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NCT Number: NCT06832371

Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia

This observational, multicenter, retrospective and prospective study aims to evaluate the effect of lomitapide treatment on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH).

HoFH is a rare genetic disorder characterized by extremely high levels of LDL cholesterol (LDL-C), leading to an increased risk of early cardiovascular diseases. Lomitapide is an approved medication that lowers LDL-C levels by inhibiting microsomal triglyceride transfer protein (MTP).

The study will collect data from patients who have been treated with lomitapide for at least 12 months and will compare the incidence of MACE during the first three years of treatment with the three years before treatment initiation. The study includes data collection from multiple lipid centers across Europe.

The primary objective is to assess the impact of lomitapide on MACE, while secondary objectives include evaluating changes in lipid profiles, liver function tests, and lipid-lowering treatments.

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Key information

Conditions

Homozygous Familial Hypercholesterolemia (HoFH) Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Cardiovascular Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dyslipidemia Dyslipidemias Genetic Diseases, Inborn Homozygous Familial Hypercholesterolemia Hypercholesterolemia Hyperlipidemias Hyperlipoproteinemia Type II Hyperlipoproteinemias Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Major Adverse Cardiovascular Events (MACE) Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHRU Lille - Centre Hospitalier Universitaire de Lille, Lille, France

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About this study

This is a multicenter, international, long-term observational study investigating the real-world impact of lomitapide on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH).

Study Design:

Observational, open-label, retrospective and prospective study Data will be collected from 30 lipid centers across Europe Patients will serve as their own control, with comparisons between pre-treatment (3 years before lomitapide) and post-treatment (first 3 years of lomitapide therapy) periods

Study Population:

Approximately 72 adult patients (≥18 years) diagnosed with HoFH Patients must have received lomitapide for at least 12 months Availability of 3 years of pre-treatment clinical records

Objectives:

Primary Objective: Evaluate the incidence of MACE before and after lomitapide treatment

Secondary Objectives: Assess changes in LDL-C, total cholesterol, liver function tests (ALT, AST, GGT), and lipid-lowering therapy usage (e.g., discontinuation of LDL apheresis, addition of PCSK9 inhibitors)

Endpoints:

Primary Endpoint: Change in MACE incidence over the 3-year treatment period

Secondary Endpoints: Changes in lipid levels, liver safety markers, and adherence to treatment protocols

Safety Considerations:

The study follows real-world clinical practice, with monitoring of adverse events, including liver-related safety concerns associated with lomitapide

Data will be collected in an electronic Case Report Form (eCRF) and analyzed following Good Clinical Practice (GCP) guidelines

This study aims to generate real-world evidence on the cardiovascular impact of lomitapide in HoFH patients, addressing an unmet clinical need for data on long-term outcomes.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Adult patients (age ≥18 years)
  • Clinical or genetic diagnosis of HoFH
  • Treated with lomitapide at any dosage
  • On treatment with lomitapide for at least 12 months at the time of enrollment
  • Availability of 3 years of medical records prior to lomitapide treatment to confirm MACE
  • Giving written informed consent

Exclusion criteria

  • Patients who were prescribed lomitapide outside of the marketing authorization or in contraindicated patients
  • Patients receiving lomitapide in clinical trials
  • Patients receiving an investigational agent, defined as any drug or biologic agent other than lomitapide that has not received Market Authorization in the country of participation, at the time of enrolment

Treatment and study plan

Primary outcomes

  1. Incidence of Major Adverse Cardiovascular Events (MACE) Before and After Lomitapide Treatment

    Time frame: 3 years before treatment vs. 3 years during treatment

    This measure will assess the incidence of MACE (including myocardial infarction, stroke, cardiovascular death, and hospitalization due to unstable angina) during the first three years of lomitapide treatment compared to the three years prior to treatment initiation.

    Unit of Measure: Number of events per 100 patient-years.

