Cardiorenal Syndrome: Characteristics and Prognostic Impact in Advanced Heart Failure (CARAVEL)
Advanced heart failure (AHF) represents the end stage of chronic heart failure with reduced ejection fraction and affects up to 10% of patients with heart failure. These patients have refractory disease despite optimal guideline-directed medical therapy, and their management is discussed within a multidisciplinary "Heart Team".
Renal dysfunction is highly prevalent in this population. The coexistence of cardiac and renal dysfunction has been classified under the entity of cardiorenal syndrome. Impaired renal function is an independent predictor of adverse cardiovascular and renal outcomes, including death, heart failure decompensation, worsening renal function, and the need for renal replacement therapy. However, patients with AHF remain a particularly complex population, and the lack of longitudinal biological data and limited understanding of the dynamics of cardiorenal syndrome in relation to therapeutic interventions make prognosis assessment and individualized management challenging.
In addition, little is known about renal tubular function in AHF, despite its central role in hydro-electrolytic balance regulation. Biomarkers of tubular injury such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) have shown prognostic value in therapeutic studies, but their relationship with cardiac function and outcomes in advanced heart failure remains insufficiently characterized.
The primary objective of this study is to evaluate renal function parameters and their evolution over time through measurement of glomerular filtration rate (GFR) and assessment of tubular function in patients with advanced heart failure, and to investigate their association with major adverse cardiovascular events.
This is a prospective, single-center RIPH2 cohort study including 100 patients aged 18 to 75 years managed for advanced heart failure at the Louis Pradel Cardiovascular Hospital (Hospices Civils de Lyon, France). Patients will be followed according to standard care at 6, 12, 18, and 24 months. More comprehensive nephrological and cardiological evaluations will be performed at baseline, 12 months, and 24 months. Biobanking and quality-of-life questionnaires will also be conducted during these visits. Blood and urine samples will be collected at baseline and 12 months for NGAL et KIM-1 analysis. In addition, a subgroup of 50 consenting patients without contraindications will undergo multiparametric non-contrast renal MRI combined with tissue sodium quantification using 23Na MRI of the leg.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Nathan MEWTON, Pr
- Telefonnummer: +33 04 72 35 71 70
- E-post: nathan.mewton@chu-lyon.fr
Studiesteder
-
-
Rhone
-
Bron, Rhone, Frankrike, 69500
- Hospices Civils de Lyon
-
Ta kontakt med:
- Nathan MEWTON, Pr
- Telefonnummer: +33 04 72 35 71 70
- E-post: nathan.mewton@chu-lyon.fr
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Written informed consent signed by the patient,
- Age ≥ 18 years and ≤ 75 years,
Patient with advanced heart failure confirmed by criteria of severe cardiac dysfunction documented in a stable condition, with at least one of the following parameters at baseline:
- LVEF ≤ 35%,
- Elevated BNP or NT-proBNP levels (>200 ng/L for BNP and >1000 ng/L for NT-proBNP),
- NYHA class ≥ 3,
- At least one hospitalization for heart failure decompensation within the past 24 months,
- Optimized medical treatment for heart failure according to French/European cardiology guidelines at the maximum tolerated dose for >30 days.
Exclusion Criteria:
- Presence of severe extracardiac disease with a life expectancy < 1 year,
- Patient with end-stage renal disease (GFR <15 mL/min/1.73 m²) or on dialysis,
- History of heart, kidney, or other solid organ transplantation,
- Patient in cardiogenic shock,
- INTERMACS profile ≤ 3,
- Pregnant, parturient, or breastfeeding women*,
- Individuals deprived of liberty by judicial or administrative decision,
- Individuals under psychiatric care,
- Individuals admitted to a health or social institution for purposes other than research,
- Adults under legal protection (guardianship or curatorship),
- Individuals not affiliated with a social security system or equivalent coverage.
- Contraindication to multiparametric renal MRI combined with tissue sodium measurement using non-contrast 23Na MRI of the leg (including inability to undergo MRI as judged by the investigator).
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Annen
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Patients with cardiorenal syndrome
Patients with cardiorenal syndrome will be followed for 2 years in nephrology and cardiology according to standard of care.
|
Patients with cardiorenal syndrome will be followed for 2 years in nephrology and cardiology according to standard of care.
