Clinical trial NCT06531824: EASi-KIDNEY™ (The Studies of Heart & Kidney Protection With BI 690517 in Combination With Empagliflozin)
Official title: A Multicenter, International, Randomized, Double-blind, Placebo-controlled Clinical Trial of the Aldosterone Synthase Inhibitor BI 690517 in Combination With Empagliflozin in Patients With Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Kidney Disease, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2024-08-01
Enrollment: 11000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: Run-in period, non randomized, single arm Part 2: Randomized (BI 690517 or placebo), double-blind, placebo-controlled follow-up period
Primary purpose: TREATMENT

Brief summary: This study is open to adults with chronic kidney disease at risk of progression. People with and without type 2 diabetes can take part in this study. The study is open to people who take other medicines called angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). People who already take empagliflozin or any other sodium-glucose cotransporter-2 inhibitor (SGLT2i) can also join. The study is also open to people who currently do not take any of these treatments. The purpose of this study is to find out whether a medicine called BI 690517 helps people with chronic kidney disease when taken in combination with a study medicine called empagliflozin. Worsening of kidney function increases the risk for kidney failure, cardiovascular disease, and heart disease.

This study has 2 parts. In the first part, participants get empagliflozin or placebo matching BI 690517 for at least 6 weeks. Participants continue taking ACEi or ARB throughout the study if such treatments are indicated. In the second part, participants are divided into 2 groups by chance. One group takes BI 690517 tablets and the other group takes placebo tablets. Placebo tablets look like BI 690517 tablets but do not contain any medicine. Participants take 1 tablet once a day in addition to empagliflozin for the duration of the study.

The doctors document when participants experience worsening of their kidney disease, go to hospital due to heart failure, or die of cardiovascular problems during the study. The time to these events is compared between the 2 treatment groups to see whether the treatment works. The study continues until the required number of events have occurred which is about 3 to 4 years. During this time, participants visit the study site about 4 times within the first 6 months. Then they visit the study site every 6 months. At the visits, doctors regularly check participants' health, take blood and urine samples, measure blood pressure and weight, check kidney function, and take note of any unwanted effects.


Eligibility criteria: Key Inclusion Criteria:

* Evidence of chronic kidney disease (CKD) at risk of kidney disease progression is defined on the basis of local laboratory results recorded at least 3 months before and at the time of the Screening visit, and requires:

  1. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR ≥20 \<45 mL/min/1.73m²; or
  2. CKD-EPI eGFR ≥45 \<90 mL/min/1.73m² with urine albumin-to-creatinine ratio (uACR) ≥200 mg/g (or protein-to-creatinine ratio ≥300 mg/g).
* Neither requires an Aldosterone Synthase inhibitor (ASi) or Mineralocorticoid Receptor Antagonist (MRA), nor that such treatment is definitely inappropriate.

Key Exclusion Criteria:

* Blood potassium of \>5.2 mmol/L at screening visit
* Blood Alanine Transaminase (ALT) or Aspartate Transaminase (AST) \>3x Upper Limit of Normal (ULN) at Screening visit
* Known liver cirrhosis
* On dialysis, functioning kidney transplant, or scheduled living donor transplant
* Treated with new immunosuppression therapy for new (or relapse/flare of pre-existing) kidney disease within the last 60 days
* Receiving more than one Renin-Angiotensin System (RAS) inhibitor (i.e. on dual therapy with two of an Angiotensin-Converting Enzyme inhibitor (ACEi), Angiotensin Receptor Blocker (ARB) or direct renin inhibitor)
* Currently treated with an Mineralocorticoid Receptor Antagonist (MRA) (e.g. spironolactone, eplerenone, finerenone)
* Currently treated with systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) Further exclusion criteria apply.

