immunsuppressive and antiplatelet drugs
- •Known or suspected non-compliance, drug or alcohol abuse
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, incompetence to judge
- •Participation in another study with investigational drug within the 30 days preceding and during the present study
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
研究组 & 干预措施
Study Arm
HD-DXM will be administered orally (40 mg) from day 1-4, followed by Arm 2:
The subjects in the experimental arm will be treated with eltrombopag:
Eltrombopag (Revolade®), 50 mg PO, from day 5-140. Tapering over 1 week (week 21) from day 141-148 with 50 mg every second day. Eltrombopag will be administered on a starting dose of 50mg. After the end of treatment a clinical and laboratory observation follow-up period until week 30 follows.
干预措施: Eltrombopag (Revolade®) (Drug)
结局指标
主要结局
Change in percentual T-regulatory cells (Tregs)
时间窗: before (Tregs/CD4), at week 3 and at the end of the treatment (week 20)
Assessment of the percentage of Tregs (Tregs/CD4) in the study arm compared to the standard arm. The Tregs will be defined as CD4+CD25+ CD127+ in the fluorescence-activated cell sorting (FACS).
次要结局
- Platelet response to eltrombopag(at baseline and weeks 6, 20 and 30)
- Change in Th1/Th2 balance(at baseline and weeks 3, 20 and 30)
- Clinical response to eltrombopag therapy(trial duration (baseline to week 30))