Intensifying lipid-lowering with evinacumab to reduce coronary plaque in homozygous familial hypercholesterolemia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter, international, observational study using both retrospective and prospective data to compare HoFH patients who received intensified lipid-lowering that includes evinacumab with those on conventional therapy. Coronary computed tomography angiography (CCTA) is used to quantify total plaque volume and differentiate plaque types at baseline and 18–24 months follow-up. Participants are recruited from about 25 European centers and include adolescents and adults meeting consensus diagnostic criteria for HoFH, with specific imaging availability requirements. The study leverages real-world clinical care to describe how adding an ANGPTL3 antibody affects plaque burden outside of randomized trials.

Why it matters

Who can join: the full rules

Inclusion Criteria (intensified treatment group - Evinacumab):

1. Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
2. Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
3. Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
4. 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.
5. 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.
6. LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.

Inclusion criteria (conventional treatment group - No Evinacumab)

1. Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
2. Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
3. Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
4. 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.
5. LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.

Exclusion criteria (intensified treatment group - Evinacumab)

1. Patients participating in a clinical trial with an investigational drug within the last 6 months.
2. Patients treated outside of Evinacumab approved indication.
3. Inability to access adequate retrospective clinical data from medical records.
4. Inability or unwillingness to provide informed consent/assent or refusal to participate.
5. Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
6. Pregnancy at the time of the LLT administration.
7. 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)

1. Participation in any interventional clinical trial involving investigational drugs within the last 6 months.
2. Inability to access adequate retrospective clinical data from medical records.
3. Inability or unwillingness to provide informed consent/assent or refusal to participate.
4. Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
5. Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.
6. Pregnancy at the time of the LLT administration.

Where it's running

• Unité de Lipidologie et Prévention Cardiovasculaire, Centre de Compétence Dyslipidémies Rares (CEDRA), Service de Nutrition, Hôpital Pitié-Salpétriêre
  Paris, France Recruiting
• Dipartimento Scienze-Cardiovascolari, AO "Sant'Anna e San Sebastiano" di Caserta
  Caserta, Italy Recruiting
• U.O.C. di Medicina Interna, P.O. Nesima, ARNAS Garibaldi
  Catania, Italy Recruiting
• Nefrologia e Emodialisi, Centro Aterosclerosi e Dislipidemie, Ospedale Bassini, ASST Nord Milano
  Cinisello Balsamo, Italy Recruiting
• Malattie Aterotrombotiche, Azienda Ospedaliero Universitaria Careggi
  Florence, Italy Recruiting
• DAI di Medicina Clinica, Centro di Riferimento Regionale di Lipidologia e Dislipidemie, AOU Federico II di Napoli
  Naples, Italy Recruiting

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.