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Carotid Ultrasound-Based Strategy for Primary Prevention of Cardiovascular Events in Inflammatory Rheumatic Disease (PREVENER) (PREVENER)

20 mai 2026 mis à jour par: Instituto de Investigación Marqués de Valdecilla

Randomized Clinical Trial to Assess the Efficacy and Safety of a Primary Prevention Strategy for Cardiovascular Events in Patients With Inflammatory Rheumatic Diseases Based on the Use of Carotid Ultrasound

PREVENER is a randomized, open-label, multicenter, phase IV clinical trial designed to evaluate the efficacy and safety of a carotid ultrasound-based strategy for the primary prevention of cardiovascular events in patients with inflammatory rheumatic diseases (IRD).

Patients with IRD, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), and systemic lupus erythematosus (SLE), have a 50% higher risk of cardiovascular (CV) events compared to the general population. However, conventional CV risk scores (SCORE2/OP) systematically underestimate this risk, leaving many high-risk patients without appropriate preventive treatment.

Patients aged ≥50 years with IRD and low-to-moderate CV risk according to SCORE2/OP will be randomized 1:1 to either an experimental group (carotid ultrasound to detect subclinical atherosclerosis) or a control group (standard care according to ESC 2021 guidelines). Patients in the experimental group with carotid plaques will be reclassified as very high CV risk and treated with high-intensity statins (LDL target <55 mg/dL). The primary endpoint is the incidence of major adverse cardiovascular events (MACE) over 48 months of follow-up.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

Background:

Patients with chronic inflammatory rheumatic diseases (RA, PsA, AxSpA, SLE) carry a significantly increased risk of atherosclerotic cardiovascular events compared to the general population. This excess risk is largely attributed to the pro-atherogenic effect of chronic inflammation. Despite this, conventional CV risk stratification tools such as SCORE2/OP do not account for inflammation-related risk, leading to systematic underestimation of CV risk in these patients. Data from the CARMA project demonstrated that 53% of CV events in Spanish patients with IRD occurred in those classified as low-to-moderate risk by SCORE2/OP, highlighting the urgent need for improved risk stratification strategies.

Carotid ultrasound for the detection of subclinical atherosclerosis (carotid plaques) has been proposed as a modifier of CV risk in the ESC 2021 guidelines. The presence of carotid plaques automatically reclassifies individuals to very high CV risk, warranting intensive lipid-lowering therapy. However, no randomized clinical trial has evaluated the efficacy of this strategy in patients with IRD.

Study Design:

PREVENER is an open-label, randomized, multicenter, phase IV clinical trial. Patients aged ≥50 years with IRD (RA by ACR/EULAR 2010 criteria, PsA by CASPAR criteria, AxSpA by ASAS criteria, or SLE by ACR/EULAR 2019 criteria) and low-to-moderate CV risk according to SCORE2/OP will be enrolled across 17 Spanish hospitals.

Eligible patients will be randomized 1:1 to:

  • Experimental group: carotid ultrasound performed within 30 days of randomization. Patients with carotid plaques (defined by Mannheim consensus criteria) will be classified as very high CV risk and initiated on high-intensity statin therapy (LDL target <55 mg/dL). Patients without plaques will be managed according to ESC 2021 guidelines.
  • Control group: standard management according to ESC 2021 guidelines throughout the study.

Randomization will be performed using REDCap, stratified by age, sex, classic CV risk factors, lipid-lowering treatment, rheumatic disease, and advanced therapy use.

Primary Endpoint:

Incidence of major adverse cardiovascular events (MACE), defined as: acute myocardial infarction or stroke, hospitalization for unstable angina, arterial revascularization for peripheral arterial disease, or CV death.

Secondary Endpoints:

  1. Efficacy of the strategy analyzed individually by rheumatic disease (RA, PsA, AxSpA)
  2. Comparison of efficacy between men and women
  3. Safety comparison of adverse events between groups

Follow-up:

All patients will be followed for 48 months. Patients on lipid-lowering treatment will have monthly visits during the intensification phase (maximum 5 visits) until therapeutic target is achieved, followed by semi-annual visits until month 48. Patients not requiring lipid-lowering treatment will have semi-annual visits throughout.

Statistical Analysis:

The primary analysis will follow an intention-to-treat approach. Cox regression models will be used to calculate Hazard Ratios with 95% confidence intervals, adjusted for relevant covariates. Kaplan-Meier survival curves will be compared using the log-rank test. A sample size of 1,944 patients provides 80% power to detect a 50% reduction in CV events in the experimental group (alpha=0.05). An interim analysis will be performed at 50% of expected events using the O'Brien-Fleming stopping rule, reviewed by an independent Data Safety Monitoring Board (DSMB).

Type d'étude

Interventionnel

Inscription (Estimé)

1944

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Espagne
    • Alicante
      • Alicante, Alicante, Espagne
      • Elche, Alicante, Espagne
      • Orihuela, Alicante, Espagne
        • Recrutement
        • Hospital Vega Baja de Orihuela
        • Contact:
    • Barcelona
      • Barcelona, Barcelona, Espagne
    • Cantabria
      • Laredo, Cantabria, Espagne
      • Santander, Cantabria, Espagne
        • Pas encore de recrutement
        • Hospital Universitario Marqués de Valdecilla
        • Contact:
      • Torrelavega, Cantabria, Espagne
    • Ciudad Real
      • Ciudad Real, Ciudad Real, Espagne
        • Pas encore de recrutement
        • Hospital General Universitario de Ciudad Real
        • Contact:
    • Córdoba
      • Córdoba, Córdoba, Espagne
        • Pas encore de recrutement
        • Hospital Universitario Reina Sofia
        • Contact:
    • Isla Baleares
      • Palma, Isla Baleares, Espagne
        • Pas encore de recrutement
        • Hospital Universitari Son Llàtzer
        • Contact:
    • Las Palmas
      • Las Palmas de Gran Canaria, Las Palmas, Espagne
        • Pas encore de recrutement
        • Hospital Universitario de Gran Canaria Dr. Negrín
        • Contact:
    • Madrid
      • Madrid, Madrid, Espagne
      • Madrid, Madrid, Espagne
        • Pas encore de recrutement
        • Hospital Universitario Ramon y Cajal
        • Contact:
    • Murcia
      • Murcia, Murcia, Espagne
        • Pas encore de recrutement
        • Hispital Universitario Virgen de la Arrixaca
        • Contact:
    • Santa Cruz de Tenerife
      • San Cristóbal de La Laguna, Santa Cruz de Tenerife, Espagne
        • Pas encore de recrutement
        • Hospital Universitario de Canarias
        • Contact:
    • Vizcaya
      • Bilbao, Vizcaya, Espagne
        • Recrutement
        • Hospital Universitario de Basurto
        • Contact:
    • Álava
      • Vitoria-Gasteiz, Álava, Espagne
        • Recrutement
        • Hospital Universitario Araba
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  1. Patients aged ≥50 years who have provided written informed consent.

  2. Fulfillment of classification criteria for at least one of the following inflammatory rheumatic diseases:

    • Rheumatoid arthritis (RA) according to ACR/EULAR 2010 criteria
    • Psoriatic arthritis (PsA) according to CASPAR criteria
    • Axial spondyloarthritis (AxSpA) according to ASAS criteria
    • Systemic lupus erythematosus (SLE) according to ACR/EULAR 2019 criteria
  3. Low-to-moderate cardiovascular risk according to SCORE2/OP classification.

Exclusion Criteria:

  1. Presence of previous cardiovascular events, type 2 diabetes mellitus, familial hypercholesterolemia, or chronic kidney disease resulting in classification as high or very high cardiovascular risk.
  2. Prior carotid ultrasound examination with subsequent therapeutic intervention derived from its results, either in the context of a research study or routine clinical practice.
  3. Contraindications to lipid-lowering therapy, including recent history of alcoholism, active liver disease, or unexplained and persistent elevation of serum transaminases exceeding three times the upper limit of normal (applicable to statins and ezetimibe).

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Experimental Group: Carotid Ultrasound
Patients undergo carotid ultrasound within 30 days of randomization. Patients with carotid plaques are reclassified as very high cardiovascular risk and initiated on high-intensity statin therapy (LDL target < 55 mg/dL). Patients without carotid plaques are managed according to ESC 2021 guidelines.
Test diagnostique: Carotid Ultrasound
Carotid ultrasound performed to detect subclinical atherosclerosis (carotid plaques) according to Manheim consensus criteria. The presence of carotid plaques triggers reclassification to very high cardiovascular risk and initiation of high-intensity lipid-loqering therapy
Médicament: High-intensity lipid-lowering therapy
Sequential lipid-lowering therapy initiated in experimental group patinets with carotid plaques, targeting LDL < 55 mg/dL. Treatment includes high-intensity statins (atorvastatin 40-80mg, rouvastatin 20-40mg), with possible addition of azetimibe, bempedoic acid, and/or PCSK9 inhibitors if target is not achieved.
Comparateur actif: Control Group: Standard Care
Patients are managed according to standard ESC 2021 cardiovascular prevention guidelines throughout the study, without carotid ultrasound assessment.
Autre: Standard care according to ESC 2021 guidelines
Lipid-lowerin treatment indicated and managed according to ESC 2021 cardiovascular prevention guidelines, based on SCORE/OP risk stratification, without carotid ultrasound assessment

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Incidence of Major Adverse Cardiovascular Events (MACE)
Délai: 48 months
48 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Participants Experiencing an Acute Myocardial Infarction or Stroke
Délai: 48 months
Incidence of acute myocardial infarction or stroke during the follow-up period.
48 months
Number of Participants Hospitalized for Unstable Angina
Délai: 48 months
Incidence of hospital admissions due to unstable angina during the follow-up period.
48 months
Number of Participants Requiring Arterial Revascularization for Peripheral Arterial Disease
Délai: 48 months
Incidence of arterial revascularization procedures required for peripheral arterial disease during the follow-up period.
48 months
Number of Participants Experiencing Cardiovascular Death
Délai: 48 months
Incidence of cardiovascular death during the follow-up period.
48 months
Number of Participants Experiencing a Major Cardiovascular Event. Stratified by Rheumatic Disease Subgroup
Délai: 48 months
Evaluation of the incidence of major cardiovascular events (acute myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization for peripheral artery disease, or cardiovascular death) analyzed individually for each included inflammatory disease (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and systemic lupus erythematosus).
48 months
Number of Participants Experiencing a Major Cardiovascular Event. Analyzed by Sex
Délai: 48 months
This measure evaluates the efficacy of the strategy by comparing the incidence of individual cardiovascular events (acute myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization or cardiovascular death) between male and female participants.
48 months
Incidence of adverse events
Délai: 48 months
48 months
LDL cholesterol levels
Délai: 48 months
48 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Instituto de Investigación Marqués de Valdecilla

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

22 avril 2026

Achèvement primaire (Estimé)

22 avril 2031

Achèvement de l'étude (Estimé)

1 décembre 2031

Dates d'inscription aux études

Première soumission

14 mai 2026

Première soumission répondant aux critères de contrôle qualité

20 mai 2026

Première publication (Réel)

28 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

28 mai 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

20 mai 2026

Dernière vérification

1 mai 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • PREVENER
  • 2025-521086-28-00 (Ctis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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