Alirocumab and Plaque Burden In Familial Hypercholesterolaemia

NCT05465278 | Completed Phase 4

• 1 other identifier: ARCHITECT
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Low-level, open-label, multicenter clinical trial to evaluate the effect of alirocumab on the volume, architecture and composition of atherosclerotic plaque in patients with Familial hypercholesterolemia from the SAFEHEART Registry. ARCHITECT study

Conditions

Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Change in atherosclerotic plaque burden (%) assessed by coronary computed tomography

  change in plaque burden assessed by coronary computed tomography at enrollemnt and at follow-up. Coronary plaque burden and its cgaracteristics will be analysed ant enrollment and at the end of the follow-up

  18 months

Secondary Outcomes (1)

• Changue in plaque volume (mm3) assessed by coronary computed tomography

  18 months

Study Arms (1)

Alirocumab

EXPERIMENTAL

Every patient enrolled witll receive treatment witl Alirocumab

Drug: Alirocumab

Interventions

Alirocumab DRUG

18 months treatment with alirocumab

Alirocumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have voluntarily granted informed consent (preferably in writing or, failing that, orally before independent witnesses of the research team) before carrying out the specific procedures of the trial.
• Patients of both sexes aged between 35 and 65 years.
• Patients with a molecular diagnosis of heterozygous HF included in the Spanish SAFEHEART registry (http://safeheart.colesterolfamiliar.org/).
• Asymptomatic patients.
• Patients without a previous history of clinical cardiovascular events (acute myocardial infarction \[AMI\], stroke, coronary revascularization, etc.).
• Patients on optimized and stable treatment with maximum tolerated doses of a statin with or without other lipid-lowering therapies, for at least 3 months, with inadequate control, defined by a LDL-C level\> 100 mg / dL.
• Availability of a coronary CTA performed in the 3 months prior to the baseline visit. If a coronary CTA is not available, this test will be performed during the selection period.
• ATC of at least 64 cuts performed in a center with sufficient experience (more than 100 ACTs per year).
• Patients with a PVA\> 30% in the baseline coronary CTA, performed in the last 3 months before the baseline visit.
• Patients in whom treatment with alirocumab 150 mg / mL is indicated, according to the characteristics of the patient and the Praluent® technical data sheet.

You may not qualify if:

• Class\> II heart failure according to the functional classification of the NYHA scale (New York Heart Association).
• Heart rate different from normal sinus rhythm (regular HR between 60-100 bpm).
• Previous history of AMI, angina, peripheral arterial thrombosis, stroke or transient ischemic attack (TIA).
• Uncontrolled hypertension defined as a resting systolic blood pressure value\> 180 mmHg at the baseline visit.
• Fasting triglyceride levels\> 250 mg / dl at baseline visit.
• Type 1 diabetes or insufficiently controlled type 2 diabetes (HbA1\> 9%).
• Personal or family history of inherited muscle disorders.
• Known thyroid disease or thyroid replacement therapy.
• Glomerular filtration rate \<60 ml / min / 1.73 m2 at baseline visit.
• Elevated ALT and / or AST levels (\> 3 times the ULN at the baseline visit).
• Elevated creatinine kinase levels (\> 3 times ULN at baseline).
• Patients who have previously received iPCSK9, CETP (cholesterol ester transport protein) inhibitors, mipomersen and / or lomitapide.
• Patients with statin intolerance.
• Active cancer or previous history of cancer.
• Clinically relevant active infection or clinically significant hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction.

Sponsors & Collaborators

• Fundación Hipercolesterolemia Familiar: lead

Study Sites (1)

Fundacion Hipercolesterolemia Familiar

Madrid, 28010, Spain

Location

Related Publications (2)

• Perez de Isla L, Diaz-Diaz JL, Romero MJ, Muniz-Grijalvo O, Mediavilla JD, Argueso R, de Andres R, Fuentes F, Sanchez Munoz-Torrero JF, Rubio P, Alvarez-Banos P, Manas D, Suarez Gutierrez L, Saltijeral Cerezo A, Mata P; SAFEHEART Investigators. Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study. Circ Cardiovasc Imaging. 2024 Jan;17(1):e016206. doi: 10.1161/CIRCIMAGING.123.016206. Epub 2024 Jan 11.

  PMID: 38205656 DERIVED

• Perez de Isla L, Diaz-Diaz JL, Romero MJ, Muniz-Grijalvo O, Mediavilla JD, Argueso R, Sanchez Munoz-Torrero JF, Rubio P, Alvarez-Banos P, Ponte P, Manas D, Suarez Gutierrez L, Cepeda JM, Casanas M, Fuentes F, Guijarro C, Angel Barba M, Saltijeral Cerezo A, Padro T, Mata P; SAFEHEART Study Group. Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study. Circulation. 2023 May 9;147(19):1436-1443. doi: 10.1161/CIRCULATIONAHA.122.062557. Epub 2023 Apr 3.

  PMID: 37009731 DERIVED

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Low-intervention, open-label, multicenter, phase IV clinical trial to evaluate the effect 18 months after initiation of alirocumab (Praluent®) on the volume, architecture, and composition of the coronary atheroma plaque in subjects with FH and without clinical cardiovascular disease followed in the SAFEHEART registry in optimized and stable treatment with maximum tolerated doses of statins with or without other lipid-lowering treatments under clinical practice conditions.

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: July 19, 2022
• Study Start: May 1, 2018
• Primary Completion: March 30, 2022
• Study Completion: March 30, 2022
• Last Updated: July 19, 2022

Record last verified: 2022-07

Locations

ES (1)