Official Title: “Pentoxifylline and Progression of Chronic Kidney Disease in Moderate-to-High Risk Patients: a Pilot Randomized, Placebo-Controlled, Double-Blind Trial.”

The purpose of our study is to assess the impact of therapy with Pentoxifylline (PTF), a nonspecific phosphodiesterase inhibitor, on kidney function in patients at high-risk for progression to end-stage renal disease. We hypothesize that therapy with Pentoxifylline will slow progression of kidney disease over time.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

The treatment objective for chronic kidney disease (CKD), regardless of etiology, is to slow or halt progression of renal dysfunction and reduce proteinuria (in those patients with proteinuric renal disease). Multi-drug medical regimens remain the cornerstone of therapy for medical-renal disease, often with an angiotensin converting enzyme inhibitor and/or an angiotensin receptor blocker. These therapies, though often efficacious, have not been shown to halt disease progression entirely, and the medical therapy of renal disease remains suboptimal.

PTF is a safe, generally well-tolerated drug currently indicated for symptomatic and functional relief of intermittent claudication presumed due to chronic occlusive arterial disease of the limbs. A number of small studies in patients across a range of renal disease states show that PTF can reduce proteinuria, an important component of treatment of CKD. It is not known, however, if the drug will slow progression of CKD as measured by glomerular filtration rate.

Comparisons: subjects randomized to receive PTF compared with those randomized to receive placebo

Intervention(s) in this Clinical Trial

• Drug: Pentoxifylline

Primary Measures

• 1.Rate of decline in estimated glomerular filtration rate over one year

Secondary Measures

• 1. 50% reduction in proteinuria
• 2. Change in slope of 1/serum creatinine vs time

Inclusion Criteria:

• Patients 18 years of age or older currently being treated with an ACE-I or ARB and with one of the following conditions:
• 1. Non-nephrotic range proteinuria (between 1 and 3 grams/day by 24-hr collection), hypertension (blood pressure >130/80 or current use of antihypertensive drug therapy), and an eGFR of less than or equal to 40 ml/minute but greater than 20 ml/minute.

OR

• 2. Nephrotic range proteinuria (>=3 grams/day proteinuria) by 24-hr urine collection, and an eGFR greater than 20 ml/minute
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Exclusion Criteria:

• 1. Acute renal failure: defined by >25% decrease in eGFR over one month
• 2. Pregnancy or currently breast-feeding
• 3. Current use of cytotoxic drug therapy (cyclophosphamide, cyclosporine, mycophenolate mofetil, prednisone, chlorambucil) or a current indication for, and plan to implement, such therapy.
• 4. Current use of PTF
• 5. Contraindication to use of PTF drug: history of PTF or theophylline allergy, history of severe retinal hemorrhage or recent cerebral hemorrhage
• 6. Current use of theophylline
• 7. Contraindication to ACE-I or ARB.
• 8. Fewer than 2 measured serum creatinine values separated by 6 months prior to potential enrollment
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Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Walter Reed Army Medical Center

Overall Clinical Trial Officials and Contacts

Robert M Perkins, MD Study Director Walter Reed Army Medical Center, Nephrology Service  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00285298

Study ID Number: 05-11010(1)

ClinicalTrials.gov Identifier: NCT00285298

Health Authority: United States: Federal Government