Pentoxifylline and Progression of Chronic Kidney Disease in Moderate-to-high Risk Patients

Phase 3

Completed

• Conditions: Kidney Failure, Chronic
• Interventions: Drug: Placebo; Drug: Pentoxifylline

• Registration Number: NCT00285298
• Lead Sponsor: Walter Reed Army Medical Center

Brief Summary

The purpose of the investigators 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. The investigators hypothesize that therapy with Pentoxifylline will slow progression of kidney disease over time.

Detailed Description

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

Study Timeline

• Study Start: 2006-01
• Study First Submitted: 2006-01-31
• Study First Submitted QC: 2006-01-31
• Study First Posted: 2006-02-01
• Primary Completion: 2008-04
• Study Completion: 2008-04
• Status Verified: 2009-09
• Last Update Submitted: 2011-07-28
• Last Update Posted: 2011-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Pentoxifylline	Pentoxifylline	-

Primary Outcome Measures

Name	Time	Method
Rate of decline in estimated glomerular filtration rate over one year	1 year

Secondary Outcome Measures

Name	Time	Method
50% reduction in proteinuria	1 year
Change in slope of 1/serum creatinine vs time	1 year