Carotid Ultrasound-Based Strategy for Primary Prevention of Cardiovascular Events in Inflammatory Rheumatic Disease (PREVENER) (PREVENER)
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.
연구 개요
상태
상세 설명
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:
- Efficacy of the strategy analyzed individually by rheumatic disease (RA, PsA, AxSpA)
- Comparison of efficacy between men and women
- 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).
연구 유형
등록 (추정된)
단계
- 4단계
연락처 및 위치
연구 장소
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Alicante
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Alicante, Alicante, 스페인
- 모병
- Hospital General Universitario de Alicante
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연락하다:
- Cristina Fenandez Carballido
- 이메일: soficarballido@hotmail.com
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Elche, Alicante, 스페인
- 아직 모집하지 않음
- Hospital Universitario de Elche
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연락하다:
- Cynthia Romera Lopez
- 이메일: CYNTHIA.ROMERA.LOPEZ@hotmail.com
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Orihuela, Alicante, 스페인
- 모병
- Hospital Vega Baja de Orihuela
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연락하다:
- Maria Paz Martinez Vidal
- 이메일: mpmavidal@yahoo.es
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Barcelona
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Barcelona, Barcelona, 스페인
- 모병
- Hospital Universitario Vall d'Hebron
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연락하다:
- Alba Erra Duran
- 이메일: alba.erra@vallhebron.cat
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Cantabria
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Laredo, Cantabria, 스페인
- 모병
- Hospital de Laredo
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연락하다:
- Cristina Corrales
- 이메일: c.corrales.selaya@gmail.com
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Santander, Cantabria, 스페인
- 아직 모집하지 않음
- Hospital Universitario Marqués de Valdecilla
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연락하다:
- Vanesa Calvo Rio
- 이메일: vcalvorio@gmail.com
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Torrelavega, Cantabria, 스페인
- 모병
- Hospital Sierrallana
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연락하다:
- Javier Rueda Gotor
- 이메일: ruedagotor@gmail.com
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Ciudad Real
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Ciudad Real, Ciudad Real, 스페인
- 아직 모집하지 않음
- Hospital General Universitario de Ciudad Real
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연락하다:
- David Castro Corredor
- 이메일: d.castrocorredor@gmail.com
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Córdoba
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Córdoba, Córdoba, 스페인
- 아직 모집하지 않음
- Hospital Universitario Reina Sofia
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연락하다:
- Maria Angeles Puche Larrubia
- 이메일: mangeles.puche@gmail.com
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Isla Baleares
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Palma, Isla Baleares, 스페인
- 아직 모집하지 않음
- Hospital Universitari Son Llàtzer
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연락하다:
- Inmaculada Ros Vilamajóv
- 이메일: iros@hsll.es
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Las Palmas
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Las Palmas de Gran Canaria, Las Palmas, 스페인
- 아직 모집하지 않음
- Hospital Universitario de Gran Canaria Dr. Negrín
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연락하다:
- Ivan Ferraz Amaro
- 이메일: iferrazamaro@hotmail.com
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Madrid
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Madrid, Madrid, 스페인
- 아직 모집하지 않음
- Hospital Universitario La Paz
-
연락하다:
- Eugenio de Miguel Mendieta
- 이메일: eugenio.demiguel@gmail.com
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Madrid, Madrid, 스페인
- 아직 모집하지 않음
- Hospital Universitario Ramon y Cajal
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연락하다:
- Marta Valero Expósito
- 이메일: martavaleroex@yahoo.es
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Murcia
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Murcia, Murcia, 스페인
- 아직 모집하지 않음
- Hispital Universitario Virgen de la Arrixaca
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연락하다:
- Manuel Jose Moreno Ramos
- 이메일: mjmorenoramos@gmail.com
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Santa Cruz de Tenerife
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San Cristóbal de La Laguna, Santa Cruz de Tenerife, 스페인
- 아직 모집하지 않음
- Hospital Universitario de Canarias
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연락하다:
- Ivan Ferraz Amaro
- 이메일: iferrazamaro@hotmail.com
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Vizcaya
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Bilbao, Vizcaya, 스페인
- 모병
- Hospital Universitario de Basurto
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연락하다:
- Maria Luz Garcia Vivar
- 이메일: marilugv@hotmail.com
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Álava
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Vitoria-Gasteiz, Álava, 스페인
- 모병
- Hospital Universitario Araba
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연락하다:
- Jaime Calvo Allen
- 이메일: jcalvo@ser.es
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Patients aged ≥50 years who have provided written informed consent.
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
- Low-to-moderate cardiovascular risk according to SCORE2/OP classification.
Exclusion Criteria:
- 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.
- Prior carotid ultrasound examination with subsequent therapeutic intervention derived from its results, either in the context of a research study or routine clinical practice.
- 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).
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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.
|
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
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.
|
|
활성 비교기: Control Group: Standard Care
Patients are managed according to standard ESC 2021 cardiovascular prevention guidelines throughout the study, without carotid ultrasound assessment.
|
Lipid-lowerin treatment indicated and managed according to ESC 2021 cardiovascular prevention guidelines, based on SCORE/OP risk stratification, without carotid ultrasound assessment
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
|
Incidence of Major Adverse Cardiovascular Events (MACE)
기간: 48 months
|
48 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of Participants Experiencing an Acute Myocardial Infarction or Stroke
기간: 48 months
|
Incidence of acute myocardial infarction or stroke during the follow-up period.
|
48 months
|
|
Number of Participants Hospitalized for Unstable Angina
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 48 months
|
48 months
|
|
|
LDL cholesterol levels
기간: 48 months
|
48 months
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- PREVENER
- 2025-521086-28-00 (씨티스)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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