Secondary outcomes

  1. Change in LDL-Cholesterol Levels

    Time frame: Baseline, 1 year, 2 years, 3 years

    This measure will evaluate changes in LDL-C levels. Unit of Measure: mg/dL.

  2. Change in Total Cholesterol, Triglycerides, and HDL-Cholesterol

    Time frame: Baseline, 1 year, 2 years, 3 years

    Assess changes in total cholesterol, triglycerides, and HDL-C at 1, 2, and 3 years after lomitapide treatment initiation.

    Unit of Measure: mg/dL.

  3. Change in Triglyceride Levels

    Time frame: Baseline, 1 year, 2 years, 3 years.

    This measure will evaluate changes in triglyceride levels. Unit of Measure: mg/dL.

  4. Change in HDL-Cholesterol Levels

    Time frame: Baseline, 1 year, 2 years, 3 years

    This measure will evaluate changes in HDL-C levels. Unit of Measure: mg/dL.

  5. Liver Safety Profile - ALT Levels

    Time frame: Baseline, 1 year, 2 years, 3 years.

    This measure will evaluate changes in alanine aminotransferase (ALT) levels. Unit of Measure: U/L.

  6. Liver Safety Profile - AST Levels

    Time frame: Baseline, 1 year, 2 years, 3 years.

    This measure will evaluate changes in aspartate aminotransferase (AST) levels. Unit of Measure: U/L.

  7. Liver Safety Profile - GGT Levels

    Time frame: Baseline, 1 year, 2 years, 3 years.

    This measure will evaluate changes in gamma-glutamyl transferase (GGT) levels. Unit of Measure: U/L.

  8. Lipid-Lowering Therapy Modifications

    Time frame: Baseline, 1 year, 2 years, 3 years.

    This measure will track changes in lipid-lowering therapies, for example the discontinuation of LDL apheresis or the introduction of evinacumab, as described in the study protocol.

    Unit of Measure: Number of patients with therapy modifications.

Other outcomes

  1. Biomarkers of Liver and Vascular Damage

    Time frame: Baseline and after 3 years of lomitapide treatment.

    This measure will evaluate biomarkers of liver and vascular damage, including FIB4, apolipoprotein B, lipoprotein(a), cytokeratin 18 fragment (CK-18F), hematology, and other relevant markers.

    Unit of Measure: Laboratory values in mg/dL or U/L, as applicable.

  2. Presence and Severity of Hepatic Steatosis

    Time frame: After 3 years of lomitapide treatment.

    This measure will assess the presence and severity of hepatic steatosis using liver ultrasound or MRI. Severity will be graded as absent, mild, moderate, or severe.

    Unit of Measure: Qualitative assessment (absent, mild, moderate, severe).

  3. Liver Elastography Parameters

    Time frame: After 3 years of lomitapide treatment.

    This measure will evaluate liver elastography parameters using fibroscan or other methods. Measurements will include liver stiffness (kPa) and controlled attenuation parameter (CAP) values.

    Unit of Measure: kPa (kilopascal) and CAP (dB/m).

  4. Dietary Records

    Time frame: After 3 years of lomitapide treatment.

    This measure will evaluate dietary patterns using a food frequency questionnaire (FFQ) for patients participating in the prospective phase of the study.

    Unit of Measure: Responses to FFQ (categorical and quantitative data).

  5. Adherence to Lipid-Lowering Medications

    Time frame: After 3 years of lomitapide treatment.

    This measure will evaluate adherence to lipid-lowering medications, including lomitapide, using a Medication Adherence Scale for patients participating in the prospective phase.

    Unit of Measure: Medication Adherence Scale scores.

Sponsors and collaborators

Lead sponsor

Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)

Other

Collaborators

  • Amryt Pharmaceuticals DAC
  • CMV-Stat S.r.l.
  • Clinical Trial Consulting

Registry information

Official study title

Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia: A Multicenter, Retrospective and Prospective Observational Study

Acronym: LILITH

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Feb 18, 2025
Registry last updated
Feb 20, 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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