Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia: a Multicenter Randomized, Double Blind, Placebo Controlled, Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 11
- 主要终点
- Overall response
研究概览
简要总结
The goal of this clinical trial is to evaluate the efficacy and safety of sirolimus in patients with anti-phospholipid antibody-associated thrombocytopenia.
In the 6-month randomized, double-blind, placebo-controlled phase, participants will receive either sirolimus 1 mg once daily or matching placebo. Participants will be followed at 2 weeks, 1 month, 3 months, and 6 months after enrollment.
Participants who do not achieve the primary endpoint at 6 months may enter a 3-month open-label extension and receive sirolimus 1.5 mg once daily, with follow-up through month 9.
The main question is whether sirolimus improves the overall response rate at 6 months compared with placebo.
Primary outcome:
- Overall response rate at 6 months
Secondary outcomes:
- Overall response rate at 1 month and 3 months
- Complete response rate at 6 months
- Partial response rate at 6 months
- Change in anti-phospholipid antibody titers at 6 months
- Change in oral glucocorticoid dosage at 6 months
Exploratory outcomes:
- Proportion and reasons for early discontinuation during the double-blind phase
- Among participants who do not achieve the primary endpoint at 6 months and enter the open-label extension, overall response rate, complete response rate, partial response rate, and safety outcomes after 3 months of open-label treatment
详细描述
Complete response: the platelet count is more than or equal to 100×10^9/L Partial response: If the platelet count is less than 100×10^9/L, it should be more than 2 times of the baseline count Overall response: both complete and partial response
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •persistent positive of antiphospholipid antibody (either lupus anticoagulant, anti-cardiolipin antibody, or anti-b2GP1 antibody, at least two times with 12 weeks apart)
- •persistent thrombocytopenia (30-100×10^9/L, at least for 2 weeks)
- •Eligible concomitant treatment:
- •prednisone or equivalent dose less than 10mg per day is allowed, and dose should be stable for more than 2 weeks
- •hydroxychloroquine less than 400mg per day is allowed, and dose should be stable for more than 1 month
- •anti-platelet and/or anti-coagulant therapy is allowed, and strength should be the stable for 1 week
- •these following therapies should be discontinued for more than 5 half-lives before the enrollment, including thrombopoietin or thrombopoietin receptor antagonist, intravenous immunoglobulin, immunosuppressants, B cell inhibitors (Belimumab or Talitacicept) and B cell depletion therapy (Rituximab or Obinutuzumab).
排除标准
- •fulling the criteria of other connective tissue disease other than antiphospholipid syndrome
- •received oral/intravenous antibiotics within 2 weeks before the enrollment.
- •new onset of thrombosis within 4 weeks before the enrollment.
- •apparent bleeding tendency.
- •life or organ threatening manifestations, includes but not limit to catastrophic antiphospholipid syndrome and thrombotic microangiopathy.
- •liver and renal dysfunction: ALT or AST more than three times of upper limit of normal range; eGFR<40mL/min/1.73m^2
- •hematocytopenia: WBC<3.0×10^9/L, Hb<100g/L.
- •uncontrollable hyperlipidemia: low density lipoprotein cholesterol>3.1 mmol/L, triglycerides>2.3 mmol/L after lipid lowering therapy.
- •current active infection
- •women in pregnancy and postpartum period
研究组 & 干预措施
Treatment
Participants receive sirolimus 1 mg (two pills) once daily for 6 months during the randomized, double-blind phase. Participants who do not achieve the primary endpoint at Month 6 may enter a 3-month open-label extension and receive sirolimus 1.5 mg once daily.
干预措施: Sirolimus (Drug)
Control
Participants receive matching placebo (two pills) once daily for 6 months during the randomized, double-blind phase. Participants who do not achieve the primary endpoint at Month 6 may enter a 3-month open-label extension and receive sirolimus 1.5 mg once daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Overall response
时间窗: From enrollment to the end of treatment at 6 months
Both complete response and partial response
Percentage of participants with overall response at Month 6
时间窗: Month 6
Overall response is defined as achieving either complete response or partial response. Complete response is defined as platelet count \>=100 x 10\^9/L. Partial response is defined as platelet count \<100 x 10\^9/L with at least a 2-fold increase from baseline. Participants with missing Month 6 assessment or meeting prespecified treatment failure criteria will be counted as non-responders.
次要结局
- Complete response(From enrollment to the end of treatment at 6 months)
- Partial response(From enrollment to the end of treatment at 6 months)
- The change of antiphospholipid antibodies titers(From enrollment to the end of treatment at 6 months)
- The change of oral glucocorticoids dosage(From enrollment to the end of treatment at 6 months)
- Percentage of participants with overall response at Month 1(Month 1)
- Percentage of participants with overall response at Month 3(Month 3)
- Percentage of participants with complete response at Month 6(Month 6)
- Percentage of participants with partial response at Month 6(Month 6)
- Change from baseline in Global Antiphospholipid Syndrome Score (GAPSS) at Month 6(Baseline and Month 6)
- Change from baseline in oral glucocorticoid dose at Month 6(Baseline and Month 6)
研究者
Zhuoli ZHANG
MD, PhD, Director of Rheumatology and Immunology Department
Peking University First Hospital