Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)
10 de agosto de 2026 atualizado por: 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.
Visão geral do estudo
Status
Recrutamento
Descrição detalhada
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.
Tipo de estudo
Observacional
Inscrição (Estimado)
70
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Contato de estudo
- Nome: Luigi Colarusso, MD, PhD Candidate
- Número de telefone: +390902212341
- E-mail: luigi.colarusso@polime.it
Locais de estudo
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Sicily
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Messina, Sicily, Itália, 98124
- Recrutamento
- AOU Policlinico G. Martino, UOC Cardiologia con UTIC
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Contato:
- Luigi Colarusso, MD, PhD Candidate
- Número de telefone: +390902212341
- E-mail: luigi.colarusso@polime.it
-
Subinvestigador:
- Roberto Licordari, MD, PhD
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Investigador principal:
- Luigi Colarusso, MD, PhD Candidate
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Não
Método de amostragem
Amostra Não Probabilística
População do estudo
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.
Descrição
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.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
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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.
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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.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Liver Stiffness Measured by Transient Elastography (FibroScan)
Prazo: Baseline, 6 Months, 12 Months
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Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
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Baseline, 6 Months, 12 Months
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Controlled Attenuation Parameter (CAP) Measured by FibroScan
Prazo: Baseline, 6 months, 12 months
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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.
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Baseline, 6 months, 12 months
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Serum Aspartate Aminotransferase (AST/GOT)
Prazo: Baseline, 6 months, 12 months
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Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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Serum Alanine Aminotransferase (ALT/GPT)
Prazo: baseline, 6 months, 12 months
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Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Gamma-Glutamyl Transferase (GGT)
Prazo: baseline, 6 months, 12 months
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Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Alkaline Phosphatase (ALP)
Prazo: baseline, 6 months, 12 months
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Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Bile Acids
Prazo: baseline, 6 months, 12 months
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Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Total Bilirubin (mg/dL)
Prazo: baseline, 6 months, 12 months
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Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Direct Bilirubin (mg/dL)
Prazo: baseline, 6 months, 12 months
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Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Albumin (g/dL)
Prazo: baseline, 6 months, 12 months
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Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Gamma Globulins (g/dL)
Prazo: baseline, 6 months, 12 months
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Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Immunoglobulin M (IgM) (g/L)
Prazo: baseline, 6 months, 12 months
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Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Ferritin (ng/mL)
Prazo: baseline, 6 months, 12 months
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Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Anti-Mitochondrial Antibodies
Prazo: baseline, 6 months, 12 months
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U/ml
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baseline, 6 months, 12 months
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Fibrosis-4 (FIB-4) Index
Prazo: baseline, 6 months, 12 months
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FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Portal Vein Diameter Assessed by Liver Ultrasound
Prazo: baseline, 6 months, 12 months
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Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Prazo: baseline, 6 months, 12 months
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Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Spleen Diameter Assessed by Ultrasound (mm)
Prazo: baseline, 6 months, 12 months
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Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Prothrombin Time (PT) (s)
Prazo: baseline, 6 months, 12 months
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Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Activated Partial Thromboplastin Time (aPTT) (s)
Prazo: baseline, 6 months, 12 months
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Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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International Normalized Ratio (INR)
Prazo: baseline, 6 months, 12 months
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International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasma Fibrinogen
Prazo: baseline, 6 months, 12 months
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Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Fibrin/Fibrinogen Degradation Products
Prazo: Baseline, 6 months, 12 months
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Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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D-Dimer
Prazo: baseline, 6 months, 12 months
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D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Alpha-2-Antiplasmin
Prazo: baseline, 6 months, 12 months
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Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Antithrombin
Prazo: baseline, 6 months, 12 months
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Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasminogen
Prazo: baseline, 6 months, 12 months
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Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Thrombin-Antithrombin Complex
Prazo: baseline, 6 months, 12 months
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Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasmin-Alpha-2-Antiplasmin Complex
Prazo: baseline, 6 months, 12 months
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Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Prothrombin Fragment 1+2
Prazo: baseline, 6 months, 12 months
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Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Coagulation Factor X
Prazo: baseline, 6 months, 12 months
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Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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von Willebrand Factor Antigen
Prazo: baseline, 6 months, 12 months
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von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasminogen Activator Inhibitor-1 (PAI-1)
Prazo: baseline, 6 months, 12 months
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Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Prazo: Baseline
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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.
