Clinical trial NCT06832371: Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Official 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Homozygous Familial Hypercholesterolemia (HoFH)
Major Adverse Cardiovascular Events (MACE)
Dyslipidemia
Keywords: Lomitapide
Hypercholesterolemia
Cardiovascular Disease
LDL Cholesterol
Lipid-Lowering Therapy
Lipid Metabolism Disorders
Atherosclerosis
Rare Genetic Disorders
Lead sponsor: Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)
Sponsor class: OTHER
Collaborators: name: Amryt Pharmaceuticals DAC
name: Clinical Trial Consulting
name: CMV-Stat S.r.l.
First posted: 2025-02-18
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

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.

Detailed description: 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 \>26 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Major Adverse Cardiovascular Events (MACE) Before and After Lomitapide Treatment
timeFrame: 3 years before treatment vs. 3 years during treatment
Secondary outcomes:
measure: Change in LDL-Cholesterol Levels
timeFrame: Baseline, 1 year, 2 years, 3 years
measure: Change in Total Cholesterol, Triglycerides, and HDL-Cholesterol
timeFrame: Baseline, 1 year, 2 years, 3 years
measure: Change in Triglyceride Levels
timeFrame: Baseline, 1 year, 2 years, 3 years.
measure: Change in HDL-Cholesterol Levels
timeFrame: Baseline, 1 year, 2 years, 3 years
measure: Liver Safety Profile - ALT Levels
timeFrame: Baseline, 1 year, 2 years, 3 years.
measure: Liver Safety Profile - AST Levels
timeFrame: Baseline, 1 year, 2 years, 3 years.
measure: Liver Safety Profile - GGT Levels
timeFrame: Baseline, 1 year, 2 years, 3 years.
measure: Lipid-Lowering Therapy Modifications
timeFrame: Baseline, 1 year, 2 years, 3 years.
Other outcomes:
measure: Biomarkers of Liver and Vascular Damage
timeFrame: Baseline and after 3 years of lomitapide treatment.
measure: Presence and Severity of Hepatic Steatosis
timeFrame: After 3 years of lomitapide treatment.
measure: Liver Elastography Parameters
timeFrame: After 3 years of lomitapide treatment.
measure: Dietary Records
timeFrame: After 3 years of lomitapide treatment.
measure: Adherence to Lipid-Lowering Medications
timeFrame: After 3 years of lomitapide treatment.
Locations:
city: Lille
country: France
facility: CHRU Lille - Centre Hospitalier Universitaire de Lille
city: Lyon
country: France
facility: Centre Hospitalier Universitaire de Lyon (CHU Lyon)
city: Marseille
country: France
facility: Hôpital La Timone - Assistance Publique Hôpitaux de Marseille (AP-HM)
city: Paris
country: France
facility: Hôpital La Pitié Salpêtrière - Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix"
city: Strasbourg
country: France
facility: Strasbourg University Hospital (CHU Strasbourg)
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
city: Piraeus
country: Greece
facility: METROPOLITAN HOSPITAL, Piraeus
city: Catanzaro
country: Italy
facility: Policlinico di Catanzaro - A.O.U. Mater Domini
state: Calabria
city: Caserta
country: Italy
facility: Ospedale Sant'Anna e San Sebastiano
state: Campania
city: Napoli
country: Italy
facility: Ospedale Monaldi - AORN dei Colli, Napoli
state: Campania
city: Napoli
country: Italy
facility: Policlinico Federico II di Napoli
state: Campania
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola - Università di Bologna
state: Emilia-Romagna
city: Ferrara
country: Italy
facility: Arcispedale Sant'Anna - Università degli Studi di Ferrara
state: Emilia-Romagna
city: Modena
country: Italy
facility: Ospedale Civile di Baggiovara - A.O.U. di Modena
state: Emilia-Romagna
city: Genova
country: Italy
facility: DIMI - Dipartimento di Medicina Interna, Università di Genova
state: GE
city: Roma
country: Italy
facility: Policlinico Umberto I - Sapienza Università di Roma
state: Lazio
city: Milano
country: Italy
facility: Ospedale Bassini - ASST Nord Milano
state: Lombardia
city: Palermo
country: Italy
facility: Policlinico Paolo Giaccone - Università degli Studi di Palermo
state: Sicilia
city: Orbassano
country: Italy
facility: Ospedale San Luigi Gonzaga
state: Torino
city: Pisa
country: Italy
facility: CNR Gabriele Monasterio - Centro di Aferesi, Pisa
state: Toscana
city: Padova
country: Italy
facility: Policlinico di Padova - A.O.U. di Padova
state: Veneto
city: Verona
country: Italy
facility: Ospedale Borgo Trento - A.O.U. Integrata Verona
state: Veneto
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
city: Rotterdam
country: Netherlands
facility: Rotterdam Erasmus Medical Center
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham (QEII - Birmingham)
state: England
city: Harefield
country: United Kingdom
facility: Harefield Hospital - Royal Brompton & Harefield NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Hammersmith Hospital - Imperial College Healthcare NHS Trust
state: England
city: Manchester
country: United Kingdom
facility: Manchester University Hospital - NHS Foundation Trust
state: England
Study officials:
References: