Francesco Violi1, Giovanni Targher2, Annarita Vestri3, Roberto Carnevale4, Maurizio Averna5, Alessio Farcomeni3, Andrea Lenzi6, Francesco Angelico3, Francesco Cipollone7, Daniele Pastori8. 1. Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy. Electronic address: francesco.violi@uniroma1.it. 2. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy. 3. Department of Public Health and Infections Disease, Sapienza University of Rome, Roma, Italy. 4. Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. 5. Department of Internal Medicine and Medical Specialties and DIBIMIS, School of Medicine, University of Palermo, Palermo, Italy. 6. Department Experimental Medicine-Medical Physiopathology, Food Science and Endocrinology Section, Sapienza University of Rome, Rome, Italy. 7. Department of Medicine and Ageing, University of Chieti, Chieti, Italy. 8. Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
Abstract
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 2.0-2.5mL 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. 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 (100mg/d). Secondary end points will be the rapid decline in renal function, defined as a reduction of eGFR ≥5mL/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 DESIGN: A phase 3 no-profit, multicenter, double-blind, randomized intervention trial of aspirin 100mg/dvs placebo (ClinicalTrials.gov Identifier: NCT02895113). All patients will be monitored at 6 and 12months 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 TxB2 production.
RCT Entities:
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 2.0-2.5mL 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. 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 (100mg/d). Secondary end points will be the rapid decline in renal function, defined as a reduction of eGFR ≥5mL/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 DESIGN: A phase 3 no-profit, multicenter, double-blind, randomized intervention trial of aspirin 100mg/dvs placebo (ClinicalTrials.gov Identifier: NCT02895113). All patients will be monitored at 6 and 12months 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 TxB2 production.
Authors: Patrizia Natale; Suetonia C Palmer; Valeria M Saglimbene; Marinella Ruospo; Mona Razavian; Jonathan C Craig; Meg J Jardine; Angela C Webster; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2022-02-28
Authors: Kevan R Polkinghorne; James B Wetmore; Le Thi Phuong Thao; Rory Wolfe; Robyn L Woods; Michael E Ernst; Mark R Nelson; Christopher M Reid; Raj C Shah; John J McNeil; Anne M Murray Journal: Am J Kidney Dis Date: 2022-04-14 Impact factor: 11.072