Evaluation of the Risk of Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes Mellitus

July 17, 2026 updated by: Aeterna Medical Solutions SL

Implication of Albuminuria Reduction and Other Cardiorenal Effects on The Risk of Heart Failure in Patients With CKD and T2D

The goal of this study, performed entirely with computer programs, is to learn if using a combination of two drugs works better than using one alone, in the treatment of people with chronic kidney disease and type 2 diabetes mellitus.

The main questions it aims to answer are:

  • How many events of heart failure, heart failure hospitalizations, and cardiovascular death happen in each group?
  • How do serious kidney problems progress in each of the groups?

Researchers will compare reference therapy (finerenone) with a combination of finerenone and empagliflozin.

There will not be human participants in this study. With the help of artificial intelligence, researchers will recreate a large population of people with chronic kidney disease and type 2 diabetes mellitus. Data on their disease, treatment, and laboratory parameters will be based on and simulated using real data from previous clinical trials conducted with real participants.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Traditional risk stratification tools, such as the PREVENT (Predicting Risk of cardiovascular disease EVENTs) equations, estimate 10-year risk using static baseline variables. Simply adjusting the UACR input in the PREVENT calculator offers only a crude approximation and does not capture the dynamic, nonlinear effects of ongoing pharmacological treatment, biological hysteresis, and competing risks. To address these limitations, we will develop a high-fidelity digital twin simulation framework powered by the Aeterna Deep computational engine. This in silico trial will project 10-year cardio-renal outcomes for finerenone, empagliflozin, and their combination, while quantifying the mechanistic contribution of UACR reduction relative to other cardio-renal factors. The reference population will be defined according to the CONFIDENCE trial criteria, including adults with chronic kidney disease (eGFR 30-90 ml/min/1.73 m²), type 2 diabetes, and persistent albuminuria (UACR 100-5000 mg/g), receiving maximally tolerated renin-angiotensin system inhibitors. From this base, a synthetic cohort of 100,000 digital twins will be constructed using a four phase instantiation framework designed to ensure biological plausibility. First, marginal distributions for key demographic and clinical variables (age, sex, eGFR, UACR, blood pressure, HbA1c) will be parameterized from validated real-world datasets. Second, nonlinear physiological interdependencies will be reconstructed through multivariate coupling functions to preserve the in vivo covariance structure. Third, individual phenotypes will be generated via high-dimensional stochastic sampling to capture the full range of cardio renal metabolic trajectories. Finally, all instantiated profiles will undergo thermodynamic and biophysical truncation, whereby parameter combinations violating conservation principles or exceeding human homeostatic limits will be excluded and regenerated, ensuring that only physiologically viable digital entities will be retained for downstream analyses.

Study Type

Observational

Enrollment (Estimated)

50000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

A massive synthetic cohort (N = 50,000 to 100,000 virtual subjects) will be structured and parameterized to faithfully reproduce the characteristics of the reference population, using a four-phase instantiation framework designed to ensure biological plausibility. Each virtual patient will be cloned to experience both treatment trajectories simultaneously, acting as their own absolute control and eliminating inter-individual variability bias.

Description

Inclusion Criteria: The same characteristics of the reference population: CONFIDENCE trial (NCT05254002). In brief:

  • Patients with chronic kidney disease (eGFR 30-90 ml/min/1.73 m²)
  • Persistent albuminuria (UACR 100-5000 mg/g)
  • Type 2 diabetes mellitus (T2D) under stable blockade of the renin-angiotensin system (ACEi/ARB)

Exclusion Criteria: The same characteristics of the reference population: CONFIDENCE trial (NCT05254002). In brief:

  • Participants with type 1 diabetes (T1D).
  • Participant with hepatic insufficiency classified as Child-Pugh C.
  • Participants currently treated or who were treated with Finerenone (Kerendia©) within 8 weeks prior to the screening visit.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Reference Monotherapy
Finerenone
Early Combo Strategy
Concomitant combination of finerenone and empagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to First Occurrence of Incident Heart Failure, Heart Failure Hospitalization, or Cardiovascular Death
Time Frame: From the beginning of the simulation up to 10 years
Composite endpoint including incident heart failure, heart failure hospitalization, and cardiovascular death. Purely atherothrombotic events (myocardial infarction and ischemic stroke) are excluded from this composite variable.
From the beginning of the simulation up to 10 years
Time to Onset of End-Stage Kidney Disease, Sustained eGFR <15 ml/min/1.73 m², or ≥40-57% Decline in eGFR from Baseline
Time Frame: From the beginning of the simulation up to 10 years
Composite renal endpoint defined as time to end-stage kidney disease (ESKD), sustained decline in eGFR below 15 ml/min/1.73 m², or an irreversible decline ≥40-57% from baseline.
From the beginning of the simulation up to 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Non-fatal Acute Myocardial Infarction
Time Frame: From the beginning of the simulation up to 10 years
Monitoring of non-fatal acute myocardial infarction events as an exploratory atherothrombotic outcome.
From the beginning of the simulation up to 10 years
Number of Participants with Non-fatal Ischemic Stroke
Time Frame: From the beginning of the simulation up to 10 years
Monitoring of non-fatal ischemic stroke events as an exploratory atherothrombotic outcome.
From the beginning of the simulation up to 10 years
Annual Rate of Change in Estimated Glomerular Filtration Rate (eGFR) (ml/min/1.73 m²/year)
Time Frame: From the beginning of the simulation up to 10 years
Determination of the annual eGFR slope, separating the acute phase of the initial dip from chronic stabilization.
From the beginning of the simulation up to 10 years
Proportion of Participants with Transition Between Albuminuria Stages (Normo-, Micro-, Macroalbuminuria)
Time Frame: From the beginning of the simulation up to 10 years
Analysis of albuminuria stage transition, including regression or progression rates among normo-, micro-, and macroalbuminuria compartments.
From the beginning of the simulation up to 10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change from Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) (%)
Time Frame: Baseline to Month 6 and Month 12 and up to 10 years
Relative variation in UACR measured at 6 and 12 months of treatment.
Baseline to Month 6 and Month 12 and up to 10 years
Change from Baseline in NT-proBNP Levels (pg/mL)
Time Frame: From the beginning of the simulation up to 10 years
Simulated trajectory of NT-proBNP levels over time.
From the beginning of the simulation up to 10 years
Change from Baseline in CA-125 Levels (U/mL)
Time Frame: From the beginning of the simulation up to 10 years
Simulated trajectory of CA-125 levels over time.
From the beginning of the simulation up to 10 years
Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) to Assess Initial Dip and Long-term Preservation (ml/min/1.73 m²)
Time Frame: From the beginning of the simulation up to 10 years
Characterization of the initial hemodynamic eGFR dip induced by SGLT2i cotransport and quantification of long-term glomerular filtration preservation.
From the beginning of the simulation up to 10 years
Change from Baseline in Systolic Blood Pressure (mmHg)
Time Frame: From the beginning of the simulation up to 10 years
Continuous changes in systolic blood pressure during the study period.
From the beginning of the simulation up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aeterna Medical Solutions SL

Collaborators

Bayer Hispania, S.L

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

July 6, 2026

First Submitted That Met QC Criteria

July 17, 2026

First Posted (Actual)

July 22, 2026

Study Record Updates

Last Update Posted (Actual)

July 22, 2026

Last Update Submitted That Met QC Criteria

July 17, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HF_CKD_T2D001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Because all participants will be virtual

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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