Studying how lomitapide treatment affects the risk of serious heart problems in people with a rare inherited high cholesterol condition
| ISRCTN | ISRCTN94783078 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN94783078 |
| IRAS number | 345905 |
| Secondary identifying numbers | Version 2.2 Feb 14 2025 |
- Submission date
- 12/06/2025
- Registration date
- 07/07/2025
- Last edited
- 20/06/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening condition characterized by a severe elevation of LDL cholesterol (LDL-C) and accelerated atherosclerosis. In these patients, an aggressive therapy to reduce LDL-C is mandatory to control the high risk of CHD associated with this disease. Lomitapide has been demonstrated to be very effective in reducing LDL-C in HoFH in both clinical trial and real-world experience. However, limited information is available on how this drug affects cardiovascular risk. Due to the rarity of the disease, a randomized controlled trial testing the effect of lomitapide on the incidence of major adverse cardiovascular events (MACE) is not feasible.
To overcome this, an observational study with the aim of analyzing the occurrence of MACE in HoFH patients exposed to lomitapide will be performed. In the Italian network of lipid centres, information about MACE in HoFH patients exposed to lomitapide is available for more than 30 patients. The duration of follow-up among these patients was not homogenous. In fact, there was a group of patients with barely 1 year of treatment and this may not represent a sufficient time to observe any detectable benefit on cardiovascular risk, especially in adult HoFH patients exposed to high levels of LDL-C since birth. Therefore, to provide a better estimation of the effect of lomitapide therapy on MACE, we have designed this observational study with a retrospective phase in which the data available will be collected, followed by a prospective phase where all patients will be followed up to completion of at least 3 years of treatment. As a parallel cohort of untreated HoFH is not available, we have decided to compare the occurrence of MACE during the 3-year period of lomitapide treatment with that which occurred in the same cohort during the 3-year period before initiation of lomitapide.
Who can participate?
Patients aged 18 years and over with homozygous familial hypercholesterolemia treated with lomitapide at any dosage for at least 12 months
What does the study involve?
All the tests and observations are made according to standard of care:
Patient demographic information (weight, BMI): sex, age, ethnicity and height.
Physical examination, vital signs (blood pressure and heart rate).
Medical history, including the genetic diagnosis (if available).
MACE assessment, Serious Adverse Events (SAEs).
Prior and concomitant lipid-lowering therapies.
Laboratory data: e.g. plasma lipids and liver function tests.
Liver MRI or ultrasound to assess the presence and severity of hepatic steatosis at baseline, if available (within the year before first lomitapide prescription).
Liver elastography or fibroscan at baseline, if available (within the year before first lomitapide prescription).
The maximum duration of the study will be about 3 years.
What are the possible benefits and risks of participating?
Benefits: There is no direct benefit from taking part in this study. However, the study can contribute to improving scientific knowledge of lomitapide therapy, HoFH clinical conditions, including its treatment management and quality of life in patients with HoFH.
Risks: As the registry is an observational study, the patients are not required to take any additional medication, treatment procedures or diagnostic tests as part of their study participation. About the risks and side effects associated with lomitapide (Lojuxta®), please refer to the Summary of Products Characteristics.
Where is the study run from?
More than 26 sites from Europe (Italy, Greece, France, the Netherlands and the United Kingdom) will participate in the study. The study is run from an Italian Sponsor (Fondazione SISA).
When is the study starting and how long is it expected to run for?
February 2024 to September 2027
Who is funding the study?
Fondazione SISA (Italy)
Who is the main contact?
Prof. Alberico Catapano, alberico.catapano@gmail.com
Contact information
Public, Scientific
Via Giuseppe Balzaretti, 7
Milano
20133
Italy
 ORCID ID |
0000-0002-7593-2094 |
|---|---|
| Phone | +39 (0)2 49637591 |
| alberico.catapano@unimi.it |
Principal Investigator
Cane Road
London
W12 0HS
United Kingdom
| ORCID ID |
0000-0003-1168-0366 |
|---|---|
| Phone | +44 (0)7775557295 |
| j.cegla@imperial.ac.uk |
Study information
| Study design | Observational multicenter international open-label retrospective and prospective study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Evaluation of the effect of lomitapide treatment on major adverse cardiovascular events in patients with homozygous familial hypercholesterolemia |
| Study acronym | LILITH |
| Study objectives | Due to the rarity of the disease, a randomized controlled trial testing the effect of lomitapide on the incidence of major adverse cardiovascular events (MACE) is not feasible. To overcome this, an observational study with the aim of analyzing the occurrence of MACE in HoFH patients exposed to lomitapide will be performed. |
| Ethics approval(s) |
Approved 30/01/2025, East Midlands - Leicester Central Research Ethics Committee (2 Redman Place, London, E20 1JQ, United Kingdom; +44 (0)207 104 8066, +44 (0)207 104 8227, +44 (0)207 104 8284; leicestercentral.rec@hra.nhs.uk), ref: 24/EM/0275 |
| Health condition(s) or problem(s) studied | MACE in patients with familial hypercholesterolemia |
