The Combination of Oral All-trans Retinoic Acid and Danazol vs Danazol as Second-line Treatment in Adult Immune Thrombocytopenia: a Multicenter, Randomized, Open-label Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 5
- 主要终点
- the sustained platelet response at the 12-month follow-up
研究概览
简要总结
Randomized, open-label, multicentre study to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.
详细描述
Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients achieve remission from first-line therapies. However, the underlying mechanism of corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haematopoiesis, making it a possible treatment option.
A multicentre prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were randomized to ATRA+danazol and danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study, in order to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
- •Platelet count of less than 30×109/L at enrolment
- •Patients who did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation.
- •18 years older.
排除标准
- •Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus)
- •congestive heart failure
- •severe arrhythmia
- •nursing or pregnant women
- •aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria
- •creatinine or serum bilirubin levels each 1•5 times or more than the normal range
- •active or previous malignancy
- •Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.
研究组 & 干预措施
All-trans retinoic acid ＆Danazol
Danazol 400mg po and ATRA 10mg bid po
干预措施: All-trans retinoic acid (Drug)
All-trans retinoic acid ＆Danazol
Danazol 400mg po and ATRA 10mg bid po
干预措施: Danazol (Drug)
Danazol
Danazol 400mg po
干预措施: Danazol (Drug)
结局指标
主要结局
the sustained platelet response at the 12-month follow-up
时间窗: From the start of study treatment (Day 1) up to the end of Month 12
The number of participants (responders) with platelet count \>=30x10\^9/L and at least a 2-fold increase in the baseline count (PR) or a platelet count \>=100x10\^9/L (CR) and the absence of bleeding, without rescue medication at 12-month follow-up.
次要结局
- overall response(From the start of study treatment (Day 1) up to the end of Month 12)
- primary response rate at 4 weeks(From the start of study treatment (Day 1) up to week 4 of treatment)
- primary response rate at 8 weeks(From the start of study treatment (Day 1) up to week 8 of treatment)
- time to response(From the start of study treatment (Day 1) up to the end of month 12)
- duration of response(From the start of study treatment (Day 1) up to the end of month 12)
- reduction in bleeding symptoms(From the start of study treatment (Day 1) up to the end of month 12)
- safety(From the start of study treatment (Day 1) up to the end of follow-up)
研究者
Xiao-hui Zhang
Professor
Peking University People's Hospital