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

Phase 2

Completed

• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis
• Interventions: Drug: Cyclosporine A; Drug: Cyclophosphamide

• Registration Number: NCT00976300
• Lead Sponsor: Institute of Rheumatology, Prague

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.

Study Timeline

• Study Start: 2002-01
• Primary Completion: 2008-05
• Study Completion: 2009-04
• Status Verified: 2009-09
• Study First Submitted: 2009-09-11
• Study First Submitted QC: 2009-09-11
• Study First Posted: 2009-09-14
• Last Update Submitted: 2010-06-22
• Last Update Posted: 2010-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclosporine A	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.
Cyclophosphamide	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).

Primary Outcome Measures

Name	Time	Method
renal remission and renal response	at the end of induction (month 9) and maintenance (month 18) phase

Secondary Outcome Measures

Name	Time	Method
incidence of adverse events and relapse free period	18 months

Trial Locations

Locations (4)

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

Institute of Rheumatology; 🇨🇿 Prague, Czech Republic

Department of Nephrology, General Teaching Hospital and First faculty of Medicine, Charles University in Prague; 🇨🇿 Prague, Czech Republic