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
aDepartment of Internal Medicine and Medical Specialties, Sapienza University, Rome, ItalybSection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, ItalycDepartment of Public Health and Infections Disease, Sapienza University of Rome, Roma, ItalydDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, ItalyeDepartment of Internal Medicine and Medical Specialties and DIBIMIS, School of Medicine, University of Palermo, Palermo, ItalyfDepartment Experimental Medicine–Medical Physiopathology, Food Science and Endocrinology Section, Sapienza University of Rome, Rome, ItalygDepartment of Medicine and Ageing, University of Chieti, Chieti, ItalyhDepartment of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
Checking for direct PDF access through Ovid
BackgroundType 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 11-dehydro-thromboxane (Tx)B2, 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.HypothesisThe 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-TxB2 will be related to renal function modifications.Study designA 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.SummaryThe 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 TxB2 production.