Assess the Efficacy and Safety of Multi-target Therapy in Lupus Nephritis

Lupus Nephritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00876616
• Other study ID #: NJCT-0901
• Status: Completed
• Phase: N/A
• First received: April 6, 2009
• Last updated: August 28, 2013
• Start date: April 2009
• Est. completion date: February 2012

Study information

• Verified date: August 2013
• Source: Nanjing University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 362
• Est. completion date: February 2012
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 ?,?,?,?+?and ?+?LN 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Tacrolimus+Mycophenolate mofetil
FK506 4mg/d,MMF 1.0g/d
• Cyclophosphamide
CTX 0.75g/m2 BSA

Locations

Country	Name	City	State
China	Research Institute of Nephrology,Jinling Hospital	Nanjing	Jiangsu

Sponsors (9)

Lead Sponsor	Collaborator
Zhi-Hong Liu, M.D.	Beijing Friendship Hospital, China Medical University, China, Huashan Hospital, RenJi Hospital, Ruijin Hospital, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, The First Affiliated Hospital with Nanjing Medical University, West China Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess the Safety of FK506 combined with MMF vs intravenous CTX pulses in treatment of class ?, ?,?, ?+?and ?+? LN.	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.	24 weeks	Yes
Primary	To assess the efficacy of FK506 combined with MMF vs intravenous CTX pulses in treatment of class ?, ?,?, ?+?and ?+? LN.	The primary endpoint is the rate of complete remission at 24 weeks.	24 weeks	Yes
Secondary	To investigate the other efficacy indicators of FK506 combined with MMF vs intravenous CTX pulses in the treatment of class ?, ?,?, ?+?and ?+? LN.	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.	24 weeks	Yes