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Recruiting NCT07427472

"Detection and Follow-up of Coronary Lesions in HeFH (DESTINY-FH Study)"

No phase Interventional Heterozygous Familial Hypercholesterolemia (HeFH)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Coronary computed tomography angiography.
Who it may be relevant to
Registry conditions: Heterozygous Familial Hypercholesterolemia (HeFH). Basic parameters: 30 years — 60 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Detection and Longitudinal Follow-up of Non-calcified and Calcified Coronary Lesions in Heterozygous Familial Hypercholesterolemia (DESTINY-FH)

Overview

This multicenter, non-randomized interventional study aims to assess coronary artery disease progression over 5 years in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH), using coronary computed tomography angiography (CCTA). The primary endpoint is the visual evaluation of coronary stenosis using CAD-RADS v2.0, identifying changes between baseline (2018-2022) and study inclusion. The study will enroll 300 patients (100 protected, 200 non-protected) from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Participation lasts up to one week. Total study duration is 2 years, with extended follow-up through routine care data over 10 years.

Detailed description

HeFH is an autosomal dominant genetic disorder characterized by lifelong elevated LDL-C levels, which significantly increase the risk of premature coronary atherosclerosis. Cardiovascular risk stratification in HeFH remains challenging due to limitations of traditional risk scores and stress testing. The coronary artery calcium (CAC) score is a useful tool for reclassifying cardiovascular risk but fails to detect non-calcified plaques, which may be prevalent in HeFH despite a CAC score of zero. Previous studies suggest a prevalence of non-calcified plaques as high as 30% in molecularly diagnosed HeFH patients.

This multicenter interventional, non-randomized comparative study aims to evaluate the progression of coronary artery disease over a 5-year period in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH). Using coronary computed tomography angiography (CCTA), the study will assess both calcified and non-calcified plaque burden in this high-risk population.

The primary outcome is the visual, semi-quantitative evaluation of coronary stenosis severity using CAD-RADS v2.0 classification to identify high-risk plaques and categorize patients as having regression, stability, or progression of coronary disease based on changes in CAD-RADS categories between baseline (2018-2022) and the DESTINY-FH study visit.

The study will enroll 300 patients (100 "protected" and 200 "non-protected") from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Individual participation will last from one day to one week. Total study duration is 2 years, with additional 10-year follow-up using routinely collected medical records.

Interventions

  • Other Coronary computed tomography angiography
    Coronary computed tomography angiography with injection of iodinated contrast material

Primary outcome measures

  • Progression of coronary artery disease over 5 years in patients with heterozygous familial hypercholesterolemia [Time frame: 1 day]
Secondary outcome measures (12)
  • Change in total coronary plaque volume, lesion type, and proximal aortic calcifications. [Time frame: 1 day]
  • Survival curve of major cardiovascular events incidence. [Time frame: 1 day]
  • Cox regression analysis of cardiovascular event occurrence and associated clinical, biological, and omics data. [Time frame: 1 day]
  • Linear regression of clinical and biological variables by CAD-RADS category change. [Time frame: 1 day]
  • Comparison of omics data by plaque volume change and CAD-RADS category shift. [Time frame: 1 day]
  • Baseline prevalence of carotid plaque by group [Time frame: 1 day]
  • Baseline prevalence of femoral plaque by group [Time frame: 1 day]
  • Baseline aortic valve calcium score by group [Time frame: 1 day]
  • Baseline thoracic aorta calcium score by group [Time frame: 1 day]
  • Baseline diameters of the ascending and descending aorta by group [Time frame: 1 day]
  • Correlation between baseline carotid plaque presence and change in coronary plaque volume [Time frame: Baseline to 5 years]
  • Correlation between baseline femoral plaque presence and change in coronary plaque volume [Time frame: Baseline to 5 years]

Eligibility criteria

Inclusion criteria

  • Patients with heterozygous familial hypercholesterolemia
  • Aged 30 to 60 years.
  • Patients who underwent a CAC score and a coronary CT angiogram at least 5 years ago, exclusively at the same imaging center (ICT de la Pitié Salpetrière).
  • Patient asymptomatic for exertional chest pain at the time of CCTA
  • Clinical examination performed
  • Beneficiary of a social protection scheme or entitled person (excluding AME)
  • Patient informed and consent form signed

Exclusion criteria

  • Patient under guardianship, or unable to give consent
  • Pregnancy, breast-feeding
  • Technical contraindication: weight > 250 kg
  • Simultaneous participation in other interventional research involving the human body, or period of exclusion following previous research involving the human body still in progress.
  • Adults subject to a legal protection order
  • Contraindication to esmolol and/or atenolol
  • Only for patients who need to undergo a CT angiogram and a thoraco-abdominal-pelvic CT scan:
  • Renal insufficiency (LC<60)
  • Unbalanced diabetes when acquiring a previous coronary angioscanner
  • Personal history of cardiovascular disease and myocardial infarction at the time of CCTA
  • Contraindication to iodinated contrast media
  • Patient having already had an adverse event (AE) during the acquisition of a prior coronary angioscanner

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Prevention

Study locations

France · 3 centers
  • Plateau d'investigation clinique (PIC) IHU-ICAN — Paris
  • APHP- Hospital Saint-Antoine — Paris
  • APHP-Sorbonne, Pitié Salpêtrière Hospital — Paris

Identifiers

NCT: NCT07427472 · APHP250574

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