Assessing the Impact of Intensification of Lipid Lowering Therapy With Guidelines-based Evinacumab Administration on Coronary Plaque Volumes Measured by Coronary Computed Tomography Angiography (CCTA) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
Recruiting · NCT07447648 · Observational (researchers observe without assigning treatment) · Lead sponsor: Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)
View the official record on ClinicalTrials.gov →What this trial is about
This observational, multicenter, retrospective and prospective study aims to evaluate the impact of intensified lipid-lowering therapy including Evinacumab on coronary atherosclerotic plaque burden in patients with Homozygous Familial Hypercholesterolemia (HoFH). HoFH is a rare genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels from early life and a markedly increased risk of premature atherosclerotic cardiovascular disease. Despite combination lipid-lowering therapy, many patients do not achieve recommended LDL-C targets and remain at high cardiovascular risk. Evinacumab, a monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3), has demonstrated significant LDL-C reduction in clinical trials. However, real-world evidence on its impact on coronary plaque progression is limited. The study will compare HoFH patients receiving intensified lipid-lowering therapy including Evinacumab with patients receiving conventional lipid-lowering therapy without Evinacumab. Coronary plaque burden and phenotype will be assessed using coronary computed tomography angiography (CCTA) performed as part of routine clinical practice. Approximately 52 patients will be enrolled across European centers. The primary objective is to evaluate changes in non-calcified coronary plaque volume between baseline and 18-24 months' follow-up. Secondary objectives include evaluation of total plaque burden, high-risk plaque characteristics, and LDL-C reduction. Exploratory analyses will assess patient-reported outcomes, pericoronary adipose tissue characteristics, and supravalvular atherosclerosis. All data are collected from routine clinical care. No additional procedures are mandated by the protocol. This study aims to generate real-world imaging evidence on the effect of intensified lipid-lowering therapy including Evinacumab on coronary atherosclerosis in HoFH.
Who can take part
Inclusion criteria
- intensified treatment group - Evinacumab):
- Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
- Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
- Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
- Patients who initiated Evinacumab (at the approved dosage and administration) within 24 months before enrolment as add-on to lipid-lowering treatment (with statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before Evinacumab initiation, as per routine clinical care and no change in dosing is anticipated.
- Availability of a baseline CCTA performed at least 6 months prior or 1 month after Evinacumab initiation and a follow-up CCTA performed 18-24 months after Evinacumab initiation.
- LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.
- Inclusion criteria (conventional treatment group - No Evinacumab)
- Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
- Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
- Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
- Patients with HoFH on standard lipid-lowering therapy (statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before a baseline CCTA and with a follow-up CCTA after 18-24 months from the baseline one.
- Required lipid lowering therapies: statin, ezetimibe and PCSK9 directed therapy (unless discontinuation due to \<15% LDL-cholesterol reduction).
- Optional additional lipid-lowering therapies:
- Lipoprotein apheresis, at stable intervals for at least 3 months.
- Lomitapide, at stable dose for at least 3 months.
- LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.
Exclusion criteria
- intensified treatment group - Evinacumab)
- Patients participating in a clinical trial with an investigational drug within the last 6 months.
- Patients treated outside of Evinacumab approved indication.
- Inability to access adequate retrospective clinical data from medical records.
- Inability or unwillingness to provide informed consent/assent or refusal to participate.
- Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
- Pregnancy at the time of the LLT administration.
- Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.
- Exclusion criteria (conventional treatment group - No Evinacumab)
- Participation in any interventional clinical trial involving investigational drugs within the last 6 months.
- Inability to access adequate retrospective clinical data from medical records.
- Inability or unwillingness to provide informed consent/assent or refusal to participate.
- Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
- Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.
- Pregnancy at the time of the LLT administration.
Where it is running
13 locations listed.
- Amsterdam University Medical Center, Amsterdam UMC, locatie AMC - Amsterdam, Netherlands
- Ege University,Director of Lipid and Prevention Clinic, Department of Cardiology - Bornova, Turkey (Türkiye)
- Dipartimento Scienze-Cardiovascolari, AO "Sant'Anna e San Sebastiano" di Caserta - Caserta, Italy
- U.O.C. di Medicina Interna, P.O. Nesima, ARNAS Garibaldi - Catania, Italy
- Nefrologia e Emodialisi, Centro Aterosclerosi e Dislipidemie, Ospedale Bassini, ASST Nord Milano - Cinisello Balsamo, Italy
- Malattie Aterotrombotiche, Azienda Ospedaliero Universitaria Careggi - Florence, Italy
- DAI di Medicina Clinica, Centro di Riferimento Regionale di Lipidologia e Dislipidemie, AOU Federico II di Napoli - Naples, Italy
- UOC Clinica Medica I, AOU di Padova - Padova, Italy
- U.O. Astanteria/MCAU AOU, Policlinico "Paolo Giaccone" di Palermo - Palermo, Italy
- Unité de Lipidologie et Prévention Cardiovasculaire, Centre de Compétence Dyslipidémies Rares (CEDRA), Service de Nutrition, Hôpital Pitié-Salpétriêre - Paris, France
- Centro per le Malattie Rare del Metabolismo dei Lipidi, Unità di Medicina Interna e Malattie Metaboliche, Dipartimento di Medicina Traslazionale e di Precisione Sapienza, Università di Roma - Roma, Italy
- Erasmus University Medical Center, Dr. Molewaterplein 40 - Rotterdam, Netherlands
- Medicina Interna, Ospedale Molinette, AOU Città della Salute e della Scienza - Torino, Italy