Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study
试验速览
- 阶段
- 4 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Hemoglobin
研究概览
简要总结
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. Glucocorticoids and symptomatic supportive therapy are traditional treatments and the response rate is far from satisfactory. Eculizumab is an effective therapy but it is expensive and not available in China mainland.The investigators aim to explore the efficacy and safety of sirolimus for refractory classic PNH.
详细描述
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. There is no ideal therapy except for eculizumab, expensive and not available in China mainland. Glucocorticoids and symptomatic supportive therapy are traditional treatments. The response rate is 30%, far from satisfactory. In recent years, T lymphocyte-mediated destruction of normal hematopoietic stem cells have been reported to involve the pathogenesis of PNH, making immunomodulatory drugs be potential effective treatments.
Sirolimus (rapamycin), produced by the bacterium Streptomyces hygroscopicus, is a mammalian target of Rapamycin (mTOR) inhibitor. mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival. It has two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been demonstrated for its immunomodulatory effects and ability to improve hematopoietic stem cell function. Recently, sirolimus has been reported to be effective and well tolerated in the treatment of immune-mediated cytopenias, even in multi-immunosuppressants resistant patients. In addition, classical PNH patients have a higher risk of thrombosis especially in refractory ones and it is reasonable to use low-dose warfarin in the management of patients with classic refractory PNH.
In this study, it is anticipated to evaluate the effect of sirolimus combined with low-dose warfarin on patients with refractory classic PNH. The adverse effects and QoL on different time points were documented.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 18-70 years
- •diagnosed with PNH and no thrombosis
- •ineffective, relapsed or intolerant to conventional treatment (eg glucocorticoids, • • iron, folic acid, androgen, etc.)
- •not available for hematopoietic stem cell transplantation
- •agreed to sign the consent forms
排除标准
- •severe heart, liver and kidney dysfunction
- •combined with thrombotic complications
- •people who are pregnant and breastfeeding
- •history of other immunosuppressive agents in recent 3 months
- •Patients who are not eligible to participate in this trial due to any reason based • • • on the consideration of investigator
研究组 & 干预措施
Patients cohort
A total of 40 patients with refractory classic PNH will be included and will be intervened by a combined therapy including sirolimus and low-dose warfarin
干预措施: sirolimus (Drug)
结局指标
主要结局
Hemoglobin
时间窗: 2 years
Hemoglobin in g/L
次要结局
- Short Form 36 items(SF-36) questionnaire(2 years)
研究者
Bing Han
Clinical Professor
Peking Union Medical College Hospital