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Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)

10. august 2026 oppdatert av: Gianluca Di Bella, University of Messina

Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (ATTR-CA): New Horizons in Disease Staging and Follow-Up

Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by the deposition of misfolded transthyretin protein within the myocardium. Current disease staging and follow-up strategies mainly rely on cardiac biomarkers and renal function; however, the systemic nature of ATTR suggests that additional organ involvement may provide valuable prognostic information.

The purpose of this prospective observational study is to investigate liver dysfunction and coagulation abnormalities in patients with wild-type or hereditary ATTR-CA and to evaluate their potential role as novel markers of disease severity and progression. Patients with ATTR-CA will be compared with an age-matched control population with non-amyloid hypertrophic cardiomyopathy.

Clinical, laboratory, echocardiographic, hepatic ultrasound, liver stiffness, and coagulation parameters will be assessed at baseline and during follow-up. The study will also evaluate changes in these parameters after 6 and 12 months of treatment with tafamidis.

The results may improve the understanding of cardio-hepatic interactions in ATTR-CA and identify new tools for disease staging and longitudinal monitoring.

Studieoversikt

Status

Rekruttering

Forhold

Detaljert beskrivelse

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure and left ventricular hypertrophy in older adults. Although several prognostic models have been developed for ATTR-CA, most currently available staging systems are based primarily on cardiac biomarkers and renal function. These approaches may not fully capture the systemic nature of the disease.

Emerging evidence suggests that liver dysfunction and coagulation abnormalities may represent underexplored manifestations of ATTR-CA. Liver involvement may result from direct amyloid deposition, chronic venous congestion related to heart failure, or a combination of both mechanisms. Similarly, alterations in coagulation pathways may reflect hepatic dysfunction and systemic disease burden.

LICA2025 is a single-center, prospective, observational study designed to evaluate biochemical and instrumental markers of liver function and coagulation in patients with wild-type or hereditary ATTR-CA followed at the University Hospital G. Martino of Messina, Italy. A control population with non-amyloid hypertrophic cardiomyopathy will be enrolled for comparison.

The primary objective is to compare liver and coagulation parameters between ATTR-CA patients and controls. Secondary objectives include evaluating the relationship between hepatic/coagulation abnormalities and cardiac disease severity, assessing changes after 6±1 and 12±1 months of tafamidis therapy, and exploring potential interactions between liver dysfunction and coagulation disturbances.

Participants will undergo clinical evaluation, laboratory testing, electrocardiography, transthoracic echocardiography, hepatic ultrasound, liver elastography (FibroScan), and coagulation assessment according to the study protocol. Follow-up evaluations will be performed at baseline, 6 months, and 12 months.

The study aims to identify novel biomarkers and imaging parameters that may improve disease staging, risk stratification, and longitudinal monitoring in transthyretin cardiac amyloidosis.

Studietype

Observasjonsmessig

Registrering (Antatt)

70

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Italia
    • Sicily
      • Messina, Sicily, Italia, 98124
        • Rekruttering
        • AOU Policlinico G. Martino, UOC Cardiologia con UTIC
        • Ta kontakt med:
        • Underetterforsker:
          • Roberto Licordari, MD, PhD
        • Hovedetterforsker:
          • Luigi Colarusso, MD, PhD Candidate

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

Adult patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) followed at the University Hospital G. Martino, Messina, Italy, and an age-matched control population with non-amyloid hypertrophic phenotype cardiomyopathy.

Beskrivelse

Inclusion Criteria:

  • Written informed consent obtained prior to study participation.
  • Diagnosis of wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) according to current European recommendations.
  • Ability to comply with study procedures and follow-up visits.

Exclusion Criteria:

  • Age younger than 18 years.
  • Severe liver dysfunction due to causes other than amyloidosis.
  • Inability to comply with study procedures because of language barriers, cognitive impairment, or severe psychiatric disorders.
  • Comorbidities associated with life expectancy less than 12 months.
  • Active alcohol or substance abuse.
  • For coagulation analyses: congenital coagulation disorders, thrombotic disorders, active malignancy, or sepsis.
  • Pregnancy or breastfeeding.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Kohorter og intervensjoner

