Eltrombopag Plus Diacerein vs Eltrombopag in Adult Primary Immune Thrombocytopenia: a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Initial response at Day 15
研究概览
简要总结
Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with low platelet count. As the first choice of the second-line treatment of ITP, thrombopoietin receptor agonist (TPO-RA) enable long-term remission in 50% to 60% of cases. However, about half of patients have no response or loss of response to eltrombopag due to unknown reasons, which can't be effectively improved by increasing the drug dose. Diacerein is an anthraquinone derivative used to treat joint diseases such as osteoarthritis. We speculate that the addition of diacerein to eltrombopag may offer sensitizer effect and maximize efficacy, which warrants further prospective studies to evaluate the efficacy and safety of the combination therapy as salvage strategy in ameliorating immune thrombocytopenia.
详细描述
In this multicentre, open-label, randomized controlled trial, 98 eltrombopag-inefficient or relapsed ITP patients will be enrolled from five tertiary medical centres in China. Participants will be randomly assigned into the combination group (eltrombopag orally at initial dose of 75 mg daily for 14 days, plus diacerein orally at initial dose of 50 mg bid for 14 days) or the monotherapy group (eltrombopag orally at initial dose of 75 mg daily for 14 days) by masked statisticians in a 1:1 ratio. The primary endpoints are initial response at D15 without any additional ITP-specific intervention. The secondary outcomes include response at D28, time to response, duration of response, bleeding score, health-related quality of life assessment, and safety issue. This study will compare the efficacy and safety of eltrombopag-diacerein with eltrombopag monotherapy in adults with primary immune thrombocytopenia. We hypothesized that the novel combination of eltrombopag and diacerein might extend eltrombopag efficacy and avoid rapid alteration to less-preferable therapies, especially in the management of the patient refractory to eltrombopag.
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
- •Participant must be at least 18 years of age at the time of the screening.
- •Participant may be male or female.
- •Participant has a confirmed diagnosis of ITP according to the 2019 International Working Group assessment at screening.
- •Participant who didn't respond to eltrombopag retreatment (75mg by mouth once a day for 14 days) after eltrombopag previous treatment inefficient or relapsed (platelet count below 30 × 10^9/L or below 2-fold increase from baseline platelet count, or bleeding).
- •Bone marrow biopsy is performed in participants over 60 years to exclude hematological malignancies.
排除标准
- •Participant has evidence of a secondary cause of immune thrombocytopenia (e.g. leukemia, lymphoma, common variable immune-deficiency, systemic lupus erythematosus, autoimmune thyroid disease, past medical history of untreated H. pylori infection) or to drug treatments (e.g. heparin, quinine, antimicrobials, anticonvulsants) or participant has a multiple immune cytopenia, e.g. Evan's syndrome.
- •Participant has clinically life-threatening bleeding (e.g. central nervous system bleeding, menorrhagia with significant drop in hemoglobin). Participant has a history of coagulopathy disorders other than ITP.
- •Participant has a history of arterial or venous thromboembolism (e.g. stroke, transient ischemic attach, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the 6 months prior to randomization or requires anticoagulant treatment.
- •Participant has 12-lead ECG with changes considered to be clinically significant upon medical review at baseline.
- •Participant has severe renal impairment (glomerular filtration rate less than 45ml/min/1.73 m2).
- •Participant has 3 × upper limit of normal of any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase.
- •Participant has received corticosteroids, rh-TPO, romiplostim, or immunosuppression within 4 weeks before screening.
- •Participant with any of the following conditions: severe immunodeficiency, active or previous malignancy, human immunodeficiency virus (HIV), hepatitis B or C virus infection, pregnancy or lactation.
研究组 & 干预措施
Combination group
Eltrombopag plus diacerein
干预措施: Eltrombopag plus diacerein (Drug)
Monotherapy group
Eltrombopag monotherapy
干预措施: Eltrombopag (Drug)
结局指标
主要结局
Initial response at Day 15
时间窗: Day 15
The primary outcomes of this trial are initial responses at Day 15 without any additional ITP-specific intervention. Complete response was defined as a platelet count at or above 100 × 10⁹ cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 10⁹ cells per L but less than 100 × 10⁹ cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. No response was defined as a platelet count of less than 30 × 10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding.
次要结局
- Duration of response(12 months)
- Bleeding scores(12 months)
- Response at Day 28(Day 28)
- Time to response(28 days)
- Health-related quality of life assessment(12 weeks)
- The number of participants with Adverse events(12 months)