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

NCT06832371 | Active Not Recruiting DMC

• 1 other identifier: LILITH
• Study Type: observational
• Target: 73
• Locations: 5 countries
• Sites: 30

Brief Summary

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.

Conditions

Major Adverse Cardiovascular Events (MACE); Homozygous Familial Hypercholesterolemia (HoFH); Dyslipidemia

Keywords

Lomitapide; Hypercholesterolemia; Cardiovascular Disease; LDL Cholesterol; Lipid-Lowering Therapy; Lipid Metabolism Disorders; Atherosclerosis; Rare Genetic Disorders

Outcome Measures

Primary Outcomes (1)

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

  3 years before treatment vs. 3 years during treatment

Secondary Outcomes (8)

• Change in LDL-Cholesterol Levels

  Baseline, 1 year, 2 years, 3 years

• Change in Total Cholesterol, Triglycerides, and HDL-Cholesterol

  Baseline, 1 year, 2 years, 3 years

• Change in Triglyceride Levels

  Baseline, 1 year, 2 years, 3 years.

• Change in HDL-Cholesterol Levels

  Baseline, 1 year, 2 years, 3 years

• Liver Safety Profile - ALT Levels

  Baseline, 1 year, 2 years, 3 years.

Other Outcomes (5)

• Biomarkers of Liver and Vascular Damage

  Baseline and after 3 years of lomitapide treatment.

• Presence and Severity of Hepatic Steatosis

  After 3 years of lomitapide treatment.

• Liver Elastography Parameters

  After 3 years of lomitapide treatment.

Study Arms (1)

HoFH Patients Treated with Lomitapide

This cohort consists of adult patients (≥18 years) diagnosed with Homozygous Familial Hypercholesterolemia (HoFH) who have been treated with lomitapide for at least 12 months. The study will retrospectively analyze the incidence of Major Adverse Cardiovascular Events (MACE) in the three years before lomitapide treatment, and prospectively track MACE incidence during the first three years of lomitapide therapy.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a clinical or genetic diagnosis of homozygous familial hypercholesterolemia (HoFH) who have been treated with lomitapide for at least 12 months.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CMV-Stat S.r.l.: collaborator
• Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi): lead
• Amryt Pharmaceuticals DAC: collaborator
• Clinical Trial Consulting: collaborator

Study Sites (30)

CHRU Lille - Centre Hospitalier Universitaire de Lille

Lille, France

Location

Centre Hospitalier Universitaire de Lyon (CHU Lyon)

Lyon, France

Location

Hôpital de la Conception - Assistance Publique Hôpitaux de Marseille (AP-HM)

Marseille, France

Location

Hôpital La Pitié Salpêtrière - Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix"

Paris, France

Location

Strasbourg University Hospital (CHU Strasbourg)

Strasbourg, France

Location

University General Hospital of Ioannina

Ioannina, Greece

Location

METROPOLITAN HOSPITAL, Piraeus

Piraeus, Greece

Location

Policlinico di Catanzaro - A.O.U. Mater Domini

Catanzaro, Calabria, 88100, Italy

Location

Ospedale Sant'Anna e San Sebastiano

Caserta, Campania, 81100, Italy

Location

Policlinico Federico II di Napoli

Naples, Campania, 80131, Italy

Location

Policlinico Sant'Orsola - Università di Bologna

Bologna, Emilia-Romagna, 40138, Italy

Location

Arcispedale Sant'Anna - Università degli Studi di Ferrara

Ferrara, Emilia-Romagna, 44124, Italy

Location

Ospedale Civile di Baggiovara - A.O.U. di Modena

Modena, Emilia-Romagna, 41124, Italy

Location

DIMI - Dipartimento di Medicina Interna, Università di Genova

Genova, GE, 16132, Italy

Location

ARNAS Garibaldi

Catania, Italy, Italy

Location

Policlinico Umberto I - Sapienza Università di Roma

Rome, Lazio, 00161, Italy

Location

Ospedale Bassini - ASST Nord Milano

Milan, Lombardy, 20092, Italy

Location

Policlinico Paolo Giaccone - Università degli Studi di Palermo

Palermo, Sicily, 90127, Italy

Location

Ospedale San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

Location

A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette

Torino, Torino, 10126, Italy

Location

CNR Gabriele Monasterio - Centro di Aferesi, Pisa

Pisa, Tuscany, 56124, Italy

Location

Policlinico di Padova - A.O.U. di Padova

Padua, Veneto, 35128, Italy

Location

Ospedale Borgo Trento - A.O.U. Integrata Verona

Verona, Veneto, 37126, Italy

Location

Ospedale regionale generale "F. Miulli"

Bari, Italy

Location

Radboud University Medical Centre

Nijmegen, Netherlands

Location

Rotterdam Erasmus Medical Center

Rotterdam, Netherlands

Location

Queen Elizabeth Hospital Birmingham (QEII - Birmingham)

Birmingham, England, United Kingdom

Location

Harefield Hospital - Royal Brompton & Harefield NHS Foundation Trust

Harefield, England, United Kingdom

Location

Hammersmith Hospital - Imperial College Healthcare NHS Trust

London, England, W12 0HS, United Kingdom

Location

Manchester University Hospital - NHS Foundation Trust

Manchester, England, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected and retained for lipid profile analysis, liver function tests (ALT, AST, GGT), and other biochemical assessments related to the study objectives. No genetic testing or DNA extraction will be performed on the retained samples.

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia; Dyslipidemias; Hypercholesterolemia; Cardiovascular Diseases; Lipid Metabolism Disorders; Atherosclerosis

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 18, 2025
• Study Start: September 9, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2); NL (2); IT (17); FR (5); GB (4)