Using sirolimus to treat thrombocytopenia related to antiphospholipid antibodies

Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia: a Multicenter Randomized, Double Blind, Placebo Controlled, Clinical Trial

This study is testing if the medication sirolimus can help people with low platelet counts caused by antiphospholipid antibodies feel better compared to those who receive a placebo.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University First Hospital (Academic / other)
• Drugs / interventions: Belimumab, Rituximab, Obinutuzumab, prednisone
• Locations: 10 sites (Changsha, Hunan and 9 other locations)
• Trial ID: NCT06722586 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of sirolimus in patients with antiphospholipid antibody-related thrombocytopenia. Participants will be randomly assigned to receive either sirolimus or a placebo, with follow-up assessments at 2 weeks, 1 month, 3 months, and 6 months. The primary outcome is the overall response rate at 6 months, while secondary outcomes include complete and partial response rates and changes in antiphospholipid antibody titers. The study will help determine the effectiveness of sirolimus compared to a control group.

Who should consider this trial

Good fit: Ideal candidates include individuals with persistent antiphospholipid antibodies and thrombocytopenia who meet specific inclusion criteria.

Not a fit: Patients with other connective tissue diseases or those who have recently received certain immunosuppressive therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from thrombocytopenia associated with antiphospholipid syndrome.

How similar studies have performed: While the use of sirolimus in this context is novel, similar studies have shown promise in treating related conditions with immunomodulatory therapies.

Eligibility criteria

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

Where this trial is running

Changsha, Hunan and 9 other locations

• Xiangya Hospital of Central South University — Changsha, Hunan, China (Recruiting)
• Qilu Hospital of Shandong University — Jinan, Shangdong, China (Recruiting)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)
• People's Hospital of Xinjiang Uygur Autonomous Region — Ürümqi, Xinjiang, China (Recruiting)
• The 1st Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)
• Beijing Chao-Yang Hospital — Beijing, China (Recruiting)
• Peking University First Hospital — Beijing, China (Recruiting)
• Peking University Third Hospital — Beijing, China (Recruiting)
• Beijing Shijitan Hospital — Beijing, China (Recruiting)
• Shanghai Renji Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Lanlan Ji

Conditions Antiphospholipid-Positive; Thrombocytopaenia; antiphospholipid; thrombocytopaenia; sirolimus; rapamycin