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

Systemic Lupus Erythematosus Clinical Trial

— CYCLOFA-LUNE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976300
• Other study ID #: RU 8444-3
• Secondary ID: IGA MZ CR 8444-3
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2009
• Last updated: June 22, 2010
• Start date: January 2002
• Est. completion date: April 2009

Study information

• Verified date: September 2009
• Source: Institute of Rheumatology, Prague
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Lupus Nephritis
• Nephritis
• Systemic Lupus Erythematosus

Intervention

Drug:
• Cyclosporine A
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.
• Cyclophosphamide
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.

Locations

Country	Name	City	State
Czech Republic	Department of Rheumatology, Faculty of Medicine, Charles University in Prague	Hradec Kralove
Czech Republic	Department of Rheumatology, Faculty of Medicine, Palacky University	Olomouc
Czech Republic	Department of Nephrology, General Teaching Hospital and First faculty of Medicine, Charles University in Prague	Prague
Czech Republic	Institute of Rheumatology	Prague

Sponsors (7)

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

Country where clinical trial is conducted

Czech Republic, 

References & Publications (3)

Dostál C, Tesar V, Rychlík I, Zabka J, Vencovský J, Bartûnková J, Stejskalová 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. — View 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. Epub 2007 Mar 30. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	renal remission and renal response		at the end of induction (month 9) and maintenance (month 18) phase	No
Secondary	incidence of adverse events and relapse free period		18 months	Yes