Kidney Week

Abstract: SA-PO154

Design of Pentoxifylline in Diabetic Kidney Disease (VA PTXRx)

Session Information

• Diabetic Kidney Disease: Clinical - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Leehey, David J., Hines VA Hospital, Hines, Illinois, United States

David J. Leehey,

• Craig, Ian, Perry Point Cooperative Studies Program Coordinating Center, Perryville, Maryland, United States

Ian Craig,

• Reda, Domenic, Hines VA Cooperative Studies Program Coordinating Center, Hines, Illinois, United States

Domenic Reda,

• Carlson, Kim, Hines VA Cooperative Studies Program Coordinating Center, Hines, Illinois, United States

Kim Carlson,

• Conner, Todd A., VA CSP CRPCC, Albuquerque, New Mexico, United States

Todd A. Conner,

• Agarwal, Rajiv, Roudebush VA Hospital, Indianapolis, Indiana, United States

Rajiv Agarwal,

• Kaufman, James S., VA New York Harbor Healthcare System, New York, New York, United States

James S. Kaufman,

• Anderson, Robert, Omaha VA Hospital, Omaha, Nebraska, United States

Robert Anderson,

• Huang, Grant D., Director, Cooperative Studies Program (CSP), Washington, District of Columbia, United States

Grant D. Huang,

• Emanuele, Nicholas, Hines VA Hospital, Hines, Illinois, United States

Nicholas Emanuele,

Background

Diabetic kidney disease (DKD) is the most frequent cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the U.S. Despite control of blood pressure and blockade of the renin-angiotensin-aldosterone system (RAAS), many patients continue to progress to ESRD, requiring costly dialysis or transplantation and resulting in high mortality. The non-specific phosphodiesterase inhibitor pentoxifylline (PTX) was approved by the FDA in 1984 for the treatment of peripheral vascular disease. Recent experimental and clinical data suggest that PTX, when added to usual care, leads to a reduction in albuminuria and inflammation and may decrease progression of DKD. However, a large scale multicenter randomized clinical trial is needed to determine whether this agent can reduce hard endpoints such as ESRD and death in patients with DKD.

Methods

VA PTXRx is a randomized, controlled multicenter Veterans Affairs (VA) Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the incidence of ESRD and death in type 2 diabetic patients with DKD when compared to usual care plus placebo. Secondary endpoints will be: (1) quality of life (2) time until doubling of serum creatinine, (3) hospitalization for congestive heart failure (CHF), (4) a three-point MACE (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) peripheral vascular disease (PVD), (6) percentage of participants with ≥ 50% reduction in urinary albumin-to-creatinine ratio (UACR) from baseline, (7) Rate of change in estimated glomerular filtration rate (eGFR) per year during the study period. Drug safety will also be analyzed as a secondary outcome. The key statistical assumption is that the primary endpoint will occur in 26.6% of the placebo group at six years with a risk reduction of 19% for PTX compared with the placebo group. The study aims to randomize 2510 participants to either PTX or placebo. The expected event rates were estimated using retrospective data from a cohort of veterans meeting study inclusion criteria obtained from a nationwide VA database.

Results

N/A

Conclusion

If PTX is found to reduce the incidence of ESRD and/or death with an acceptable safety profile, this will reduce the personal and financial burden of renal replacement therapy for patients with DKD.

Funding

• Veterans Affairs Support