search
Back to results

Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study (CYCLOFA-LUNE)

Primary Purpose

Systemic Lupus Erythematosus, Lupus Nephritis

Status
Completed
Phase
Phase 2
Locations
Czech Republic
Study Type
Interventional
Intervention
Cyclosporine A
Cyclophosphamide
Sponsored by
Institute of Rheumatology, Prague
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring SLE, lupus nephritis, cyclosporine A, cyclophosphamide, active proliferative lupus nephritis (class III or IV according to WHO)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • the diagnosis of systemic lupus erythematosus (by meeting 4 criteria of the American College of Rheumatology)
  • renal biopsy documenting lupus nephritis according to the classification of the World Health Organization (WHO) or the updated International Society of Nephrology/Renal Pathology Society (ISN/RPS) as proliferative glomerulonephritis class III (focal) or IV (diffuse)

  • clinical activity as defined by presence of at least two of the following:

    • abnormal proteinuria (more than 500mg of protein in in a 24-hour urine specimen)
    • abnormal microscopic hematuria, or
    • C3 hypocomplementemia (the latter two were defined according to the norms in the laboratories of the participating centers)

Exclusion Criteria:

  • treatment with cyclophosphamide or cyclosporine A ever before
  • treatment with other immunosuppressive drugs (such as azathioprine or mycophenolate mofetil) or high dose glucocorticoids (≥ 80mg of prednisone or methylprednisolone) within the last 3 months
  • persistent elevation of serum creatinine (≥140 μmol/l)
  • pregnancy or lactation
  • bone marrow insufficiency with cytopenias not attributable to SLE, and 8severe coexisting conditions, such as infection, liver disease, active peptic ulcer etc.

Sites / Locations

  • Department of Rheumatology, Faculty of Medicine, Charles University in Prague
  • Department of Rheumatology, Faculty of Medicine, Palacky University
  • Department of Nephrology, General Teaching Hospital and First faculty of Medicine, Charles University in Prague
  • Institute of Rheumatology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cyclosporine A

Cyclophosphamide

Arm Description

Cyclosporine arm (CyA group) consisted of oral cyclosporine A (CyA) 4-5mg/kg/day (given in two divided doses) for 9 months followed by gradually decreasing dose of cyclosporine (3.75-1.25 mg/kg/day) within the next 9 months.

Cyclophosphamide (CPH) therapeutic arm (CPH group) consisted of 8 boluses of intravenous cyclophosphamide (10mg/kg) given within 9 months in subsequently prolonged intervals (2x3weeks, 4x4 weeks, 2x6 weeks) followed by 4-5 oral cyclophosphamide boluses (10mg/d in 6-8 week intervals).

Outcomes

Primary Outcome Measures

renal remission and renal response

Secondary Outcome Measures

incidence of adverse events and relapse free period

Full Information

First Posted
September 11, 2009
Last Updated
June 22, 2010
Sponsor
Institute of Rheumatology, Prague
Collaborators
Ministry of Health, Czech Republic, Charles University, Czech Republic, Palacky University, Department of Rheumatology, Hospital, Ceske Budejovice, Czech Republic, National Institute of Rheumatology, Piestany, Slovakia, St. Anna Hospital, Brno, Czech
search

1. Study Identification

Unique Protocol Identification Number
NCT00976300
Brief Title
Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study
Acronym
CYCLOFA-LUNE
Official Title
Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
January 2002 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Institute of Rheumatology, Prague
Collaborators
Ministry of Health, Czech Republic, Charles University, Czech Republic, Palacky University, Department of Rheumatology, Hospital, Ceske Budejovice, Czech Republic, National Institute of Rheumatology, Piestany, Slovakia, St. Anna Hospital, Brno, Czech

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Intravenous cyclophosphamide is considered to be the standard of care for treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. In a randomized, multicenter, open-label, controlled trial the investigators sought to compare the efficacy of oral cyclosporine A with intravenous pulse cyclophosphamide to induce durable remission in patients with lupus nephritis III-IV.
Detailed Description
Lupus nephritis occurs in 30-40% of adults with systemic lupus erythematosus and is associated with increased morbidity and mortality. Focal and diffuse proliferative forms of lupus nephritis are known to progress to chronic renal failure unless treated by immunosuppressive drugs. Cyclophosphamide and glucocorticoids are considered to be the standard of care for patients with proliferative lupus nephritis. However, cyclophosphamide may cause a number of toxic effects, such as bone marrow suppression, premature gonadal failure, hemorrhagic cystitis, opportunistic infections, and malignant disease. Hence, efforts are being made to find alternative therapeutic approaches. Cyclosporine is a potent immunosuppressive agent with a more selective mode of action through its unique effect on T cell mediated responses, and is widely used to treat a spectrum of autoimmune and glomerular diseases. Several retrospective series and one randomized trial provided evidence that Cyclosporine A could represent an efficient and safe therapy for proliferative lupus nephritis. In a randomized, multicenter, open-label, controlled trial we compared the efficacy of oral cyclosporine A with intravenous pulse cyclophosphamide to induce durable remission in patients with proliferative lupus nephritis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus, Lupus Nephritis
Keywords
SLE, lupus nephritis, cyclosporine A, cyclophosphamide, active proliferative lupus nephritis (class III or IV according to WHO)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cyclosporine A
Arm Type
Experimental
Arm Description
Cyclosporine arm (CyA group) consisted of oral cyclosporine A (CyA) 4-5mg/kg/day (given in two divided doses) for 9 months followed by gradually decreasing dose of cyclosporine (3.75-1.25 mg/kg/day) within the next 9 months.
Arm Title
Cyclophosphamide
Arm Type
Active Comparator
Arm Description
Cyclophosphamide (CPH) therapeutic arm (CPH group) consisted of 8 boluses of intravenous cyclophosphamide (10mg/kg) given within 9 months in subsequently prolonged intervals (2x3weeks, 4x4 weeks, 2x6 weeks) followed by 4-5 oral cyclophosphamide boluses (10mg/d in 6-8 week intervals).
Intervention Type
Drug
Intervention Name(s)
Cyclosporine A
Intervention Description
Cyclosporine arm (CyA group) consisted of oral cyclosporine A (CyA) 4-5mg/kg/day (given in two divided doses) for 9 months followed by gradually decreasing dose of cyclosporine (3.75-1.25 mg/kg/day) within the next 9 months. The dosage of concomitant glucocorticoids was driven and tapered according to a single treatment protocol.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide (CPH) therapeutic arm (CPH group) consisted of 8 boluses of intravenous cyclophosphamide (10mg/kg) given within 9 months in subsequently prolonged intervals (2x3weeks, 4x4 weeks, 2x6 weeks) followed by 4-5 oral cyclophosphamide boluses (10mg/d in 6-8 week intervals). The dosage of concomitant glucocorticoids was driven and tapered according to a single treatment protocol.
Primary Outcome Measure Information:
Title
renal remission and renal response
Time Frame
at the end of induction (month 9) and maintenance (month 18) phase
Secondary Outcome Measure Information:
Title
incidence of adverse events and relapse free period
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: the diagnosis of systemic lupus erythematosus (by meeting 4 criteria of the American College of Rheumatology) renal biopsy documenting lupus nephritis according to the classification of the World Health Organization (WHO) or the updated International Society of Nephrology/Renal Pathology Society (ISN/RPS) as proliferative glomerulonephritis class III (focal) or IV (diffuse) clinical activity as defined by presence of at least two of the following: abnormal proteinuria (more than 500mg of protein in in a 24-hour urine specimen) abnormal microscopic hematuria, or C3 hypocomplementemia (the latter two were defined according to the norms in the laboratories of the participating centers) Exclusion Criteria: treatment with cyclophosphamide or cyclosporine A ever before treatment with other immunosuppressive drugs (such as azathioprine or mycophenolate mofetil) or high dose glucocorticoids (≥ 80mg of prednisone or methylprednisolone) within the last 3 months persistent elevation of serum creatinine (≥140 μmol/l) pregnancy or lactation bone marrow insufficiency with cytopenias not attributable to SLE, and 8severe coexisting conditions, such as infection, liver disease, active peptic ulcer etc.
Facility Information:
Facility Name
Department of Rheumatology, Faculty of Medicine, Charles University in Prague
City
Hradec Kralove
Country
Czech Republic
Facility Name
Department of Rheumatology, Faculty of Medicine, Palacky University
City
Olomouc
Country
Czech Republic
Facility Name
Department of Nephrology, General Teaching Hospital and First faculty of Medicine, Charles University in Prague
City
Prague
ZIP/Postal Code
12800
Country
Czech Republic
Facility Name
Institute of Rheumatology
City
Prague
ZIP/Postal Code
12850
Country
Czech Republic

12. IPD Sharing Statement

Citations:
PubMed Identifier
17396037
Citation
Rihova Z, Vankova Z, Maixnerova D, Dostal C, Jancova E, Honsova E, Merta M, Rysava R, Tesar V. Treatment of lupus nephritis with cyclosporine - an outcome analysis. Kidney Blood Press Res. 2007;30(2):124-8. doi: 10.1159/000101448. Epub 2007 Mar 30.
Results Reference
background
PubMed Identifier
9493146
Citation
Dostal C, Tesar V, Rychlik I, Zabka J, Vencovsky J, Bartunkova J, Stejskalova A, Tegzova D. Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study. Lupus. 1998;7(1):29-36. doi: 10.1191/096120398678919714.
Results Reference
background
PubMed Identifier
15082482
Citation
Yee CS, Gordon C, Dostal C, Petera P, Dadoniene J, Griffiths B, Rozman B, Isenberg DA, Sturfelt G, Nived O, Turney JH, Venalis A, Adu D, Smolen JS, Emery P. EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis. Ann Rheum Dis. 2004 May;63(5):525-9. doi: 10.1136/ard.2002.003574.
Results Reference
background
PubMed Identifier
20605876
Citation
Zavada J, Pesickova S, Rysava R, Olejarova M, Horak P, Hrncir Z, Rychlik I, Havrda M, Vitova J, Lukac J, Rovensky J, Tegzova D, Bohmova J, Zadrazil J, Hana J, Dostal C, Tesar V. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study. Lupus. 2010 Oct;19(11):1281-9. doi: 10.1177/0961203310371155. Epub 2010 Jul 6.
Results Reference
derived

Learn more about this trial

Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study

We'll reach out to this number within 24 hrs