Sirolimus in Patients With Systemic Lupus Erythematosus-Associated Immune Thrombocytopenia

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial and Open-Label Extension Study of Sirolimus in Patients With Systemic Lupus Erythematosus-Associated Immune Thrombocytopenia

The goal of this clinical trial is to learn if sirolimus, added to standard background therapy (corticosteroids and hydroxychloroquine), works to treat systemic lupus erythematosus-associated immune thrombocytopenia (SLE-ITP) in adults aged 18 to 65 years. The study also aims to evaluate the long-term effectiveness and safety of sirolimus over 48 weeks.

The main questions it aims to answer are:

1. Does sirolimus increase the overall response rate (complete or partial remission of thrombocytopenia) at 24 weeks compared with placebo?
2. The safety issues when taking sirolimus over 24 weeks (Phase 1) and up to 48 weeks (Phase 2).
3. How long does the treatment effect last, and what is the relapse rate during open-label extension? In Phase 1 (first 24 weeks), researchers will compare sirolimus to a placebo (an identical-looking capsule containing no active drug) to see if sirolimus works to treat SLE-ITP when both groups also receive standardized prednisone and hydroxychloroquine. In Phase 2 (weeks 24 to 48), all participants will receive open-label sirolimus to assess long-term efficacy and safety.

Participants will:

1. Phase 1: Take sirolimus (1.5 mg once daily) or a placebo for 24 weeks, plus standardized prednisone (tapered according to protocol) and hydroxychloroquine (0.4 g daily)
2. Phase 2: After completing Phase 1, take open-label sirolimus (1.5 mg once daily) for an additional 24 weeks, continuing stable or tapering doses of prednisone and hydroxychloroquine
3. Visit the clinic at screening, baseline, weeks 4, 12, 24 (end of Phase 1), and then at weeks 28, 36, and 48 (end of Phase 2) for checkups, blood tests, and disease activity assessments
4. Receive telephone follow-ups at weeks 8, 16, 20, 32, 40, and 44 to report platelet counts, medication adherence, and adverse events

Inclusion Criteria:

Age ≥ 18 and < 65 years

1. Meet 2012 SLICC or 2019 EULAR/ACR criteria for systemic lupus erythematosus
2. Meet ITP diagnostic criteria: platelet count ≤ 30×10^9/L, or ≤ 50×10^9/L with bleeding tendency
3. At least two CBC tests showing thrombocytopenia
4. Bone marrow smear showing megakaryocyte maturation disorder
5. Willing to sign informed consent form

Exclusion Criteria:

1. Other causes of thrombocytopenia
2. Refractory SLE-ITP (no partial response after 3 months of high-dose steroids or immunosuppressants)
3. Use of rituximab within 6 months
4. Severe organ involvement (e.g., proteinuria > 1g/24h, CNS involvement, cardiac/GI involvement)
5. Other autoimmune diseases (except Sjögren's syndrome)
6. Malignancy
7. Active infections (HIV, HBV, HCV, syphilis)
8. Severe liver or kidney dysfunction
9. Splenomegaly
10. Pregnancy or breastfeeding
11. Contraindications to study drugs
12. Unhealed major wounds or incisions
13. Judged unsuitable by investigator