The Veterans Affairs Pentoxifylline in Diabetic Kidney Disease (VA PTXRx) Study: Baseline Characteristics.

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).