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Clinical Trial
. 2023 Mar 31;38(4):894-903.
doi: 10.1093/ndt/gfac198.

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)

Jennifer B Green  1 , Amy K Mottl  2 , George Bakris  3 , Hiddo J L Heerspink  4 , Johannes F E Mann  5 , Janet B McGill  6 , Masaomi Nangaku  7 , Peter Rossing  8   9 , Charlie Scott  10 , Alain Gay  11 , Rajiv Agarwal  12
Affiliations
Clinical Trial

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)

Jennifer B Green et al. Nephrol Dial Transplant. .

Abstract

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.

Keywords: chronic kidney disease; diabetes; empagliflozin; finerenone; macroalbuminuria.

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Conflict of interest statement

The authors wrote the article with the assistance of a medical writer funded by the sponsor. The sponsor was involved in the study design and the writing of the report. J.B.G. has received grant support from Boehringer Ingelheim/Lilly, Merck, Roche and Sanofi/Lexicon and has been a consultant for Boehringer Ingelheim/Lilly, Bayer, AstraZeneca, Sanofi/Lexicon, Hawthorne Effect/Omada, Pfizer and NovoNordisk within the past 3 years. A.K.M. received research funding paid to her employer from Duke Clinical Research Institute, Pfizer, Aurinia, Alexion, Bayer and Calliditas and has received consultancy fees from Bayer, speaker fees from The Primary Care Consortium and royalties from UpToDate. G.B. reports receiving research funding from Bayer, Novo Nordisk and Vascular Dynamics, paid to the University of Chicago Miedicine; acting as a consultant and receiving personal fees from Alnylam, Merck and Relypsa; serving as an editor for the American Journal of Nephrology and Nephrology and Hypertension and as Section Editor for UpToDate; and serving as an associate editor for Diabetes Care. J.F.E.M. reports consultancy for AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Fresenius Medical Care, Novo Nordisk and Vifor Pharma; grants/grants pending for AbbVie, Boehringer Ingelheim, Canadian Institutes Health Research, Celgene, European Union, Isidoria, Novo Nordisk, Roche, Sanofi and Sandoz; and speaker bureaus for Amgen, AstraZeneca, Braun, Fresenius Medical Care, Gambro, Medice, Novo Nordisk and Roche. P.R. reports personal fees from Bayer, research support and personal fees from AstraZeneca and Novo Nordisk and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, MSD, Gilead and Sanofi. All fees are given to Steno Diabetes Centre Copenhagen. M.N. has received honoraria, advisory fees or research funding from Akebia, Alexion, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, GlaxoSmithKline, JT, Kyowa Hakko Kirin, Mitsubishi Tanabe, Ono, Takeda and Torii. H.J.L.H. reports grant funding and honoraria for consultancy as a member of the steering committee of the DAPA-CKD trial, paid to his institution, from AstraZeneca; research grants, paid to his employer, from AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk for clinical trials; consulting fees, paid to his employer, from AbbVie, Boehringer Ingelheim, Travere Pharmaceuticals and Novo Nordisk; fees for steering committee membership, paid to his employer, from Bayer, Chinook, CSL Pharma, Janssen and Gilead and honoraria for lectures from AstraZeneca and Mitsubishi Tanabe; and honoraria for advisory board participation for Merck (paid to his employer), Mitsubishi Tanabe and Mundipharma. J.B.M. reports personal fees from Bayer, Gilead, Mannkind and Provention Bio. She has received research support and personal fees from Novo Nordisk and research support from Dexcom, Beta Bionics and Medtronic. A.G. is an employee of Bayer AG, Germany. C.S. is an employee of Bayer PLC, UK. R.A. reports receiving personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals; receiving personal fees and nonfinancial support from Akebia Therapeutics, Boehringer Ingelheim, Eli Lilly and Vifor Pharma; serving as a member of data safety monitoring committees for Chinook and Vertex Pharmaceuticals; serving as a member of steering committees of randomized trials for Akebia Therapeutics and Bayer; serving as associate editor for the American Journal of Nephrology and Nephrology Dialysis and Transplantation and as an author for UpToDate; and receiving research grants from the US Veterans Administration and the National Institutes of Health.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Proposed mechanisms for reducing adverse cardiovascular- and kidney-related outcomes based on preclinical and clinical studies using finerenone and SGLT2 inhibitors.
Figure 2:
Figure 2:
Study design. The number of participants will be capped in parts A and B as follows: up to 80% with an eGFR ≤75 mL/min/1.73 m2 and up to 20% with an eGFR >75 mL/min/1.73 m2. Up-/down-titration based on eGFR, serum/plasma potassium or potassium, safety and tolerability. R, randomization.
See this image and copyright information in PMC

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