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
Authors: Agarwal Rajiv , Green Jennifer B , Heerspink Hiddo J L , Mann Johannes F E , McGill Janet B , Mottl Amy K , Rosenstock Julio , Rossing Peter , Vaduganathan Muthiah , Brinker Meike , Edfors Robert , Li Na , Scheerer Markus F , Scott Charlie , Nangaku Masaomi ,   for the CONFIDENCE investigators, Consoli Agostino , Awad Ahmed , Arduan Alberto Ortiz , Soto Alfonso , Iranmanesh Ali , Mottl Amy K , Nollet An , Doshi Ankur , Veronelli Anna Maria Grazia , Patel Architkumar , Luqman Ashar , Balasubramaniyan T , Winkelmann Bernhard , Baker Bruce , Guerci Bruno , Van Vlem Bruno , Verges Bruno , Lee Byung Wan , Solis-Herrera Carolina , Matad Chandrashekar , Lee Chang Beom , Lee Chien-Te , Chang Chiz-Tzung , Chung Choon-Hee , Kloos Christof , Axthelm Christoph , Juhl Claus , Castro Cristina , Morales Cristobal , Kovesdy Csaba , Yamada Daishiro , Mitchell Dana , Gaskin David , LaMond David , Tarng Der-Cherng , Khullar Dinesh , Carron Pierre-Louis , Sahay Manisha , Sahyouni Elie , Bosi Emanuele , Fiaccadori Enrico , Lee EunYoung , Adawi Faiad , Castro Fernando Cereto , Duyck Francis , Deben Francisco Martinez , Madueno Francisco Tinahones , Umeoka Fumi , Bantwal Ganapathi , Aharon-Hananel Genya , Hernandez German , Tonolo Giancarlo , Mazza Giuseppe , Penno Giuseppe , Ortiz Gloria , Umpierrez Guillermo , Bourarich Hanane , Alva Hansraj , Miller Harold , Serota Harvey , Kanehara Hideo , Kanai Hidetoshi , Mehta Hitesh , Liberty Idit , Khalid Iqbal , Yu Jae-Myung , Probst Jared , Sandberg Jay , Shubrook Jay , Jayakumar E K , Fauvel Jean-Pierre , van der Net Jeroen , Bech Jesper Nørgaard , Teruel Jose Luis Górriz , Mandry Jose , Ravid Joseph , Mediavilla Juan Diego , Gupta Jugal Bihari , Silverstein Julie , Wainstein Julio , Jiang Ju-Ying , Keshavamurthy C B , Lee Keung , Busch Klaus , Kobayashi Kunihisa , Spry Leslie , Stemler Lutz , Wu Mai-Szu , Romeo Maria Jose Soler , Vidas Maria Marques , Garcia-Touza Mariana , Speeckaert Marijn , van der Giet Markus , Ochi Masahiko , Ishii Masao , Ray Matthew , Elias Mazen , Rajpal Minesh , Wu Ming Ju , Lips Mirjam , El-Shahawy Mohamed , Shahid Nauman , Assy Nimer , Levin-Iaina Nomy , Dupuy Olivier , Moranne Olivier , Brusco Osvaldo , Pergola Pablo , Atanu Pal , Ponzani Paola , Rootjes Paul , Mieyer Pedro Velasquez , Doubel Peter , Luik Peter , Rossing Peter , Gillard Pieter , Lazowski Piotr , Ratna Prabha Dadala , Singh Raj , John Rekha , Powell Richard , Tytus Richard , Poli Roberta , Cimino Roberto , Trevisan Roberto , De Cosmo Salvatore , Chaubey Sameer , Fikry Sameh , Agarwal Sanjay Chunilal , Agarwal Saurabh , Hines Scott , Peterson Sean , Shin Seok Joon , Balram Sharma , Tu Shih-Te , Jolly Shivinder , Mavani Siddharth , Lim Soo , Raju Sree Bhushan , Reddy Sreedhar , Fordan Steve , Wangnoo Subhash , Kim Sung-Gyun , Pervaiz Syed , Osonoi Takeshi , Hayashi Terumasa , Koch Thorsten , Krarup Thure , Tran Tuan-Huy , Bandgar Tushar , Ritesh Vernekar , Resi Veronica , Al-Shweiat Wajdi , Kotzker Wayne , Beaubien-Souligny William , Kaye William , Yang William , Lee Woo-Je , Hirohata Yoshihide , Yamasaki Yoshimitsu , Hwang You-Cheol , Cho Young Min , Kang Young Sun 
Published: January 2025

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 &lt;5000 mg/g. Participants taking the clinically maximum tolerated dose of a renin–angiotensin system inhibitor for &gt;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 (&lt; or ≥60 ml/min/1.73 m2) and UACR (≤ or &gt;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.