Evaluation of the Risk of Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes Mellitus
torstai 10. syyskuuta 2026 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Tila
Valmis
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Havainnollistava
Ilmoittautuminen (Todellinen)
100000
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Madrid, Espanja
- Hospital Clinico San Carlos
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Lapsi
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Ei
Näytteenottomenetelmä
Ei-todennäköisyysnäyte
Tutkimusväestö
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.
Kuvaus
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.
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
Kohortit ja interventiot
Ryhmä/Kohortti |
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Reference Monotherapy
Finerenone
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Early Combo Strategy
Concomitant combination of finerenone and empagliflozin
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Time to First Occurrence of Incident Heart Failure, Heart Failure Hospitalization, or Cardiovascular Death
Aikaikkuna: From the beginning of the simulation up to 10 years
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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.
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From the beginning of the simulation up to 10 years
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Time to Onset of End-Stage Kidney Disease, Sustained eGFR <15 ml/min/1.73 m², or ≥40-57% Decline in eGFR from Baseline
Aikaikkuna: 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.
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From the beginning of the simulation up to 10 years
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Number of Participants with Non-fatal Acute Myocardial Infarction
Aikaikkuna: From the beginning of the simulation up to 10 years
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Monitoring of non-fatal acute myocardial infarction events as an exploratory atherothrombotic outcome.
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From the beginning of the simulation up to 10 years
|
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Number of Participants with Non-fatal Ischemic Stroke
Aikaikkuna: From the beginning of the simulation up to 10 years
|
Monitoring of non-fatal ischemic stroke events as an exploratory atherothrombotic outcome.
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From the beginning of the simulation up to 10 years
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Annual Rate of Change in Estimated Glomerular Filtration Rate (eGFR) (ml/min/1.73 m²/year)
Aikaikkuna: From the beginning of the simulation up to 10 years
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Determination of the annual eGFR slope, separating the acute phase of the initial dip from chronic stabilization.
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From the beginning of the simulation up to 10 years
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Proportion of Participants with Transition Between Albuminuria Stages (Normo-, Micro-, Macroalbuminuria)
Aikaikkuna: From the beginning of the simulation up to 10 years
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Analysis of albuminuria stage transition, including regression or progression rates among normo-, micro-, and macroalbuminuria compartments.
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From the beginning of the simulation up to 10 years
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Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Percent Change from Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) (%)
Aikaikkuna: Baseline to Month 6 and Month 12 and up to 10 years
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Relative variation in UACR measured at 6 and 12 months of treatment.
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Baseline to Month 6 and Month 12 and up to 10 years
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Change from Baseline in NT-proBNP Levels (pg/mL)
Aikaikkuna: From the beginning of the simulation up to 10 years
|
Simulated trajectory of NT-proBNP levels over time.
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From the beginning of the simulation up to 10 years
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Change from Baseline in CA-125 Levels (U/mL)
Aikaikkuna: From the beginning of the simulation up to 10 years
|
Simulated trajectory of CA-125 levels over time.
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From the beginning of the simulation up to 10 years
|
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Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) to Assess Initial Dip and Long-term Preservation (ml/min/1.73 m²)
Aikaikkuna: 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.
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From the beginning of the simulation up to 10 years
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Change from Baseline in Systolic Blood Pressure (mmHg)
Aikaikkuna: From the beginning of the simulation up to 10 years
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Continuous changes in systolic blood pressure during the study period.
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From the beginning of the simulation up to 10 years
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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Yhteistyökumppanit
Julkaisuja ja hyödyllisiä linkkejä
Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.
Yleiset julkaisut
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Opintojen ennätyspäivät
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Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Urogenitaaliset sairaudet
- Endokriinisen järjestelmän sairaudet
- Patologiset prosessit
- Miesten urogenitaaliset sairaudet
- Munuaissairaudet
- Urologiset sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet ja raskauden komplikaatiot
- Krooninen sairaus
- Sairauden ominaisuudet
- Metaboliset sairaudet
- Glukoosiaineenvaihduntahäiriöt
- Diabetes mellitus
- Munuaisten vajaatoiminta
- Patologiset tilat, merkit ja oireet
- Ravitsemukselliset ja aineenvaihduntataudit
- Diabetes mellitus, tyyppi 2
- Munuaisten vajaatoiminta, krooninen
Muut tutkimustunnusnumerot
- HF_CKD_T2D001
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
EI
IPD-suunnitelman kuvaus
Because all participants will be virtual
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .