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

This study has been completed.
Sponsor:
Collaborators:
Ruijin Hospital
West China Hospital
RenJi Hospital
China Medical University, China
Huashan Hospital
Jiangsu Province Hospital
Beijing Friendship Hospital
Shanghai First People's Hospital
Information provided by (Responsible Party):
Zhi-Hong Liu, M.D., Nanjing University School of Medicine
ClinicalTrials.gov Identifier:
NCT00876616
First received: April 6, 2009
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention
Lupus Nephritis
Drug: Tacrolimus+Mycophenolate mofetil
Drug: Cyclophosphamide

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

Resource links provided by NLM:


Further study details as provided by Nanjing University School of Medicine:

Primary Outcome Measures:
  • 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. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    The primary endpoint is the rate of complete remission at 24 weeks.


Secondary Outcome Measures:
  • 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. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • 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. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 362
Study Start Date: April 2009
Study Completion Date: February 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tacrolimus+Mycophenolate mofetil
FK506 4mg/d+MMF 1.0g/d
Drug: Tacrolimus+Mycophenolate mofetil
FK506 4mg/d,MMF 1.0g/d
Other Name: FK506+MMF
Active Comparator: Cyclophosphamide
CTX iv 0.75 g/m2 body surface area (BSA)
Drug: Cyclophosphamide
CTX 0.75g/m2 BSA
Other Name: CTX

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00876616

Locations
China, Jiangsu
Research Institute of Nephrology,Jinling Hospital
Nanjing, Jiangsu, China, 210002
Sponsors and Collaborators
Zhi-Hong Liu, M.D.
Ruijin Hospital
West China Hospital
RenJi Hospital
China Medical University, China
Huashan Hospital
Jiangsu Province Hospital
Beijing Friendship Hospital
Shanghai First People's Hospital
Investigators
Principal Investigator: Zhihong Liu, Master Nanjing University School of Medicine
  More Information

No publications provided

Responsible Party: Zhi-Hong Liu, M.D., professor, Nanjing University School of Medicine
ClinicalTrials.gov Identifier: NCT00876616     History of Changes
Other Study ID Numbers: NJCT-0901
Study First Received: April 6, 2009
Last Updated: August 28, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Nanjing University School of Medicine:
lupus nephritis;multi-target therapy; MMF; FK506

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Mycophenolate mofetil
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014