TY - JOUR

T1 - Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE)

AU - Green, Jennifer B.

AU - Mottl, Amy K.

AU - Bakris, George

AU - Heerspink, Hiddo J.L.

AU - Mann, Johannes F.E.

AU - Mcgill, Janet B.

AU - Nangaku, Masaomi

AU - Rossing, Peter

AU - Scott, Charlie

AU - Gay, Alain

AU - Agarwal, Rajiv

N1 - Publisher Copyright: © 2022 The Author(s).

PY - 2023

Y1 - 2023

N2 - Background: Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone. Methods: CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a urine albumin:creatinine ratio (UACR) ≥300-<5000 mg/g. The primary objective is to demonstrate that 6 months of dual therapy comprising finerenone and the SGLT2i empagliflozin is superior for reducing albuminuria versus either agent alone. Interventions will be once-daily finerenone 10 mg or 20 mg (target dose) plus empagliflozin 10 mg, or empagliflozin 10 mg alone, or finerenone 10 mg or 20 mg (target dose) alone. Results: The primary outcome is a relative change from baseline in UACR among the three groups. Secondary outcomes will further characterize efficacy and safety, including changes in estimated glomerular filtration rate and incident hyperkalemia. Conclusions: CONFIDENCE is evaluating the safety, tolerability and efficacy of dual use of finerenone and an SGLT2i in adults with CKD and T2D. Should an additive effect be shown, early and efficient intervention with dual finerenone and SGLT2i therapy could slow disease progression and provide long-term benefits for people with CKD and T2D.

AB - Background: Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone. Methods: CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a urine albumin:creatinine ratio (UACR) ≥300-<5000 mg/g. The primary objective is to demonstrate that 6 months of dual therapy comprising finerenone and the SGLT2i empagliflozin is superior for reducing albuminuria versus either agent alone. Interventions will be once-daily finerenone 10 mg or 20 mg (target dose) plus empagliflozin 10 mg, or empagliflozin 10 mg alone, or finerenone 10 mg or 20 mg (target dose) alone. Results: The primary outcome is a relative change from baseline in UACR among the three groups. Secondary outcomes will further characterize efficacy and safety, including changes in estimated glomerular filtration rate and incident hyperkalemia. Conclusions: CONFIDENCE is evaluating the safety, tolerability and efficacy of dual use of finerenone and an SGLT2i in adults with CKD and T2D. Should an additive effect be shown, early and efficient intervention with dual finerenone and SGLT2i therapy could slow disease progression and provide long-term benefits for people with CKD and T2D.

KW - chronic kidney disease

KW - diabetes

KW - empagliflozin

KW - finerenone

KW - macroalbuminuria

U2 - 10.1093/ndt/gfac198

DO - 10.1093/ndt/gfac198

M3 - Journal article

C2 - 35700142

AN - SCOPUS:85138315074

VL - 38

SP - 894

EP - 903

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

IS - 4

ER -