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

This study has been completed.
Sponsor:
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
Faculty Hospital St. Anna, Brno
Information provided by:
Institute of Rheumatology, Prague
ClinicalTrials.gov Identifier:
NCT00976300
First received: September 11, 2009
Last updated: June 22, 2010
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Systemic Lupus Erythematosus
Lupus Nephritis
Drug: Cyclosporine A
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study

Resource links provided by NLM:


Further study details as provided by Institute of Rheumatology, Prague:

Primary Outcome Measures:
  • renal remission and renal response [ Time Frame: at the end of induction (month 9) and maintenance (month 18) phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • incidence of adverse events and relapse free period [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: January 2002
Study Completion Date: April 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.
Active Comparator: 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).
Drug: 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.

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00976300

Locations
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
Institute of Rheumatology
Prague, Czech Republic, 12850
Department of Nephrology, General Teaching Hospital and First faculty of Medicine, Charles University in Prague
Prague, Czech Republic, 12800
Sponsors and Collaborators
Institute of Rheumatology, Prague
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
Faculty Hospital St. Anna, Brno
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Institute of Rheumatology, Prague
ClinicalTrials.gov Identifier: NCT00976300     History of Changes
Other Study ID Numbers: RU 8444-3, IGA MZ CR 8444-3, MZO 00023728
Study First Received: September 11, 2009
Last Updated: June 22, 2010
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by Institute of Rheumatology, Prague:
SLE
lupus nephritis
cyclosporine A
cyclophosphamide
active proliferative lupus nephritis (class III or IV according to WHO)

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Nephritis
Lupus Nephritis
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Cyclophosphamide
Cyclosporins
Cyclosporine
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
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 30, 2014