Tacrolimus Versus Cyclophosphamide as Treatment for Lupus Nephritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jianghua Chen, Zhejiang University
ClinicalTrials.gov Identifier:
NCT01207297
First received: September 21, 2010
Last updated: August 22, 2011
Last verified: September 2010
  Purpose

In this comparative open-label cohort study, the investigators compared the efficacy and safety of tacrolimus (TAC)and cyclophosphamide (CYC) in the treatment of diffuse proliferative and membranous lupus nephritis with severe renal disease. Treatment of lupus nephritis (LN) with cyclophosphamide is effective, but retain a certain proportion of renal function exacerbations. Tacrolimus may be a suitable substitute treatment for CYC.

Methods: Forty patients with diffuse proliferative or membranous were recruited for this trial, 45% of them had lower Ccr (<60mL/min/1.73m2), 10% had increased serum creatinine (>180µmol/L) and 67.5% had nephritic proteinuria (>3.5g/day). The investigators compared the efficacy and adverse effects of TAC (0.04-0.08 mg/kg/d) and prednisone for 12 months (TAC group) with pulse cyclophosphamide (750mg/m2 per month for six months) and prednisone followed by azathioprine (50mg/day)for 6 months (CYC group).


Condition Intervention Phase
SLE
Lupus Nephritis
Renal Insufficiency
End-stage Renal Disease
Drug: Tacrolimus
Drug: cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tacrolimus Versus Cyclophosphamide as Treatment for Diffuse Proliferative or Membranous Lupus Nephritis: Prospective Cohort Study

Resource links provided by NLM:


Further study details as provided by Zhejiang University:

Primary Outcome Measures:
  • Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    The primary study outcome measure was the cumulative rate of complete remission (CR).


Secondary Outcome Measures:
  • Evaluating the effective and safety of TAC for severe lupus nephritis compared CYC protocol. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    The secondary outcome measure were time required for CR, cumulative rate of sustained remission, relapse rate, immunological parameters, side effects, renal function during treatment and followed-up, and compliance with therapy and TAC dosing and serum levels.


Enrollment: 40
Study Start Date: March 2003
Study Completion Date: June 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: TAC group
Oral tacrolimus (0.04-0.08 mg/kg/d) and prednisone for 12 months.
Drug: Tacrolimus

The calcineurin inhibitor is widely administered for organ transplantation,which establish the current method for lupus nephritis (LN).

20 patients with LN were self-assigned the therapy of TAC and prednisone for 12 months. The dosage was adjusted to achieve a whole blood TAC 12 h trough concentration.

Other Name: Prograf
Active Comparator: CYC group
Pulse cyclophosphamide (750mg/m2 per month for six months) and prednisone followed by azathioprine (50mg/day)for 6 months.
Drug: cyclophosphamide
20 patients with LN were self-assigned the protolcol of intravenous cyclophosphamide (750mg/m2 per month)/prednisone for six months followed by azathioprine(100mg/day)/prednisone for six months.
Other Name: Cyclophosphamide

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • SLE patients:diagnosis based on American Rheumatism Association criteria;
  • renal biopsy-proven active LN (diffuse proliferative and membranous lupus nephritis, class IV, V, V+IV and/or V+III, according to the ISN/RPS 2003 classification13)
  • urinary protein excretion of at least 2.0 g per 24 h
  • serum creatinine less than 221 µmol/dL (2.5mg/dL)
  • creatinine clearance more than 30 mL/min/1.73m2

Exclusion Criteria:

  • pregnant or lactating
  • previous treatment with cyclosporine, mycophenolate mofetil treatment for at least two weeks in the previous three months
  • known allergies to calcineurin inhibitors
  • severe infection or illness
  • symptoms of a central nervous system disorder
  • alanine aminotransferase more than 100U/L
  • evidence of active hepatitis
  • fasting blood glucose more than 6.2 mmol/L
  • 2 h post-meal blood glucose more than 11.1mmol/L
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01207297

Sponsors and Collaborators
Zhejiang University
Investigators
Principal Investigator: Jianghua Chen, MD The First Affiliated Hospital, College of Medicine, Zhejiang University
  More Information

No publications provided

Responsible Party: Jianghua Chen, Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis: prospective cohort study, Zhejiang University
ClinicalTrials.gov Identifier: NCT01207297     History of Changes
Other Study ID Numbers: ChiCTR-TKMS-1000960, ChiCTR-TNRC-10000960
Study First Received: September 21, 2010
Last Updated: August 22, 2011
Health Authority: China:Chineses Clinical Trial Register

Keywords provided by Zhejiang University:
Lupus nephritis
tacrolimus
cyclophosphamide

Additional relevant MeSH terms:
Lupus Nephritis
Lupus Erythematosus, Systemic
Kidney Diseases
Kidney Failure, Chronic
Nephritis
Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
Glomerulonephritis
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Tacrolimus
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

ClinicalTrials.gov processed this record on August 28, 2014