TY - JOUR

T1 - Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial

AU - Heerspink, H. J.L.

AU - Stefansson, B.

AU - Chertow, G.

AU - Correa-Rotter, R.

AU - Greene, Tom

AU - Hou, Fan Fan

AU - Lindberg, Magnus

AU - McMurray, John

AU - Rossing, P.

AU - Toto, Roberto

AU - Langkilde, Anna Maria

AU - Wheeler, David C.

AU - Heerspink, H. J.L.

AU - Wheeler, D. C.

AU - Chertow, G.

AU - Correa-Rotter, R.

AU - Greene, T.

AU - Hou, F. F.

AU - McMurray, J.

AU - Rossing, P.

AU - Toto, R.

AU - Stefansson, B.

AU - Langkilde, A. M.

AU - Pfeffer, Marc A.

AU - Pocock, Stuart

AU - Swedberg, Karl

AU - Rouleau, Jean L.

AU - Chaturvedi, Nishi

AU - Ivanovich, Peter

AU - Levey, Andrew S.

AU - Christ-Schmidt, Heidi

AU - Mann, Johannes

AU - Held, Claes

AU - Varenhorst, Christoph

AU - Holmgren, Pernilla

AU - Hallberg, Theresa

AU - Douthat, Walter

AU - Filho, Roberto Pecoits

AU - Cherney, David

AU - Hou, Fan Fan

AU - Persson, Frederik

AU - Haller, Hermann

AU - Wittmann, István

AU - Khullar, Dinesh

AU - Naoki, Kashihara

AU - Correa-Rotter, Richardo

AU - Escudero, Elizabeth

AU - Isidto, Rey

AU - Nowicki, Michal

AU - Batiushin, Mikhail

AU - DAPA-CKD Investigators

PY - 2020/2

Y1 - 2020/2

N2 - 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 m2 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 m2. 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 (a 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.

AB - 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 m2 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 m2. 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 (a 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.

KW - Chronic kidney disease

KW - Dapagliflozin

KW - Randomized controlled clinical trial

KW - Sodiumglucose co-transporter inhibitor

U2 - 10.1093/ndt/gfz290

DO - 10.1093/ndt/gfz290

M3 - Journal article

C2 - 32030417

AN - SCOPUS:85079082162

VL - 35

SP - 274

EP - 282

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

IS - 2

ER -