Clinical trial NCT00876616: Assess the Efficacy and Safety of Multi-target Therapy in Lupus Nephritis
Official title: An Multi-site, Open, Prospective Study to Assess the Efficacy and Safety of Multi-target Therapy in the Treatment of Class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lupus Nephritis
Keywords: lupus nephritis;multi-target therapy; MMF; FK506
Lead sponsor: Nanjing University School of Medicine
Sponsor class: OTHER
Collaborators: name: Ruijin Hospital
name: West China Hospital
name: RenJi Hospital
name: China Medical University, China
name: Huashan Hospital
name: The First Affiliated Hospital with Nanjing Medical University
name: Beijing Friendship Hospital
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
First posted: 2009-04-07
Enrollment: 362
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 24 weeks
Secondary outcomes:
measure: 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.
timeFrame: 24 weeks
Other outcomes:
measure: 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.
timeFrame: 24 weeks
Locations:
city: Nanjing
country: China
facility: Research Institute of Nephrology,Jinling Hospital
state: Jiangsu
Study officials:
affiliation: Nanjing University School of Medicine
name: Zhihong Liu, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu Z, Zhang H, Liu Z, Xing C, Fu P, Ni Z, Chen J, Lin H, Liu F, He Y, He Y, Miao L, Chen N, Li Y, Gu Y, Shi W, Hu W, Liu Z, Bao H, Zeng C, Zhou M. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med. 2015 Jan 6;162(1):18-26. doi: 10.7326/M14-1030.