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Baseline
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Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)
Prazo: Baseline
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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.
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Baseline
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Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)
Prazo: Baseline
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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.
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Baseline
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Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)
Prazo: Baseline
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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.
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Baseline
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Change in Liver Stiffness During Disease-Modifying Treatment
Prazo: Baseline, 6±1 months, and 12±1 months
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Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.
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Baseline, 6±1 months, and 12±1 months
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Change in Controlled Attenuation Parameter During Disease-Modifying Treatment
Prazo: Baseline, 6±1 months, and 12±1 months
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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.
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Baseline, 6±1 months, and 12±1 months
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Prazo: 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
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Correlation Between FIB-4 Index and Prothrombin Fragment 1+2
Prazo: Baseline
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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
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Correlation Between Liver Stiffness and Fibrinogen
Prazo: Baseline
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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
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Cadeira de estudo: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
- Investigador principal: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
30 de janeiro de 2026
Conclusão Primária (Estimado)
1 de janeiro de 2028
Conclusão do estudo (Estimado)
1 de janeiro de 2028
Datas de inscrição no estudo
Enviado pela primeira vez
12 de junho de 2026
Enviado pela primeira vez que atendeu aos critérios de CQ
10 de agosto de 2026
Primeira postagem (Real)
14 de agosto de 2026
Atualizações de registro de estudo
Última Atualização Postada (Real)
14 de agosto de 2026
Última atualização enviada que atendeu aos critérios de controle de qualidade
10 de agosto de 2026
Última verificação
1 de junho de 2026
Mais Informações
Termos relacionados a este estudo
Palavras-chave
- Insuficiência cardíaca
- Hemostasia
- Biomarcadores
- Ecocardiografia
- Disfunção Hepática
- ATTR
- Fibroscan
- Amiloidose Transtirretina
- Amiloidose Cardíaca
- Tafamidis
- Rigidez do Fígado
- Acoramidis
- Distúrbio de Coagulação
- Estadiamento da Doença
- ATTR-CA
- Hepatic Congestion
- Cardiohepatic Syndrome
- Wild-Type ATTR
- Hereditary ATTR
Termos MeSH relevantes adicionais
- Doenças do Sistema Nervoso
- Doenças Vasculares
- Doenças cardiovasculares
- Doenças cardíacas
- Doenças Neuromusculares
- Metabolismo, Erros Inatos
- Doenças Genéticas, Congênitas
- Doenças Metabólicas
- Doenças do Sistema Nervoso Periférico
- Doenças do aparelho digestivo
- Doenças Hematológicas
- Doenças Neurodegenerativas
- Distúrbios Heredodegenerativos, Sistema Nervoso
- Distúrbios hemorrágicos
- Deficiências de Proteostase
- Neuropatias Amilóides
- Amiloidose Familiar
- Amiloidose
- Doenças e Anormalidades Congênitas, Hereditárias e Neonatais
- Doenças Nutricionais e Metabólicas
- Doenças hemic e linfáticas
- Insuficiência cardíaca
- Doenças do Fígado
- Cardiomiopatias
- Distúrbios hemostáticos
- Neuropatias Amilóides Familiares
- Amiloidose Hereditária Relacionada à Transtirretina
Outros números de identificação do estudo
- CEL Messina Prot. 28-25
- Delibera n. 63/2026 (Outro identificador: AOU Policlinico G. Martino)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
INDECISO
Descrição do plano IPD
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.
Informações sobre medicamentos e dispositivos, documentos de estudo
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Não
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
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