Clinical trial NCT00976300: Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study
Official title: Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lupus Nephritis
Keywords: SLE
lupus nephritis
cyclosporine A
cyclophosphamide
active proliferative lupus nephritis (class III or IV according to WHO)
Lead sponsor: Institute of Rheumatology, Prague
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Czech Republic
name: Charles University, Czech Republic
name: Palacky University
name: Department of Rheumatology, Hospital, Ceske Budejovice, Czech Republic
name: National Institute of Rheumatology, Piestany, Slovakia
name: St. Anna Hospital, Brno, Czech
First posted: 2009-09-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: renal remission and renal response
timeFrame: at the end of induction (month 9) and maintenance (month 18) phase
Secondary outcomes:
measure: incidence of adverse events and relapse free period
timeFrame: 18 months
Other outcomes:
Locations:
city: Hradec Kralove
country: Czech Republic
facility: Department of Rheumatology, Faculty of Medicine, Charles University in Prague
city: Olomouc
country: Czech Republic
facility: Department of Rheumatology, Faculty of Medicine, Palacky University
city: Prague
country: Czech Republic
facility: Department of Nephrology, General Teaching Hospital and First faculty of Medicine, Charles University in Prague
city: Prague
country: Czech Republic
facility: Institute of Rheumatology
Study officials:
References:
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.
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.
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.
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.