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NCT Number: NCT07766135

Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis

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.

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Key information

Conditions

Transthyretin (TTR) Amyloid Cardiomyopathy Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis Amyloidosis, Familial Amyloidosis, Hereditary, Transthyretin-Related Cardiac Amyloidosis Cardiomyopathies Cardiovascular Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Heart Diseases Heart Failure Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hereditary Transthyretin Amyloidosis (ATTRv) Heredodegenerative Disorders, Nervous System Liver Diseases Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Peripheral Nervous System Diseases Proteostasis Deficiencies Vascular Diseases Wild-Type Transthyretin Cardiac Amyloidosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

AOU Policlinico G. Martino, UOC Cardiologia con UTIC

Messina, Sicily, 98124, Italy

Location status: Recruiting

Location contact

Luigi Colarusso, MD, PhD Candidate

CONTACT

[email protected]

+390902212341

Luigi Colarusso, MD, PhD Candidate

PRINCIPAL_INVESTIGATOR

Roberto Licordari, MD, PhD

SUB_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Liver Stiffness Measured by Transient Elastography (FibroScan)

    Time frame: Baseline, 6 Months, 12 Months

    Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.

  2. Controlled Attenuation Parameter (CAP) Measured by FibroScan

    Time frame: 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.

  3. Serum Aspartate Aminotransferase (AST/GOT)

    Time frame: Baseline, 6 months, 12 months

    Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  4. Serum Alanine Aminotransferase (ALT/GPT)

    Time frame: baseline, 6 months, 12 months

    Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  5. Serum Gamma-Glutamyl Transferase (GGT)

    Time frame: 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.

  6. Serum Alkaline Phosphatase (ALP)

    Time frame: baseline, 6 months, 12 months

    Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  7. Serum Bile Acids

    Time frame: baseline, 6 months, 12 months

    Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.

  8. Total Bilirubin (mg/dL)

    Time frame: baseline, 6 months, 12 months

    Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  9. Direct Bilirubin (mg/dL)

    Time frame: baseline, 6 months, 12 months

    Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  10. Serum Albumin (g/dL)

    Time frame: baseline, 6 months, 12 months

    Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  11. Serum Gamma Globulins (g/dL)

    Time frame: baseline, 6 months, 12 months

    Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  12. Serum Immunoglobulin M (IgM) (g/L)

    Time frame: baseline, 6 months, 12 months

    Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  13. Serum Ferritin (ng/mL)

    Time frame: baseline, 6 months, 12 months

    Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  14. Anti-Mitochondrial Antibodies

    Time frame: baseline, 6 months, 12 months

    U/ml

  15. Fibrosis-4 (FIB-4) Index

    Time frame: baseline, 6 months, 12 months

    FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.

  16. Portal Vein Diameter Assessed by Liver Ultrasound

    Time frame: baseline, 6 months, 12 months

    Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.

  17. Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)

    Time frame: baseline, 6 months, 12 months

    Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.

  18. Spleen Diameter Assessed by Ultrasound (mm)

    Time frame: baseline, 6 months, 12 months

    Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.

  19. Prothrombin Time (PT) (s)

    Time frame: baseline, 6 months, 12 months

    Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  20. Activated Partial Thromboplastin Time (aPTT) (s)

    Time frame: baseline, 6 months, 12 months

    Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  21. International Normalized Ratio (INR)

    Time frame: baseline, 6 months, 12 months

    International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  22. Plasma Fibrinogen

    Time frame: baseline, 6 months, 12 months

    Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  23. Fibrin/Fibrinogen Degradation Products

    Time frame: 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.

  24. D-Dimer

    Time frame: baseline, 6 months, 12 months

    D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  25. Alpha-2-Antiplasmin

    Time frame: 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.

  26. Antithrombin

    Time frame: baseline, 6 months, 12 months

    Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  27. Plasminogen

    Time frame: baseline, 6 months, 12 months

    Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  28. Thrombin-Antithrombin Complex

    Time frame: baseline, 6 months, 12 months

    Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  29. Plasmin-Alpha-2-Antiplasmin Complex

    Time frame: 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.

  30. Prothrombin Fragment 1+2

    Time frame: 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.

  31. Coagulation Factor X

    Time frame: baseline, 6 months, 12 months

    Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  32. von Willebrand Factor Antigen

    Time frame: 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.

  33. Plasminogen Activator Inhibitor-1 (PAI-1)

    Time frame: 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.

Secondary outcomes

  1. Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)

    Time frame: 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.

  2. Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)

    Time frame: 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.

  3. Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)

    Time frame: 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.

  4. Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)

    Time frame: 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.

  5. Change in Liver Stiffness During Disease-Modifying Treatment

    Time frame: 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.

  6. Change in Controlled Attenuation Parameter During Disease-Modifying Treatment

    Time frame: 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.

Other outcomes

  1. Correlation Between Liver Stiffness and Prothrombin Fragment 1+2

    Time frame: 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.

  2. Correlation Between FIB-4 Index and Prothrombin Fragment 1+2

    Time frame: 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.

  3. Correlation Between Liver Stiffness and Fibrinogen

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Luigi Colarusso, MD, PhD Candidate

CONTACT

[email protected]

+390902212341

Sponsors and collaborators

Lead sponsor

University of Messina

Other

Collaborators

  • Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Registry information

Official study title

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

Acronym: LICA2025

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Aug 14, 2026
Registry last updated
Aug 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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