Related Experiment Videos
The Veterans Affairs Pentoxifylline in Diabetic Kidney Disease (VA PTXRx) Study: Baseline Characteristics
David J Leehey1, Rajiv Agarwal2, Bin Xing3
1Edward Hines, Jr. VA Medical Center, Hines, IL, USA.
Introduction:
Experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) reduces proteinuria and may delay the progression of diabetic kidney disease (DKD). However, no large-scale randomized clinical trial has determined whether PTX can reduce end-stage kidney disease (ESKD) and mortality in DKD.
Design:
VA PTXRx is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial designed to test the hypothesis that PTX, when added to usual care, prolongs the time to kidney failure or death in type 2 diabetic (T2D) participants with DKD compared to usual care plus placebo. Enrolled participants at very high risk for ESKD and/or death were randomized in a 1:1 ratio to either PTX 400 mg twice daily or matching placebo using randomly permuted blocks with stratification for site, renin-angiotensin-aldosterone (RAAS) inhibitor use, and chronic kidney disease (CKD) stage. The study is event-driven, requiring 646 primary events (ESKD (chronic dialysis or transplantation) or death) to achieve 80% power to detect a relative risk reduction of 19% with PTX.
Baseline Results:
Between December 2019 and November 2025, 2376 participants at 34 VA sites in the USA were randomized. The mean age at randomization was 72.3 years (SD 7.7), with 97% being male. The mean baseline eGFR was 33.3 mL/min/1.73 m2 (SD 9.4). The median urinary albumin to creatinine ratio (UACR) was 401 mg/g (IQR 122-1076). At baseline, the usage of RAAS inhibitors was 80.0%, sodium-glucose transporter-2 (SGLT2) inhibitors 52.9%, glucagon-like peptide-1 (GLP-1) receptor agonists 33.2%, and finerenone 3.0%. The majority (88%) of participants had stage 3B or 4 CKD (eGFR < 45 mL/min/1.73m2).
Conclusions:
The results, anticipated in 2027, are expected to determine whether PTX is a treatment option for patients with high-risk DKD. Because PTX is a generic medication, it is inexpensive in many health systems, which would facilitate access if it proves effective. Trial Registration: This study is registered with clinicaltrials.gov (Identifier: NCT03625648).