Gruppe / Kohort
ATTR-CA Patients
Patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) diagnosed according to current European recommendations and followed at the University Hospital G. Martino, Messina. Participants will undergo clinical, laboratory, echocardiographic, hepatic ultrasound, liver elastography, and coagulation assessments at baseline and during follow-up.
Hypertrophic Phenotype Controls
Age-matched patients with non-amyloid hypertrophic phenotype cardiomyopathy serving as a control population. Participants will undergo the same clinical, laboratory, echocardiographic, hepatic, and coagulation evaluations as the ATTR-CA group.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Liver Stiffness Measured by Transient Elastography (FibroScan)
Tidsramme: Baseline, 6 Months, 12 Months
Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
Baseline, 6 Months, 12 Months
Controlled Attenuation Parameter (CAP) Measured by FibroScan
Tidsramme: Baseline, 6 months, 12 months
Controlled attenuation parameter (CAP) measured by FibroScan as an instrumental measure of hepatic steatosis, expressed in decibels per meter (dB/m), compared between patients with ATTR-CA and controls.
Baseline, 6 months, 12 months
Serum Aspartate Aminotransferase (AST/GOT)
Tidsramme: Baseline, 6 months, 12 months
Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Baseline, 6 months, 12 months
Serum Alanine Aminotransferase (ALT/GPT)
Tidsramme: baseline, 6 months, 12 months
Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Gamma-Glutamyl Transferase (GGT)
Tidsramme: baseline, 6 months, 12 months
Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Alkaline Phosphatase (ALP)
Tidsramme: baseline, 6 months, 12 months
Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Bile Acids
Tidsramme: baseline, 6 months, 12 months
Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Total Bilirubin (mg/dL)
Tidsramme: baseline, 6 months, 12 months
Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Direct Bilirubin (mg/dL)
Tidsramme: baseline, 6 months, 12 months
Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Albumin (g/dL)
Tidsramme: baseline, 6 months, 12 months
Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Gamma Globulins (g/dL)
Tidsramme: baseline, 6 months, 12 months
Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Immunoglobulin M (IgM) (g/L)
Tidsramme: baseline, 6 months, 12 months
Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Ferritin (ng/mL)
Tidsramme: baseline, 6 months, 12 months
Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Anti-Mitochondrial Antibodies
Tidsramme: baseline, 6 months, 12 months
U/ml
baseline, 6 months, 12 months
Fibrosis-4 (FIB-4) Index
Tidsramme: baseline, 6 months, 12 months
FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Portal Vein Diameter Assessed by Liver Ultrasound
Tidsramme: baseline, 6 months, 12 months
Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Tidsramme: baseline, 6 months, 12 months
Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Spleen Diameter Assessed by Ultrasound (mm)
Tidsramme: baseline, 6 months, 12 months
Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Prothrombin Time (PT) (s)
Tidsramme: baseline, 6 months, 12 months
Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Activated Partial Thromboplastin Time (aPTT) (s)
Tidsramme: baseline, 6 months, 12 months
Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
International Normalized Ratio (INR)
Tidsramme: baseline, 6 months, 12 months
International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasma Fibrinogen
Tidsramme: baseline, 6 months, 12 months
Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Fibrin/Fibrinogen Degradation Products
Tidsramme: Baseline, 6 months, 12 months
Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Baseline, 6 months, 12 months
D-Dimer
Tidsramme: baseline, 6 months, 12 months
D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Alpha-2-Antiplasmin
Tidsramme: baseline, 6 months, 12 months
Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Antithrombin
Tidsramme: baseline, 6 months, 12 months
Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasminogen
Tidsramme: baseline, 6 months, 12 months
Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Thrombin-Antithrombin Complex
Tidsramme: baseline, 6 months, 12 months
Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex
Tidsramme: baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Prothrombin Fragment 1+2
Tidsramme: baseline, 6 months, 12 months
Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Coagulation Factor X
Tidsramme: baseline, 6 months, 12 months
Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
von Willebrand Factor Antigen
Tidsramme: baseline, 6 months, 12 months
von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 (PAI-1)
Tidsramme: baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Tidsramme: Baseline
Correlation between liver stiffness measured by FibroScan (kPa) and plasma NT-proBNP concentration (ng/L) in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline
Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)
Tidsramme: Baseline
Correlation between liver stiffness measured by FibroScan (kPa) and interventricular septal thickness expressed in mm measured by transthoracic echocardiography in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline
Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)
Tidsramme: Baseline
Correlation between liver stiffness measured by FibroScan (kPa) and Global Longitudinal Strain (expressed in %) measured by transthoracic echocardiography in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline
Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)
Tidsramme: Baseline
Correlation between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L) measured by standard laboratory testing in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline
Change in Liver Stiffness During Disease-Modifying Treatment
Tidsramme: Baseline, 6±1 months, and 12±1 months
Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.
Baseline, 6±1 months, and 12±1 months
Change in Controlled Attenuation Parameter During Disease-Modifying Treatment
Tidsramme: Baseline, 6±1 months, and 12±1 months
Change in controlled attenuation parameter (CAP) measured by FibroScan and expressed in dB/m from baseline to 6±1 months and 12±1 months after treatment initiation.
Baseline, 6±1 months, and 12±1 months

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Tidsramme: Baseline
Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline
Correlation Between FIB-4 Index and Prothrombin Fragment 1+2
Tidsramme: Baseline
Correlation between FIB-4 and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline
Correlation Between Liver Stiffness and Fibrinogen
Tidsramme: Baseline
Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma fibrinogen concentration in patients with ATTR-CA. Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
Baseline

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University of Messina

Samarbeidspartnere

Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Etterforskere

  • Studiestol: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
  • Hovedetterforsker: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

30. januar 2026

Primær fullføring (Antatt)

1. januar 2028

Studiet fullført (Antatt)

1. januar 2028

Datoer for studieregistrering

Først innsendt

12. juni 2026

Først innsendt som oppfylte QC-kriteriene

10. august 2026

Først lagt ut (Faktiske)

14. august 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

14. august 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

10. august 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CEL Messina Prot. 28-25
  • Delibera n. 63/2026 (Annen identifikator: AOU Policlinico G. Martino)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

UBESLUTTE

IPD-planbeskrivelse

The decision regarding IPD sharing has not yet been finalized. Any future data sharing will be considered in accordance with applicable ethical approvals, participant consent, institutional policies, and data protection regulations.

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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. .

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