Clinical trial NCT06134635: Short-term Effect of PCSK9 Inhibitor in Patients With Acute Ischemic Stroke
Official title: Short-term Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor in Chinese Population With Acute Ischemic Stroke: the Singe-center Real-world Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Acute Ischemic Stroke
Keywords: Acute Ischemic Stroke
Evolocumab
PCSK9 Inhibitor
Statins
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acute ischemic stroke patients aged 18 to 80 years

Brief summary: This is a prospective cohort study to investigate the early impact of evolocumab on patients with acute ischemic stroke (AIS) in China. Evolocumab, a proprotein convertase subtilisin/kexin taye 9 inhibitor, can significantly reduce low density lipoprotein cholesterol (LDL-C) levels and has a positive effect on improving cardiovascular events. However, existing studies have focused almost exclusively on the long-term effects of Evolocumab, and the early effects of Evolocumab on AIS patients remains unclear.

Detailed description: Patients aged 18-80 years old admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University, with a definite diagnosis of acute ischemic stroke and receiving lipid-lowering therapy with statins with or without evolocumab will be included in this study. Participants will be divided into two groups according to the lipid-lowering therapy they used: 1) statin-alone group: the participants receive statins alone (atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn) for lipid reduction, and 2) PCSK9-i group: the participants receive statins (atorvastatin 20mg qn or rosuvastatin 10mg qn or pivastatin 2mg qn) and evolocumab (140mg twice a month) for lipid reduction. Most importantly, the lipid-lowering therapy of participants will be decided only by clinicians not involved in the study, not by the investigators. The levels of blood lipid (TC, TG, HDL-C, LDL-C, Apo AI and Apo B) and inflammatory biomarkers (hsCRP and IL-6) of these participants at different time points (day 1, day 3, day 5, and month 3) will be recorded. The target level of LDL-C is the LDL-C reduction ≥50% from the baseline and LDL-C\<1.4mmol/L (55mg/dL). In addition, the cardiovascular events and adverse drug reactions of these participants during follow-up will also be recorded. During the follow-up period (3 months), participants who changed their lipid-lowering regimen, including the type, dosage and frequency of statins and evolocumab, will be excluded from the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with acute ischemic stroke;
* Aged 18-80 years, gender unlimited;
* The fasting LDL-C≥1.8mmol/L (70mg/dL);
* Received lipid-lowering therapy with statins with or without evolocumab;
* Premorbid mRS ≤ 2;
* NIHSS ≤ 15;
* Subjects participated in the study voluntarily and signed informed consent.

Exclusion Criteria:

* Participants who changed their lipid-lowering regimen;
* Participants allergic to PCSK9 inhibitors;
* Participants treated with cholesterol ester transfer protein inhibitor within 12 months prior to enrollment;
* LDL or plasma apheresis within 12 months prior to enrollment；
* Last known left ventricular ejection fraction \< 30%
* Known hemorrhagic stroke at any time；
* Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \< 20 mL/min/1.73m2 at final screening；
* Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times；
* Pregnant or lactating women；
* Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years.

Primary outcomes:
measure: LDL-C target achievement rate on Day 5, Month 3
timeFrame: Day 5, Month 3
Secondary outcomes:
measure: Percentage change in LDL-C level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in HDL-C level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in TC level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in TG level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in Apo AI level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in Apo B level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in hsCRP level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage change in IL-6 level on Day 1, Day 3, Day 5, and Month 3
timeFrame: Day 1, Day 3, Day 5, Month 3
measure: Percentage of mRS≤2 on Month 3
timeFrame: Month 3
measure: Incidence of major cardiovascular events on Month 3
timeFrame: Month 3
measure: Incidence of adverse events on Month 3
timeFrame: Month 3
Other outcomes:
Locations:
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Meng Ran, PhD
role: STUDY_CHAIR
References: