Cyclosporine A or Intravenous Cyclophosphamide for Lupus Nephritis: The Cyclofa-Lune Study (CYCLOFA-LUNE)
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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 |
- renal remission and renal response [ Time Frame: at the end of induction (month 9) and maintenance (month 18) phase ] [ Designated as safety issue: No ]
- 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.
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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.
|
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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 |
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| 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 | |
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 Lupus Nephritis Nephritis Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Glomerulonephritis Kidney Diseases Urologic Diseases 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 May 16, 2013