Primary outcomes:
measure: Time to first occurrence of the primary composite outcome of: (i) Kidney disease progression*; or (ii) Hospitalization for heart failure; or (iii) Cardiovascular death.
timeFrame: up to 4 years
Secondary outcomes:
measure: Key secondary outcome: Annual rate of change in eGFR from 3 month visit until last scheduled visit (i.e. chronic eGFR slope)
timeFrame: up to 4 years
measure: Time to first event of kidney failure, hospitalization for heart failure or cardiovascular death
timeFrame: up to 4 years
measure: Time to kidney disease progression
timeFrame: up to 4 years
measure: Occurrences of hospitalizations for heart failure (first and any subsequent, combined) or cardiovascular death
timeFrame: up to 4 years
measure: Occurrences of hospitalizations from any cause (first and any subsequent, combined)
timeFrame: up to 4 years
measure: Time to first event of kidney disease progression or cardiovascular death
timeFrame: up to 4 years
measure: Time to death from any cause
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Apogee Clinical Research
state: Alabama
city: Surprise
country: United States
facility: Southwest Kidney Institute
state: Arizona
city: Miami
country: United States
facility: Total Research Group, LLC
state: Florida
city: Coeur d'Alene
country: United States
facility: Kootenai Research Services
state: Idaho
city: Saint Joseph
country: United States
facility: Lake Michigan Nephrology
state: Michigan
city: Shelby
country: United States
facility: St. Clair Nephrology Research, LLC
state: Michigan
city: Portsmouth
country: United States
facility: Seacoast Kidney and Hypertension Specialists
state: New Hampshire
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates LLC
state: North Carolina
city: Upland
country: United States
facility: Clinical Renal Associates
state: Pennsylvania
city: East Providence
country: United States
facility: Nephrology Associates, Inc
state: Rhode Island
city: Lufkin
country: United States
facility: Texas Institute for Kidney and Endocrine Disorders
state: Texas
city: Pasadena
country: United States
facility: Renal Specialists of Houston, PA
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta Hospital (University of Alberta)
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital (Vancouver)
state: British Columbia
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital
city: København
country: Denmark
facility: Rigshospitalet, København
city: Roskilde
country: Denmark
facility: Zealand University Hospita; Roskilde
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, AöR
city: Bad Nenndorf
country: Germany
facility: Nephrologische Gemeinschaftspraxis Bad Nenndorf
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen
city: Berlin
country: Germany
facility: Praxis für Nierenkrankheiten und Dialyse Helle Mitte
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Elsenfeld
country: Germany
facility: Dialysezentrum Elsenfeld
city: Frankfurt am Main
country: Germany
facility: Agaplesion Markus Krankenhaus
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Frankfurt
country: Germany
facility: ClinPhenomics CVC GmbH
city: Freiburg
country: Germany
facility: Nierenzentrum Freiburg
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg, Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hannover
country: Germany
facility: Zentrum Für Nieren Hochdruck und Stoffwechselerkrankungen
city: Heilbronn
country: Germany
facility: BAG für Nephrologie und Dialyse
city: Homburg
country: Germany
facility: Universität des Saarlandes
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
city: Konstanz
country: Germany
facility: Klinikum Konstanz
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg AöR
city: München
country: Germany
facility: Klinikum der Universität München - Campus Innenstadt
city: Neckarsulm
country: Germany
facility: Dialysezentrum Neckarsulm
city: Rotenburg
country: Germany
facility: Dialysezentrum Rotenburg
city: Schweinfurt
country: Germany
facility: MVZ Dialysezentrum Schweinfurt
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus GmbH
city: Villingen-Schwenningen
country: Germany
facility: Nephrologisches Zentrum Villingen-Schwenningen
city: Wiesbaden
country: Germany
facility: Nierenzentrum Wiesbaden
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg AÖR
city: Bangalore
country: India
facility: Manipal Hospital
city: Bangalore
country: India
facility: St John's Medical College
city: Chandigarh
country: India
facility: Institute of Post Graduate Medical Education and Research
city: Hubballi
country: India
facility: Karnataka Medical college and research institute
city: Hyderabad
country: India
facility: Osmania Medical College & Hospital
city: Kozhikode
country: India
facility: IQRAA International hospital & research centre.
city: New Delhi
country: India
facility: Max Super Specialty Hospital, Saket
city: New Delhi
country: India
facility: Epitome Kidney Urology Institute and Lions Hospital
city: Patna
country: India
facility: Indira Gandhi Institute of Medical Sciences
city: Raipur
country: India
facility: All India Institute of Medical Sciences
city: Alessandria
country: Italy
facility: Ospedale Civile Ss. Antonio e Biagio
city: Asti
country: Italy
facility: Asti-Ospedale Cardinal Massaia
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Cagliari
country: Italy
facility: Azienda Ospedaliera ARNAS G. Brotzu
city: Cuneo
country: Italy
facility: A.S.O.S. Croce e Carle
city: Firenze
country: Italy
facility: Firenze-Ospedale San Giovanni di Dio
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Genova
country: Italy
facility: Azienda Ospedaliera San Martino
city: Milano
country: Italy
facility: Asst Santi Paolo E Carlo
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità
city: Parma
country: Italy
facility: Azienda Ospedaliera Unversitaria di Parma
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Prato
country: Italy
facility: Prato-Ospedale Santo Stefano
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
city: San Giovanni Rotondo (Foggia)
country: Italy
facility: IRCCS Ospedale "Casa Sollievo della Sofferenza"
city: Savona
country: Italy
facility: Azienda Sociosanitaria Ligure 2
city: Todi
country: Italy
facility: Todi-Nuovo Ospedale Media Valle del Tevere
city: Verbania
country: Italy
facility: Ospedale Castelli - Verbania
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
city: Batu Pahat
country: Malaysia
facility: Hospital Sultanah Nora Ismail
city: Georgetown
country: Malaysia
facility: Hospital Pulau Pinang-Pulau Pinang-21953
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
city: Kajang, Selangor
country: Malaysia
facility: Hospital Kajang
city: Klang
country: Malaysia
facility: Hospital Tengku Ampuan Rahimah
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Kuala Pilah
country: Malaysia
facility: Hospital Tuanku Ampuan Najihah
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Kulim
country: Malaysia
facility: Hospital Kulim
city: Melaka
country: Malaysia
facility: Hospital Melaka
city: Muar
country: Malaysia
facility: Hospital Pakar Sultanah Fatimah
city: Perai
country: Malaysia
facility: Hospital Seberang Jaya
city: Serdang
country: Malaysia
facility: Hospital Sultan Abdul Aziz Shah
city: Seremban
country: Malaysia
facility: Hospital Tuanku Ja'afar
city: Taiping
country: Malaysia
facility: Hospital Taiping
city: Teluk Intan
country: Malaysia
facility: Hospital Teluk Intan
city: Temerloh
country: Malaysia
facility: Hospital Sultan Haji Ahmad Shah
city: Porto
country: Portugal
facility: ULS de São João
city: Luodong Township
country: Taiwan
facility: Lotung Poh-Ai Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University-Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Municipal Wanfang Hospital
city: Belfast
country: United Kingdom
facility: South Eastern Health & Social Care Trust
city: Brighton
country: United Kingdom
facility: University Hospitals Sussex NHS Foundation Trusts
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Bury St Edmunds
country: United Kingdom
facility: West Suffolk NHS Foundation Trust
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
city: Chippenham
country: United Kingdom
facility: Hathaway Medical Centre
city: Clevedon
country: United Kingdom
facility: Clevedon Medical Centre
city: Dorset
country: United Kingdom
facility: Dorset County Hospital NHS Foundation Trust
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Pickering
country: United Kingdom
facility: Pickering Medical Practice
Study officials:
References: