Clinical trial NCT00285298: Pentoxifylline and Progression of Chronic Kidney Disease in Moderate-to-high Risk Patients
Official title: Pentoxifylline and Progression of Chronic Kidney Disease in Moderate-to-high Risk Patients: a Pilot Randomized, Placebo-controlled, Double-blind Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Failure, Chronic
Keywords: proteinuria
Kidney failure, chronic
Lead sponsor: Walter Reed Army Medical Center
Sponsor class: FED
Collaborators: name: National Kidney Foundation, United States
First posted: 2006-02-01
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Rate of decline in estimated glomerular filtration rate over one year
timeFrame: 1 year
Secondary outcomes:
measure: 50% reduction in proteinuria
timeFrame: 1 year
measure: Change in slope of 1/serum creatinine vs time
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Walter Reed Army Medical Center, Nephrology Service
name: Robert M Perkins, MD
role: STUDY_DIRECTOR
References:
citation: 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.