In addition, as part of the research, they will complete quality-of-life questionnaires and provide blood, urine, and stool samples for testing and biobanking.
An MRI will also be performed for patients participating in the ancillary study.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Occurrence of major cardiovascular events during the first 24 months
Tidsramme: At 12 and 24 months
|
The primary endpoint of this study is the occurrence of major cardiovascular events during the first 24 months: all-cause mortality, heart transplantation, implantation of a ventricular assist device, hospitalization for heart failure, or worsening ambulatory heart failure. The association between baseline renal function parameters (GFR, NGA, and KIM-1) and the occurrence of events during the first 24 months will be evaluated, as well as the association between renal function parameters at 12 months and the occurrence of major cardiovascular events between 12 and 24 months. |
At 12 and 24 months
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Blood and urinary levels of NGAL and KIM-1
Tidsramme: at baseline and at 12 months
|
Blood and urinary measurement of NGAL (neutrophil gelatinase-associated lipocalin) and KIM-1 (kidney injury molecule-1),
|
at baseline and at 12 months
|
|
Occurrence of major adverse renal events
Tidsramme: at baseline, 12 and 24 months
|
Occurrence of major adverse renal events during the first 24 months: persistent (>30 days) decline in glomerular filtration rate of >40%, initiation of renal replacement therapy, or death due to renal causes. The association between baseline GFR and the occurrence of adverse renal events during the first 24 months will be evaluated, as well as the association between changes in GFR between baseline and 12 months and the occurrence of adverse renal events between 12 and 24 months. Occurrence of major adverse renal events during the first 24 months: persistent (>30 days) decline in glomerular filtration rate of >40%, initiation of renal replacement therapy, or death due to renal causes. The association between baseline GFR and the occurrence of adverse renal events during the first 24 months will be evaluated, as well as the association between changes in GFR between baseline and 12 months and the occurrence of adverse renal events between 12 and 24 months. |
at baseline, 12 and 24 months
|
|
Occurrence of heart failure decompensation events
Tidsramme: at baseline, 12 and 24 months
|
Occurrence of heart failure decompensation events (hospitalization, ventricular assist device implantation, or outpatient worsening) during the first 24 months.
The association between specific biomarkers of renal tubular injury (serum and urinary NGAL and KIM-1) at baseline and heart failure decompensation events during the first 24 months will be analysed, as well as the association between changes in specific biomarkers of renal tubular injury between baseline and 12 months and the occurrence of heart failure decompensation events between 12 and 24 months.
|
at baseline, 12 and 24 months
|
|
Clinical data collected over a 24-month follow-up period
Tidsramme: over 24 months
|
Description of the study population over 24 months of follow-up (clinical, paraclinical, therapeutic characteristics, and serious adverse events),
|
over 24 months
|
|
Score of KCCQ questionnaire
Tidsramme: at baseline, and at 6, 12, 18, and 24 months
|
Each item of KCCQ questionnaire is scored on a 5-point Likert scale and transformed to a 0-100 scale, with higher scores indicating better health status.
|
at baseline, and at 6, 12, 18, and 24 months
|
|
Biomarkers identification
Tidsramme: At baseline, 12 months and 24 months
|
IBiomarkers identification in biological samples collected in the study biocollection.
|
At baseline, 12 months and 24 months
|
|
Multiparametric renal MRI
Tidsramme: at baseline and at 12 months
|
Multiparametric renal MRI (BOLD, diffusion, T1 and T2 mapping) in a subgroup of 50 voluntary patients (optional examination)
|
at baseline and at 12 months
|
|
Tissue sodium measurement
Tidsramme: at baseline and at 12 months.
|
Tissue sodium measurement using 23Na MRI of the leg in a subgroup of 50 voluntary patients (optional examination)
|
at baseline and at 12 months.
|
|
Score of Morisky self-questionnaire MMAS-4
Tidsramme: at baseline, and at 6, 12, 18, and 24 months,
|
Morisky self-questionnaire MMAS-4 is a generic patient-reported questionnaire used to assess medication adherence.
The scale consists of four items, each scored as 0 for "Yes" and 1 for "No".
The item scores are summed to yield a total score ranging from 0 to 4. Higher scores indicate better medication adherence.
|
at baseline, and at 6, 12, 18, and 24 months,
|
Samarbeidspartnere og etterforskere
Sponsor
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 69HCL20_0968
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .