Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia (SMART)

Peking University

Status and phase: Enrolling; Phase 4

Conditions: Antiphospholipid (aPL)-Positive; Thrombocytopaenia

Treatments: Drug: Placebo; Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT06722586

SMART_V2.1

Details and patient eligibility

About

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 Participants will receive either sirolimus 1mg per day or placebo.

Full 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

Enrollment: 84 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)
• prednisone or equivalent dose less than 10mg per day, and dose stable for more than 2 weeks
• hydroxychloroquine less than 400mg per day, and dose stable for more than 1 month
• strength of anti-platelet and/or anti-coagulant therapy is stable for 1 week

Exclusion criteria

• fulling the criteria of other connective tissue disease other than antiphospholipid syndrome
• received thrombopoietin or thrombopoietin receptor antagonist within 2 weeks before the enrollment; intravenous immunoglobulin within 1 month before the enrollment; immunosuppressants within 3 months before the enrollment; B cell inhibitors (Belimumab or Talitacicept) within 3 months before the enrollment; B cell depletion therapy (Rituximab) within 6 months before the enrollment.
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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84 participants in 2 patient groups, including a placebo group

Treatment

Experimental group

Description:

Sirolimus two pills (1mg) per day

Treatment:

Drug: Sirolimus

Control

Placebo Comparator group

Description:

Placebo two pills per day

Treatment:

Drug: Placebo