Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Issue 2 (7th February 2020)

• Record Type: Journal Article
• Authors: Heerspink, Hiddo J L; Stefansson, Bergur V; Chertow, Glenn M; Correa-Rotter, Ricardo; Greene, Tom; Hou, Fan-Fan; Lindberg, Magnus; McMurray, John; Rossing, Peter; Toto, Roberto; Langkilde, Anna Maria; Wheeler, David C
• Is Part Of: Nephrology dialysis transplantation. Volume 35:Issue 2(2020)
• Page Start: 274
• Page End: 282
• Publication Date: 2020-02-07
• Subjects: chronic kidney disease -- dapagliflozin -- randomized controlled clinical trial -- sodium–glucose co-transporter inhibitor; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfz290
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background: Recent cardiovascular outcome trials have shown that sodium–glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. Methods: DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2–4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin–angiotensin system inhibitor at enrolment. Results: After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m 2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m 2 . The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). Conclusion: DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes. Graphical Abstract: