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

Primary Purpose

Lupus Nephritis

Status

Completed

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Tacrolimus+Mycophenolate mofetil

Cyclophosphamide

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring lupus nephritis;multi-target therapy; MMF; FK506

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent by subject or guardian
18 to 65 years of age (inclusive 18 and 65), male or female
Diagnosis of SLE according to the American College of Rheumatology criteria (1997)
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
Pathologic chronic index (CI) ≤3' without thrombotic microangiopathy (TMA)
SLE Disease Activity Index (DAI) >10'
Proteinuria ≥1.5g/d，with or without active urinary sediment
Serum creatinine (Scr)≤3.0mg/dl (265.2 mol/L)

Exclusion Criteria:

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
ALT or AST increase twice above the upper limit of the normal range
Hyperglycemia is defined as fasting blood glucose level ≥7.0 mmol/L and/or postprandial blood sugar level>11.1 mmol/L
Known hypersensitivity or contraindication to any components of MMF, tacrolimus, CTX or glucocorticoids
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
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
Severe infection or need of antibiotic therapy
Female patients who are pregnant/breastfeeding or those patients (both gender) who refused contraception
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
Known to be non-compliance or violation of the protocol base on investigator's judgement
Patient who participate of any other investigational drug study.

Sites / Locations

Research Institute of Nephrology,Jinling Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tacrolimus+Mycophenolate mofetil

Cyclophosphamide

Arm Description

FK506 4mg/d+MMF 1.0g/d

CTX iv 0.75 g/m2 body surface area (BSA)

Outcomes

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.

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.

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.

Full Information

NCT ID

NCT00876616

First Posted

April 6, 2009

Last Updated

August 28, 2013

Sponsor

Zhi-Hong Liu, M.D.

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00876616

Brief Title

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

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Zhi-Hong Liu, M.D.

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lupus Nephritis

Keywords

lupus nephritis;multi-target therapy; MMF; FK506

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

362 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tacrolimus+Mycophenolate mofetil

Arm Type

Experimental

Arm Description

FK506 4mg/d+MMF 1.0g/d

Arm Title

Cyclophosphamide

Arm Type

Active Comparator

Arm Description

CTX iv 0.75 g/m2 body surface area (BSA)

Intervention Type

Drug

Intervention Name(s)

Tacrolimus+Mycophenolate mofetil

Other Intervention Name(s)

FK506+MMF

Intervention Description

FK506 4mg/d,MMF 1.0g/d

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

CTX

Intervention Description

CTX 0.75g/m2 BSA

Primary Outcome Measure Information:

Title

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.

Description

The primary endpoint is the rate of complete remission at 24 weeks.

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

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.

Description

Time Frame

24 weeks

Other Pre-specified Outcome Measures:

Title

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.

Description

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.

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent by subject or guardian 18 to 65 years of age (inclusive 18 and 65), male or female Diagnosis of SLE according to the American College of Rheumatology criteria (1997) 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 Pathologic chronic index (CI) ≤3' without thrombotic microangiopathy (TMA) SLE Disease Activity Index (DAI) >10' Proteinuria ≥1.5g/d，with or without active urinary sediment Serum creatinine (Scr)≤3.0mg/dl (265.2 mol/L) Exclusion Criteria: 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 ALT or AST increase twice above the upper limit of the normal range Hyperglycemia is defined as fasting blood glucose level ≥7.0 mmol/L and/or postprandial blood sugar level>11.1 mmol/L Known hypersensitivity or contraindication to any components of MMF, tacrolimus, CTX or glucocorticoids History of present illness: 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 non-healed active peptic ulcer within 3 months before the enrollment drug or drinking abuse malnutrition (BMI <18.5kg/m2) or body weight <50Kg Other active diseases, such as: severe cardiovascular diseases chronic obstructive pulmonary disease(COPD)or asthma requiring oral glucocorticoids marrow depression not due to SLE activation: white blood cell count <3000/mm3 or neutrophil count <1300/mm3 or platelet count <50000/mm3 Severe infection or need of antibiotic therapy Female patients who are pregnant/breastfeeding or those patients (both gender) who refused contraception 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 Known to be non-compliance or violation of the protocol base on investigator's judgement Patient who participate of any other investigational drug study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhihong Liu, Master

Organizational Affiliation

Nanjing University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Institute of Nephrology,Jinling Hospital

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210002

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

25383558

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.

Results Reference

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

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