Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Kidney Function in Advanced Chronic Kidney Disease

Summary

The goal of this clinical trial is to evaluate whether dapagliflozin can reduce the risk of worsening kidney function or death from cardiovascular or renal causes in adults with advanced chronic kidney disease (CKD), with or without type 2 diabetes. The main questions it aims to answer are: 1. Does dapagliflozin reduce the rate of decline in kidney function or progression to end-stage kidney disease in adults with advanced CKD? 2. Does dapagliflozin reduce the risk of death from cardiovascular or renal causes in patients with advanced CKD? Researchers will compare dapagliflozin to a placebo to see if dapagliflozin improves kidney and cardiovascular outcomes in this high-risk population.

Timeline

Start

2025-05-01

Primary completion

2026-06-01

Completion

2026-11-01

Publications

• Background Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018. No abstract available.
• Background Roddick AJ, Wonnacott A, Webb D, Watt A, Watson MA, Staplin N, Riding A, Lioudaki E, Kuverji A, Kossi ME, Holmes P, Holloway M, Fraser D, Carvalho C, Burton JO, Bhandari S, Herrington WG, Frankel AH. UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE. BMC Nephrol. 2023 Oct 25;24(1):310. doi: 10.1186/s12882-023-03339-3.
• Background Moral Berrio E, De La Flor JC, Arambarri Segura M, Rodriguez-Doyaguez P, Martinez Calero A, Zamora R, Cieza-Terrones M, Yuste-Lozano C, Sanchez de la Nieta Garcia MD, Nieto Iglesias J, Vozmediano Poyatos C. Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data. Medicina (Kaunas). 2024 Jul 24;60(8):1198. doi: 10.3390/medicina60081198.
• Background Levey AS, Gansevoort RT, Coresh J, Inker LA, Heerspink HL, Grams ME, Greene T, Tighiouart H, Matsushita K, Ballew SH, Sang Y, Vonesh E, Ying J, Manley T, de Zeeuw D, Eckardt KU, Levin A, Perkovic V, Zhang L, Willis K. Change in Albuminuria and GFR as End Points for Clinical Trials in Early Stages of CKD: A Scientific Workshop Sponsored by the National Kidney Foundation in Collaboration With the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis. 2020 Jan;75(1):84-104. doi: 10.1053/j.ajkd.2019.06.009. Epub 2019 Aug 28.
• Background Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet. 2021 Aug 28;398(10302):786-802. doi: 10.1016/S0140-6736(21)00519-5. Epub 2021 Jun 24.
• Background Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, Crews DC, Doria A, Estrella MM, Froissart M, Grams ME, Greene T, Grubb A, Gudnason V, Gutierrez OM, Kalil R, Karger AB, Mauer M, Navis G, Nelson RG, Poggio ED, Rodby R, Rossing P, Rule AD, Selvin E, Seegmiller JC, Shlipak MG, Torres VE, Yang W, Ballew SH, Couture SJ, Powe NR, Levey AS; Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021 Nov 4;385(19):1737-1749. doi: 10.1056/NEJMoa2102953. Epub 2021 Sep 23.
• Background Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
• Background Heerspink HJL, Sjostrom CD, Jongs N, Chertow GM, Kosiborod M, Hou FF, McMurray JJV, Rossing P, Correa-Rotter R, Kurlyandskaya R, Stefansson BV, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial. Eur Heart J. 2021 Mar 31;42(13):1216-1227. doi: 10.1093/eurheartj/ehab094.
• Background Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M, Pletcher MA, Smith AE, Tang K, Yuan CW, Brown JC, Friedman J, He J, Heuton KR, Holmberg M, Patel DJ, Reidy P, Carter A, Cercy K, Chapin A, Douwes-Schultz D, Frank T, Goettsch F, Liu PY, Nandakumar V, Reitsma MB, Reuter V, Sadat N, Sorensen RJD, Srinivasan V, Updike RL, York H, Lopez AD, Lozano R, Lim SS, Mokdad AH, Vollset SE, Murray CJL. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018 Nov 10;392(10159):2052-2090. doi: 10.1016/S0140-6736(18)31694-5. Epub 2018 Oct 16.
• Background Dobre M. Safety of SGLT2 Inhibitors in CKD: Walking the Fine Line. Clin J Am Soc Nephrol. 2022 Jun;17(6):774-776. doi: 10.2215/CJN.04900422. Epub 2022 May 26. No abstract available.
• Background De La Flor JC, Villa D, Cruzado L, Apaza J, Valga F, Zamora R, Marschall A, Cieza M, Deira J, Rodeles M. Efficacy and Safety of the Use of SGLT2 Inhibitors in Patients on Incremental Hemodialysis: Maximizing Residual Renal Function, Is There a Role for SGLT2 Inhibitors? Biomedicines. 2023 Jul 6;11(7):1908. doi: 10.3390/biomedicines11071908.
• Background Chertow GM, Vart P, Jongs N, Toto RD, Gorriz JL, Hou FF, McMurray JJV, Correa-Rotter R, Rossing P, Sjostrom CD, Stefansson BV, Langkilde AM, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. J Am Soc Nephrol. 2021 Sep;32(9):2352-2361. doi: 10.1681/ASN.2021020167. Epub 2021 Jul 16.
• Background Barreto J, Borges C, Rodrigues TB, Jesus DC, Campos-Staffico AM, Nadruz W, Luiz da Costa J, Bueno de Oliveira R, Sposito AC. Pharmacokinetic Properties of Dapagliflozin in Hemodialysis and Peritoneal Dialysis Patients. Clin J Am Soc Nephrol. 2023 Aug 1;18(8):1051-1058. doi: 10.2215/CJN.0000000000000196. Epub 2023 May 25.

Drugs

Indications