COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint (CONFIDENCE) trial: Baseline clinical characteristics.

Abstract

Background and hypothesis: Finerenone, a selective nonsteroidal MRA, and SGLT2is both reduce CKD progression and improve kidney/CV outcomes. The CONFIDENCE study (NCT05254002; EudraCT 2021-003037-11) hypothesis is that early combination of finerenone and empagliflozin, a SGLT2i, is superior to either drug alone in reducing UACR over 6 months.

Methods: CONFIDENCE is an ongoing, fully enrolled, randomized, controlled, double-blind, multicentre phase 2 clinical trial in adults (≥18 years of age) with CKD and T2D, eGFR of 30 to 90 ml/min/1.73 m2, and UACR of ≥100 to <5000 mg/g. Participants taking the clinically maximum tolerated dose of a renin-angiotensin system inhibitor for >1 month at screening were eligible. Participants were randomized 1:1:1 to once daily finerenone plus empagliflozin, finerenone plus placebo, or empagliflozin plus placebo; doses were 10 mg once daily for empagliflozin and 10 or 20 mg once daily for finerenone, depending on eGFR at baseline. Randomization was stratified by eGFR (< or ≥60 ml/min/1.73 m2) and UACR (≤ or >850 mg/g). The primary efficacy outcome is the relative change in UACR from baseline at Day 180.

Results: There were 818 participants randomized across 143 sites from 14 countries between July 2022 and August 2024. Mean eGFR (ml/min/1.73 m2 [SD]) was 54.2 (17.1). Median UACR (mg/g [IQR]) was 583 (292, 1140). Mean HbA1c (% [SD]) was 7.3 (1.2). Mean systolic/diastolic BP (mmHg) was 135.2/77.3. GLP-1 RAs and insulin were used by 182 (23%) and 313 (39%) participants, respectively. Atherosclerotic CV disease, diabetic retinopathy, and a history of heart failure were present in 223 (28%), 126 (16%), and 30 (4%) participants, respectively.

Conclusions: The CONFIDENCE trial enrolled a diverse population with CKD and T2D and will determine the impact of simultaneous initiation of combination finerenone and a SGLT2i versus individual therapy on potentially mitigating the progression of CKD in people with T2D. Trial registration number: Clinicaltrials.gov NCT05254002; EudraCT 2021-003037-11.