Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory PNH
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|ClinicalTrials.gov Identifier: NCT03866681|
Recruitment Status : Not yet recruiting
First Posted : March 7, 2019
Last Update Posted : March 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Paroxysmal Nocturnal Hemoglobinuria||Drug: sirolimus||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study|
|Estimated Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||March 1, 2021|
|Estimated Study Completion Date :||April 1, 2022|
Experimental: 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
The dose of sirolimus is adjusted according to monitored serum concentration, maintain Rapamycin concentration ranging from 4 to 10ng/ml.Warfarin was administered orally at a dose of 1mg per day for a year,then gradually reduced to stop.
Other Name: warfarin
- Hemoglobin [ Time Frame: 2 years ]Hemoglobin in g/L
- Short Form 36 items(SF-36) questionnaire [ Time Frame: 2 years ]SF-36 questionnaire in scores
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866681
|Peking union medical college hospital|
|Contact: Bing Han, Doctor +86-010-69155760 email@example.com|