Effect of aspirin on renal disease progression in patients with type 2 diabetes: A multicenter, double-blind, placebo-controlled, randomized trial. The renaL disEase progression by aspirin in diabetic pAtients (LEDA) trial. Rationale and study design

Background Type 2 diabetes mellitus (T2DM) is one of the most common causes of chronic kidney disease and kidney failure. It has been estimated that the annual decline of estimated glomerular filtration rate (eGFR) among patients with T2DM is approximately 2.0-2.5 mL min(-1) y(-1). Cyclooxygenase-dependent eicosanoids, such as 1 1-dehydro-thromboxane (Tx)B-2, are increased in T2DM patients and are potentially involved in the regulation of renal blood flow. Animal models showed that cyclooxygenase inhibitors, such as aspirin, are associated with improvements in renal plasma flow and eGFR values. Hypothesis The primary end point of the LEDA trial is to evaluate the 1-year decline of eGFR in T2DM patients treated or not with low-dose aspirin (100 mg/d). Secondary end points will be the rapid decline in renal function, defined as a reduction of eGFR >= 5 mL/min, and change of renal function class after 1-year follow-up. Furthermore, urinary excretion 11-dehydro-TxB(2) will be related to renal function modifications. Study design A phase 3 no-profit, multicenter, double-blind, randomized intervention trial of aspirin 100 mg/dvs placebo (ClinicalTrials.gov Identifier: NCT02895113). All patients will be monitored at 6 and 12 months after randomization to assess drug adherence and eGFR changes. Summary The LEDA trial is the first double-blind, placebo-controlled, randomized clinical trial aimed at examining whether aspirin treatment may beneficially affect kidney function in patients with T2DM by reducing the annual eGFR decline. The trial will also examine whether the potential renoprotective effects of aspirin might be partly due to its inhibition of TxB(2) production.