| Intervention | All the tests and observations are made according to standard of care: Patient demographic information (weight, BMI); sex, age, ethnicity and height will be collected once at Y-3. Physical examination, vital signs (blood pressure and heart rate) Medical history will be collected once at Y-3, including the genetic diagnosis (if available). MACE assessment, Serious Adverse Events (SAEs). Prior and concomitant lipid-lowering therapies. Laboratory data: for plasma lipids and liver function test (Total Cholesterol, HDL, Triglycerides, LDL-C, ALT, AST, GGT). Apolipoprotein B, lipoprotein(a), hematology (i.e. complete blood count), glucose, glycated hemoglobin, albumin, coagulation (PT, PTT and fibrinogen), creatinine, BUN, CPK, C-reactive protein, and CK18F will be requested at baseline visit retrospectively only if these results are already available in medical records. Liver MRI or ultrasound to assess the presence and severity of hepatic steatosis at baseline, if available (within the year prior to first lomitapide prescription). For liver MRI data, liver fat fraction will be assessed. For liver ultrasound, information on the severity of liver steatosis (absent, mild, moderate, severe) will be collected. Liver elastography or fibroscan at baseline, if available (within the year prior to first lomitapide prescription). For liver elastography, information on Acoustic Radiation Forced Impulse (ARFI) and Controlled Attenuation Parameter (CAP). For fibroscan data, liver stiffness (Kpa) and CAP will be collected. The maximum duration of the study will be 37 months, which is approximately 3 years. |
| Intervention type | Other |
| Primary outcome measure | The incidence of major adverse cardiovascular events (MACE) is assessed using medical records and hospital discharge summaries. Events are adjudicated by an independent expert committee. Timepoints: retrospectively at each timepoint during the 3 years prior to lomitapide initiation, and prospectively during the 3 years of lomitapide treatment. |
| Secondary outcome measures | 1. LDL-C and plasma lipid levels (Total Cholesterol, HDL, Triglycerides, LDL-C) are measured using standard laboratory blood tests at each timepoint during the 3 years prior to lomitapide initiation, and prospectively during the 3 years of lomitapide treatment 2. Liver function tests (ALT, AST, GGT) are measured using standard laboratory blood tests at each timepoint during the 3 years prior to lomitapide initiation, and prospectively during the 3 years of lomitapide treatment 3. Lipid-lowering treatment (LLT) changes, including discontinuation of LDL apheresis or addition of new agents, are collected via investigator medical records at each timepoint during the 3 years prior to lomitapide initiation, and prospectively during the 3 years of lomitapide treatment 4. MACE incidence assessed using alternative definitions (3-point and 4-point MACE), based on medical records and adjudicated by the expert committee at each timepoint during the 3 years prior to lomitapide initiation, and prospectively during the 3 years of lomitapide treatment |
| Overall study start date | 01/02/2024 |
| Completion date | 30/09/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 72 |
| Key inclusion criteria | 1. Adult patients (age ≥18 years) 2. Patients with clinical or genetic diagnosis of HoFH who were treated with lomitapide at any dosage 3. On treatment with lomitapide for at least 12 months at the time of enrollment 4. Availability of 3 years medical records prior to the commencement of lomitapide treatment to confirm the occurrence of MACE events 5. Patients who have the ability to understand the requirements of the study and provide written informed consent to comply with the requirements |
| Key exclusion criteria | 1. Patients who were prescribed lomitapide outside of the marketing authorization or in contraindicated patients 2. Patients who are receiving lomitapide in clinical trials 3. 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 time of enrolment |
| Date of first enrolment | 09/09/2024 |
| Date of final enrolment | 31/08/2025 |
Locations
Countries of recruitment
- England
- France
- Greece
- Italy
- Netherlands
- United Kingdom
Study participating centres
Cane Road
London
W12 0HS
United Kingdom
London
SE1 9RT
United Kingdom
Birmingham
B15 2GW
United Kingdom
Manchester
UK M13 9WL
United Kingdom
Roma
00161
Italy
Caserta
81100
Italy
Palermo
90127
Italy
Bologna
40138
Italy
Napoli
80131
Italy
Cinisello Balsamo
20092
Italy
Catanzaro
88100
Italy
Orbassano
10043
Italy
Modena
41124
Italy
Ferrara
44124
Italy
Verona
37126
Italy
Catania
95122
Italy
Acquaviva delle Fonti
70021
Italy
Padova
35128
Italy
Genova
16132
Italy
Torino
10126
Italy
Pisa
56124
Italy
Paris
75013
France
Strasbourg
67098
France
LILLE
59037
France
MARSEILLE
13385
France
Rotterdam
3015 GD
Netherlands
Nijmegen
6525 GA
Netherlands
Piraeus
185 47
Greece
Ioannina
455 00
Greece
Sponsor information
Research organisation
Via Giuseppe Balzaretti 7
Milano
20133
Italy
| Phone | +39 (0)2 49637591 |
|---|---|
| fondazione@sisa.it | |
| Website | http://www.sisa.it |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/09/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The sponsor will present the results of this trial in a final Clinical Study Report (CSR) in accordance with GCP and all other regulatory obligations. The study results will be published and/or presented at scientific meetings. The sponsor is the owner of the data resulting from this clinical trial. Once the study has been closed and the Study Coordinator has presented the main study publication, any participating Centre may use its own data (data generated in its own centre) for educational purposes, publications and presentations. These may be sent to the sponsor for approval with a 15-day notice for abstracts, presentations or educational material and a 30-day notice for publications. |
| IPD sharing plan | The datasets generated during and/ora analysed during the current studi will be available upon request from Prof. Alberico Luigi Catapano (fondazione@sisa.it) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.2 | 14/02/2025 | 20/06/2025 | No | No |
Additional files
Editorial Notes
12/06/2025: Study's existence confirmed by the East Midlands - Leicester Central Research Ethics Committee.
