Clinical trial NCT06231966: Randomized Comparison of Efficacy and Safety of High-intensity Rosuvastatin/Ezetimibe Combination Versus Treat-to-target Rosuvastatin Monotherapy for Patients With Peripheral Artery or Polyvascular Disease (CARE-PVD Trial)
Official title: Randomized Comparison of Efficacy and Safety of High-intensity Rosuvastatin/Ezetimibe Combination Versus Treat-to-target Rosuvastatin Monotherapy for Patients With Peripheral Artery or Polyvascular Disease (CARE-PVD Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Artery Disease
Polyvascular Disease
Keywords: Peripheral artery disease
polyvascular disease
lipid lowering therapy
LDL cholesterol
Clinical outcomes
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2024-01-30
Enrollment: 2462
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with atherosclerotic peripheral artery disease often have combined coronary artery disease or cerebral artery disease and show high rates of cardiovascular mortality and morbidities. Therefore, secondary prevention for these patients is of great clinical importance. Currently, Korean, US, and European guidelines recommend different LDL cholesterol target goals in patients with peripheral artery disease. In recent clinical trials, combination therapy of statin plus ezetimibe demonstrated improved cardiovascular outcomes compared with statin monotherapy. Thus, the purpose of the CARE-PVD study is to investigate whether the combination therapy of high intensity rosuvastatin 20 mg plus ezetimibe 10 mg can improve cardiovascular outcomes in patient with peripheral artery disease or polyvascular artery disease in comparison with rosuvastatin treat-to-target (LDL cholesterol \<70 mg/dL) monotherapy.

Detailed description: * A multicenter prospective randomized controlled clinical trial
* A total of 2462 subjects with cperipheral artery disease or polyvascular disease will be included according to inclusion and exclusion criteria.
* Patients will be randomized in a 1:1 manner into the rosuvastatin/ezetimibe combination therapy group or rosuvastatin monotherapy group. • The randomization will be startified by previous use of statin and presence of diabetes mellitus. • In the rosuvastatin/ezetimibe combination therapy group, rosuvastatin 20 mg plus ezetimibe 10 mg will be administered. • In the rosuvastatin monotherapy group, rosuvastatin will be administered and the dose of rosuvastatin will be adjusted to attain the target LDL cholesterol level \< 70 mg/dL.
* Patients will be followed clinically for 3years.
* The primary endpoint is defined as the composite of Major cardiovascular event (MACE) or major adverse limb event (MALE) at 3-year follow-up.

Eligibility criteria: Inclusion criteria:

1. Ages 19-80
2. Patient with arteriosclerotic lower extremity artery disease or multivessel disease 1) Arteriosclerotic lower extremity artery disease: If any of the following applies

   * Ankle-brachial index \<0.85 with symptoms of intermittent claudication
   * Lower extremity artery stenosis of more than 50% on imaging tests
   * History of receiving interventional or surgical treatment for lower extremity artery disease) 2) Arteriosclerotic multivessel disease: When at least two of the following diseases exist even if there is no lower extremity artery disease
   * Coronary artery disease
   * History of carotid artery stenosis (more than 50%) or ischemic stroke/transient cerebral ischemia event
   * degenerative thoracic (maximum diameter \>4 cm) or abdominal (maximum diameter \>3cm) aortic aneurysm
3. Patients on medication for dyslipidemia or patients with LDL cholesterol level higher than the target level for peripheral arterial disease (≥70 mg/dL) and not on lipid lowering medication

Exclusion criteria:

1. Chronic limb threatening ischemia (Rutherford 4\~6)
2. History of acute coronary syndrome or stroke/TIA or lower extremity amputation within 6 months
3. Acute liver disease or persistent unexplained elevation of serum AST or ALT more than twice the upper limit of normal
4. Severe renal dysfunction (eGFR \<30 mL/min/1.73m2) or dependancy on dialysis
5. History of allergic or hypersensitivity reaction to statin or ezetimibe or side effects requiring discontinuation of lipid lowering therapy
6. Solid organ transplant recipients
7. Pregnant women, potentially pregnant or lactating women
8. Life expectancy of less than 3 years
9. When follow-up for more than 1 year is not possible
10. Inability to understand or read the consent form

Primary outcomes:
measure: Composite of Major cardiovascular event or major adverse limb event
timeFrame: at 3 years
Secondary outcomes:
measure: Major cardiovascular event(death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina or heart failure)
timeFrame: at 1, 2, and 3 years
measure: Major adverse limb event(acute lower extremity ischemia, major lower extremity amputation, and revascularization of lower extremity arteries)
timeFrame: at 1, 2, and 3 years
measure: discontinuation of lipid lowering therapy
timeFrame: at 1, 2, and 3 years
measure: adverse clinical events related to lipid lowering therapy
timeFrame: at 1, 2, and 3 years
measure: attainment of LDL cholesterol
timeFrame: at 1, 2, and 3 years
measure: Major cardiovascular event : non-fatal myocardial infarction
timeFrame: at 1, 2, and 3 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine
Study officials:
References: