Overview
The goal of this clinical trial is to learn the efficacy and safety of sirolimus in the treatment of anti-phospholipid antibody associated thrombocytopenia. The patients would be followed at 2 weeks, 1 month, 3 months, and 6 months after the enrollment. The main questions it aims to answer are the differences between sirolimus and control group at below outcomes:
Primary outcome: the overall response rate at 6 months Secondary outcome: the complete response rate at 6 months the partial response rate at 6 months the change of anti-phospholipid antibody titers the change of oral glucocorticoids dosage Other pre-defined outcome: the dropout rate within 6 months Participants will receive either sirolimus 1mg per day or placebo.
Description
Complete response: the platelet count is more that 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
Eligibility
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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