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

Pentoxifylline and Progression of Chronic Kidney Disease in Moderate-to-high Risk Patients: a Pilot Randomized, Placebo-controlled, Double-blind Trial.

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.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Pentoxifylline

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Pentoxifylline	Drug: Pentoxifylline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of decline in estimated glomerular filtration rate over one year	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
50% reduction in proteinuria	1 year
Change in slope of 1/serum creatinine vs time	1 year

Collaborators and Investigators

• Sponsor: Walter Reed Army Medical Center
• Collaborators: National Kidney Foundation
• Investigators: Study Director: Robert M Perkins, MD, Walter Reed Army Medical Center, Nephrology Service

Publications and helpful links

General Publications

• Perkins RM, Aboudara MC, Uy AL, Olson SW, Cushner HM, Yuan CM. Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial. Am J Kidney Dis. 2009 Apr;53(4):606-16. doi: 10.1053/j.ajkd.2008.11.026. Epub 2009 Feb 12.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: January 31, 2006
• First Submitted That Met QC Criteria: January 31, 2006
• First Posted (Estimate): February 1, 2006

Study Record Updates

• Last Update Posted (Estimate): July 29, 2011
• Last Update Submitted That Met QC Criteria: July 28, 2011
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: proteinuria; Kidney failure, chronic
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: 05-11010(1); 11010A (NKF)