Lupus Nephritis
Conditions
Keywords
lupus nephritis;multi-target therapy; MMF; FK506
Brief summary
The purpose of this study is to assess the efficacy and safety of multi-target therapy in the treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ lupus nephritis.
Detailed description
1. To assess the efficacy of FK506 combined with MMF vs intravenous cyclophosphamide (CTX) pulses in treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ Lupus Nephritis (LN). 2. To investigate the safety and tolerability of FK506 combined with MMF vs intravenous CTX pulses in the treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ LN.
Interventions
DRUGTacrolimus+Mycophenolate mofetil
FK506 4mg/d,MMF 1.0g/d
DRUGCyclophosphamide
CTX 0.75g/m2 BSA
Sponsors
Ruijin Hospital
West China Hospital
RenJi Hospital
China Medical University, China
Huashan Hospital
The First Affiliated Hospital with Nanjing Medical University
Beijing Friendship Hospital
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Zhi-Hong Liu, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent by subject or guardian 2. 18 to 65 years of age (inclusive 18 and 65), male or female 3. Diagnosis of SLE according to the American College of Rheumatology criteria (1997) 4. Diagnosis of Class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+ⅤLN according to the ISN/RPS 2003 classification by light, immunofluorescence, and electron microscopy within 6 months before enrollment 5. Pathologic chronic index (CI) ≤3' without thrombotic microangiopathy (TMA) 6. SLE Disease Activity Index (DAI) \>10' 7. Proteinuria ≥1.5g/d，with or without active urinary sediment 8. Serum creatinine (Scr)≤3.0mg/dl (265.2 mol/L)
Exclusion criteria
1. Previous treatment with MMF, CTX, tacrolimus, Cyclosporin A (CsA), large doses of immunoglobulin and methylprednisolone (MP), plasmapheresis or renal replacement therapy within the past 12 weeks. Oral glucocorticoids, azathioprine, intravenous MP (≤80mg/d)， short-time CsA (\<2 weeks) or leflunomide (\<4 weeks) are allowed 2. ALT or AST increase twice above the upper limit of the normal range 3. Hyperglycemia is defined as fasting blood glucose level ≥7.0 mmol/L and/or postprandial blood sugar level\>11.1 mmol/L 4. Known hypersensitivity or contraindication to any components of MMF, tacrolimus, CTX or glucocorticoids 5. History of present illness: 1. active HBV infection (HBsAg, HBeAg and anti-HBc positive or HBsAg, anti- HBe and anti-HBc positive), HCV infection, pulmonary tuberculosis, cytomegalovirus(CMV) infection (defined as CMV-IgM positive or CMV-DNA positive), fungal infection or HIV infection, within 3 months before the enrollment 2. non-healed active peptic ulcer within 3 months before the enrollment 3. drug or drinking abuse 4. malnutrition (BMI \<18.5kg/m2) or body weight \<50Kg 6. Other active diseases, such as: 1. severe cardiovascular diseases 2. chronic obstructive pulmonary disease(COPD)or asthma requiring oral glucocorticoids 3. marrow depression not due to SLE activation: white blood cell count \<3000/mm3 or neutrophil count \<1300/mm3 or platelet count \<50000/mm3 7. Severe infection or need of antibiotic therapy 8. Female patients who are pregnant/breastfeeding or those patients (both gender) who refused contraception 9. Life-threatening complications such as large hydropericardium, pneumohemorrhagia, lupus encephalopathy and severe pulmonary hypertension or patients in need of MP pulse (\>0.5g/d ) treatment because of aggravation of SLE 10. Known to be non-compliance or violation of the protocol base on investigator's judgement 11. Patient who participate of any other investigational drug study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of FK506 combined with MMF vs intravenous CTX pulses in treatment of class Ⅲ, Ⅳ,Ⅴ, Ⅲ+Ⅴand Ⅳ+Ⅴ LN. | 24 weeks | The primary endpoint is the rate of complete remission at 24 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the other efficacy indicators of FK506 combined with MMF vs intravenous CTX pulses in the treatment of class Ⅲ, Ⅳ,Ⅴ, Ⅲ+Ⅴand Ⅳ+Ⅴ LN. | 24 weeks | The secondary endpoints include total remission, time to complete remission and remission, rate of complete remission and remission in patients with different types of LN, changes between baseline and after 24 week of induction treatment in proteinuria, albumin, SCr, eGFR, complement, autoantibodies, SLE-DAI and dosage and concentration of immunosuppressants between groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To assess the Safety of FK506 combined with MMF vs intravenous CTX pulses in treatment of class Ⅲ, Ⅳ,Ⅴ, Ⅲ+Ⅴand Ⅳ+Ⅴ LN. | 24 weeks | Safety assessments include clinical manifestations, physical examination, laboratory tests laboratory tests (including hematology, serum chemistry, urinalysis), adverse events (including gastrointestinal toxicity and severe infections requiring antibiotics treatment) and concomitant medications. |
Countries
China
Outcome results
None listed