Drug Therapy in Lupus Nephropathy

Launched by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES (NIDDK) · Nov 3, 1999

Keywords

ClinConnect Summary

This is a phase 2 trial to evaluate the effectiveness and toxicity of immunosuppressive drug therapy in patients with membranous lupus nephropathy over a 12 month study period. Patients with renal biopsy documented membranous nephropathy will all be treated with alternate day prednisone and will be randomized to receive: a) no additional therapy (control group), b) intravenous cyclophosphamide up to 1.0 gm per m(2) body surface area every other month for 6 total doses, or c) oral cyclosporin A up to 200 mg per m(2) body surface area daily for a total of 11 months. Patients with glomerular f...

Gender

ALL

Eligibility criteria

• INCLUSION CRITERIA - All patients admitted to the study must satisfy each of the following criteria:
• • Ability to provide informed consent to all aspects of the study after full information is provided.
• • SLE as defined by the presence of at least 4 criteria established by the American Rheumatism Association.
• • Age 12 years or older.
• • Membranous lupus nephropathy manifested by 2 or more grams per day of proteinuria in the absence of infection or recognized non-lupus renal disease. A renal biopsy must reveal typical membranous lupus nephropathy by light microscopy. Immune deposits must be predominately sub-epithelial and/or intramembranous in location by electron microscopy.
• EXCLUSION CRITERIA - Patients with any one of the following conditions will be excluded:
• Medication history of:
• • cytotoxic drugs or cyclosporin A for more than 2 weeks during the 10 week period prior to study entry.
• • cytotoxic drug therapy or cyclosporin A for more than 10 weeks at anytime in the past.
• • cytotoxic drug therapy or cyclosporin A during the 30 day period prior to study entry.
• • requirement of corticosteroids in doses greater than 20 mg/m(2)/day of prednisone (or equivalent) for control of extrarenal disease at the time of study entry.
• • Active acute or chronic infection requiring antimicrobial therapy, or serious viral infection (eg. hepatitis, herpes zoster).
• • Pregnant females, nursing mothers, or females not practicing birth control.
• • Patients with a single functioning kidney.
• • Pre-existent malignancy.
• • Insulin-treated diabetes mellitus.
• • GFR less than 25 ml/min/1.73m(2) BSA.
• • Known toxicity to cyclophosphamide.
• • Positive tests for HIV infection.
• Furthermore, patients with any one of the following conditions (related to the use of cyclosporin A) will be excluded from randomization within renal function group 2 (Glomerular filtration rate greater than 66 ml/min/1.73m(2)):
• • Renal biopsy revealing global sclerosis of greater than 50 percent of glomeruli, severe tubular atrophy, or severe interstitial fibrosis.
• • Persistently abnormal and unexplained liver function abnormalities (defined as elevated transaminases, bilirubin, or alkaline phosphatase twice the upper limit of normal for at least 1 month) or evidence of active viral hepatitis.
• • Hypertension difficult to control or uncontrollable with conventional anti-hypertensive regimens.
• • Documented coronary artery disease.
• • Convulsive disorders.