Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
This study will examine the effectiveness of the drug pirfenidone in treating focal segmental glomerulosclerosis (FSGS). Patients with this disease have kidney fibrosis (scarring) and proteinuria (excessive excretion of protein in the urine). About half of patients with FSGS eventually require kidney dialysis or transplant. Steroids, which are currently used to treat the disease, are effective in only a minority of patients. Other drugs, such as cyclosporin and cyclophosphamide, improve proteinuria in a very small percentage of patients and have serious side effects.
Patients with FSGS who wish to participate in this study will undergo pre-study evaluation with blood and urine tests. Patients must be on a stable dose of an ACE inhibitor (a drug that lowers blood pressure and reduces proteinuria) for at list 6 months before starting pirfenidone therapy. (Patients who are not already taking an ACE inhibitor will be started on the drug; those who cannot tolerate ACE inhibitors will be given a different drug.) Patients with elevated cholesterol will take a cholesterol-lowering drug. A diet containing approximately 1 gram of protein per kilogram of body weight per day will be recommended.
Patients will take pirfenidone by mouth 3 times a day for 12 months. Blood and urine will be tested once a month, either at NIH or by the patient's local kidney specialist. They will collect two 24-hour urine samples at the beginning of the treatment period, at 2-month intervals throughout the study, and at a 6-month follow-up. Patients will also be asked to give three to five tubes of blood and urine samples for analysis during the study.
In animal studies, pirfenidone improved kidney function and proteinuria and reduced kidney scarring in rats with a disease similar to FSGS. In human studies, pirfenidone improved breathing and survival in patients with lung fibrosis.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pirfenidone in Focal Segmental Glomerulosclerosis:Phase II Study|
- Decrease in GFR During Treatment Period [ Time Frame: 12 months from baseline ] [ Designated as safety issue: No ]
- Proteinuria After Treatment [ Time Frame: 12 months from baseline ] [ Designated as safety issue: No ]
- Proportion of Patients With Positive Change in GFR [ Time Frame: 12 months from baseline ] [ Designated as safety issue: No ]
|Study Start Date:||December 1999|
|Study Completion Date:||October 2008|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
The objective of this pilot phase II trial is to evaluate the ability of pirfenidone, a novel anti-fibrotic agent, to reduce the proteinuria and slow the rate of progression of renal insufficiency in patients with focal segmental glomerulosclerosis (FSGS). We will enroll 25 patients with renal biopsy proven FSGS and evidence of impaired renal function (GFR of 10-80 cc/min; after 1/02 must have GFR greater than 25 ml/min) as assessed by the 4 variable MDRD equation. As standard of care therapy, all patients will also receive angiotensin converting enzyme inhibitor (ACEI) therapy, and will receive an HMG Co-A reductase inhibitor drug if hypercholesterolemic. Preliminary evaluation will assure that the patients meet the study requirements, and an evaluation period will be used to ensure that patients are on maximal conservative therapy prior to the baseline period. Patients will receive treatment with pirfenidone daily, with dose adjusted for body weight and level of kidney function. The primary end point will be rate of change of glomerular filtration as a marker of glomerular injury; effect on proteinuria will be a secondary end-point. If the pilot study suggests this drug delays progression of renal insufficiency or reduces proteinuria in patients with FSGS, we will proceed with a large scale randomized, placebo-controlled study.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|