Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)
10 de agosto de 2026 actualizado 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.
Descripción general del estudio
Estado
Reclutamiento
Descripción detallada
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 estudio
De observación
Inscripción (Estimado)
70
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Luigi Colarusso, MD, PhD Candidate
- Número de teléfono: +390902212341
- Correo electrónico: luigi.colarusso@polime.it
Ubicaciones de estudio
-
-
Sicily
-
Messina, Sicily, Italia, 98124
- Reclutamiento
- AOU Policlinico G. Martino, UOC Cardiologia con UTIC
-
Contacto:
- Luigi Colarusso, MD, PhD Candidate
- Número de teléfono: +390902212341
- Correo electrónico: luigi.colarusso@polime.it
-
Sub-Investigador:
- Roberto Licordari, MD, PhD
-
Investigador principal:
- Luigi Colarusso, MD, PhD Candidate
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Método de muestreo
Muestra no probabilística
Población de estudio
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.
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
|---|
|
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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Liver Stiffness Measured by Transient Elastography (FibroScan)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: baseline, 6 months, 12 months
|
U/ml
|
baseline, 6 months, 12 months
|
|
Fibrosis-4 (FIB-4) Index
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Periodo de tiempo: 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)
Periodo de tiempo: 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 %)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Silla de estudio: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
- Investigador principal: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
30 de enero de 2026
Finalización primaria (Estimado)
1 de enero de 2028
Finalización del estudio (Estimado)
1 de enero de 2028
Fechas de registro del estudio
Enviado por primera vez
12 de junio de 2026
Primero enviado que cumplió con los criterios de control de calidad
10 de agosto de 2026
Publicado por primera vez (Actual)
14 de agosto de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
14 de agosto de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
10 de agosto de 2026
Última verificación
1 de junio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
- Insuficiencia cardiaca
- Hemostasia
- Biomarcadores
- Ecocardiografía
- Disfunción hepática
- ATTR
- Fibroscan
- Amiloidosis por transtiretina
- Amiloidosis cardíaca
- Tafamidis
- Rigidez del hígado
- Acoramidis
- Trastorno de coagulación
- Estadificación de la enfermedad
- ATTR-CA
- Hepatic Congestion
- Cardiohepatic Syndrome
- Wild-Type ATTR
- Hereditary ATTR
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Nervioso
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Enfermedades cardíacas
- Enfermedades Neuromusculares
- Metabolismo, errores congénitos
- Enfermedades Genéticas Congénitas
- Enfermedades metabólicas
- Enfermedades del Sistema Nervioso Periférico
- Enfermedades del Sistema Digestivo
- Enfermedades hematológicas
- Enfermedades neurodegenerativas
- Trastornos Heredodegenerativos, Sistema Nervioso
- Trastornos hemorrágicos
- Deficiencias de proteostasis
- Neuropatías amiloides
- Amiloidosis Familiar
- Amilosis
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Enfermedades Nutricionales y Metabólicas
- Enfermedades hemic y linfáticas
- Insuficiencia cardiaca
- Enfermedades del HIGADO
- Miocardiopatías
- Trastornos hemostáticos
- Neuropatías Amiloide, Familiar
- Amiloidosis Hereditaria Relacionada con Transtiretina
Otros números de identificación del estudio
- CEL Messina Prot. 28-25
- Delibera n. 63/2026 (Otro identificador: AOU Policlinico G. Martino)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
INDECISO
Descripción del plan 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.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .