Clinical trial NCT05976893: Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer
Official title: Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: ASCVD
Atherosclerotic Cardiovascular Disease
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor
Cancer
Keywords: ASCVD
cancer
PCSK9
Lead sponsor: Xinjiang Medical University
Sponsor class: OTHER
Collaborators: name: Xinjiang Medical University
First posted: 2023-08-04
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patients with very high risk of ASCVD and cancer
Primary purpose: TREATMENT

Brief summary: This study is a prospective, randomized, open-label, and single center trial. To evaluate the effect of treatment with PCSK9 inhibitor on the risk for cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, or coronary revascularization in patients with very high risk of atherosclerotic cardiovascular disease (ASCVD) and cancer.

Detailed description: Subjects will be randomly assigned in a 1:1 ratio to receive subcutaneous injections of PCSK9 inhibitor (evolocumab:420 mg every 4 weeks) plus moderate intensity statin therapy or the statin alone therapy. After randomization, patients will come to the hospital every 4 weeks to collect relevant laboratory results and clinical outcomes, and be detected by echocardiography and carotid ultrasound every 12 weeks until the end of follow-up at week 48 or the occurrence of an endpoint event. The entire study is expected to be conducted for 3 years, with a recruitment period of 2 years.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18 to ≤ 80 years of age
* Patients with very high risk of ASCVD (with any of the following):

  1. Documented ASCVD, either clinical or unequivocal on imaging. Documented ASCVD includes previous acute coronary syndrome (ACS), stable angina, coronary revascularization (percutaneous coronary intervention, coronary artery bypass graft, and other arterial revascularization procedures), stroke and transient ischemic attack (TIA), and peripheral arterial disease. Unequivocally documented ASCVD on imaging includes those findings that are known to be predictive of clinical events, such as significant plaque on coronary angiography or computed tomography (CT) scan (multivessel coronary disease with two major epicardial arteries having \>50% stenosis), or on carotid ultrasound.
  2. Diabetes mellitus (DM) with target organ damage, or at least three major risk factors, or early onset of type 1 diabetes mellitus (T1DM) of long duration (\>20 years).
* Patients have been diagnosed with cancer through histopathology and have a life expectancy of more than 1 year
* Fasting low-density lipoprotein cholesterol (LDL-C) ≥ 1.8 mmol/L or non-high-density lipoprotein cholesterol (non HDL-C) \> 2.6 mmol/L
* Participate voluntarily and sign an informed consent
* Negative serum Pregnancy test (in women with fertility potential)

Exclusion Criteria:

* Pregnant and lactating women
* During the study period and within 3 months of receiving the last dose of the study drug, women with fertility intentions and men unwilling to use effective contraceptive methods
* New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction \< 30%
* Uncontrolled hypertension, defined as systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg
* Plan for coronary revascularization or other cardiac surgery in recent (within 3 months after randomization)
* Severe renal insufficiency, defined as estimated glomerular filtration rate (eGRF) \< 30ml/min/1.73m2 or Serum creatinine (Scr) \> 221 umol/L
* Severe liver dysfunction, defined as an increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3 times above the upper limit of normal
* Have used PCSK9 inhibitors within 3 months before enrollment, or have a history of severe allergic reactions to PCSK9 inhibitors
* Severe infections requiring intravenous antibiotics
* HIV-positive or history of acquired immunodeficiency syndrome (AIDS)
* With cognitive impairment or psychiatric illnesses
* Participating in other trials

Primary outcomes:
measure: Major cardiovascular adverse events
timeFrame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
Secondary outcomes:
measure: All cause death
timeFrame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
measure: Composite end points
timeFrame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
measure: The compliance rate of lipid control
timeFrame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
measure: The changes of carotid plaque
timeFrame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
Other outcomes:
Locations:
Study officials:
affiliation: First Affiliated Hospital of Xinjiang Medical University
name: Xiang Xie, PhD
role: PRINCIPAL_INVESTIGATOR
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