Clinical trial NCT06083961: The Effect of Early Administration of PCSK9 Inhibitor to Acute Ischemic Stroke Patients Associated With Atherosclerosis on the Stroke Prognosis and Lipid Profile
Official title: The Effect of Early Administration of PCSK9 Inhibitor, Alirocumab to Acute Ischemic Stroke Patients Associated With Atherosclerosis on the Stroke Prognosis and Lipid Profile, a Single Center Study, Registry Based, Pragmatic, Prospective Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Stroke, Acute Ischemic
PCSK9 Inhibitor
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2023-10-16
Enrollment: 200
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single center study, Registry based, Pragmatic, Prospective trial
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors) in acute ischemic stroke patients associated with atherosclerosis by investigating

1. the change in lipid profile compared to baseline results
2. the effects on prognosis of stroke The participants will be given PCSK9 inhibitor right after confirmation of acute ischemic stroke, and the investigators will compare the results to the control group, whom are acute ischemic stroke patients treated with conventional lipid lowering therapy, statin and/or ezetimibe.

Detailed description: This clinical trial will be recommended to patients aged 19 and older who are admitted with ischemic stroke accompanied by atherosclerosis of large arteries, rather than cardiac embolism. Upon confirmation of ischemic stroke through CT and MRI in the emergency room, the patient will be provided with a detailed explanation of the future treatment plan and the purpose of this study.

Depending on the day of the week, the patient will be randomly assigned to the treatment group (alirocumab + high-dose statin group) and the control group (high-dose statin group) in a 1:1 ratio.

For those in the treatment group, alirocumab (brand name: Praluent Pen) 300mg will be administered as a single dose. Both the treatment and control groups will receive standard diagnostic tests and treatments as conventional stroke patients unrelated to the clinical trial. Blood samples collected for testing will be promptly discarded by the hospital's diagnostic laboratory. Both groups will have outpatient visits one month after discharge.

The investigators are planning on total 200 patients enrollment (100 treatment group + 100 control group).

For categorical variables, frequency and percentage will be provided, and for continous variables, mean and standard deviation will be provided. All statistical tests used for analysis will be two-tailed. Statistical significance will be tested at a 5% significance level. If necessary, two-sided 95% confidence intervals will be provided.

In the analysis of the entire registered patient population, not only univariate analysis but also multivariate analysis (Cox proportional hazard regression model) will be conducted to adjust for other factors.

Detailed techniques for data summary and statistical analysis from the data collected in this clinical trial will be specified in the Statistical Analysis Plan (SAP).

When sided effects or adverse events occur, the Principal Investigator is required to promptly report safety information, which includes occurrences of serious adverse events and drug-related adverse reactions, to the Institutional Review Board (IRB) of the trial institution within the timeframe specified in the trial institution's standard operating procedures during the trial period. Upon becoming aware of all occurrences of serious adverse events and special situations, regardless of their causality with the investigational product, the Principal Investigator will complete a 'Serious Adverse Event Report/Adverse Event of Special Situation' within 24 hours.

Eligibility criteria: Inclusion Criteria:

* Non-cardioembolic Stroke
* Acute Ischemic stroke within 7 days of symptom onset (confirmed by CT or MRI)
* Age 19 and above
* Significant stenosis associated with atherosclerosis in major intracranial / extracranial vessels.
* National Institutes of Health Stroke Scale(NIHSS) score of 15 or less at admission
* Patients with the capacity to consent for participation in the clinical trial.

Exclusion Criteria:

* Presence of high-risk factors for cardioembolism
* Risk of ischemic stroke due to thrombosis from other causes
* Patients with hemorrhagic stroke, brain tumors, or brain abscesses
* Patients unable to take statins or PCSK9 inhibitors
* Pre-stroke mRS score of 3 or higher
* Severe liver failure (liver enzyme \> 3 times the upper normal limit) or renal failure (serum Creatinine \> 2mg/dL or estimated glomerular filtration rate \< 30 mL/min/1.73m2)
* Anemia (hemoglobin \< 8mg/dL) or thrombocytopenia (platelet count \< 100K)
* Uncontrolled diabetes not managed by medication or insulin
* Pregnant or breastfeeding patients
* Patients already receiving PCSK-9 inhibitors
* Patients deemed inappropriate for participation in the clinical trial by the investigator for other reasons.

Primary outcomes:
measure: LDL change rate
timeFrame: LDL level at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
measure: Achievement rate to target LDL level
timeFrame: LDL target achievement rate at day-1 of hospitalization, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
Secondary outcomes:
measure: Change of total cholesterol(TC)
timeFrame: TC levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
measure: Change triglyceridTG)
timeFrame: TG levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
measure: Change of High density lipoprotein(HDL)
timeFrame: HDL levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
measure: Change of Apolipoprotein-B
timeFrame: Apolipoprotein-B is collected at day-1, once.
measure: Change of Lipoprotein-A
timeFrame: Lipoprotein-A are collected at day-1, once.
measure: The patient's outcome - 1
timeFrame: mRS is calculated when patients are discharged from neurology department(normally day-5 to day-7), and when patients come to outpatient department (day-30).
measure: The patient's outcome - 2
timeFrame: NIHSS score is calculated when patients are discharged from neurology department(normally day-5 to day-7), and when patients come to outpatient department (day-30).
measure: The difference between admission and discharge - 1
timeFrame: mRS is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).
measure: The difference between admission and discharge - 2
timeFrame: NIHSS score is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).
measure: Early neurological deterioration
timeFrame: The drop of NIHSS score in initial period (72 hours) during admission.
measure: The expansion of stroke lesion
timeFrame: The follow up MRI is routinely taken at day-1 or day-2 of hospitalization.
measure: The recurrence rate
timeFrame: The event rate until the outpatient follow up date (up to 1 month, day-30).
measure: The rate of complications of statin - 1
timeFrame: Laboratory tests for hemoglobin A1c (%) will be done at outpatient follow up date (day-30).
measure: The rate of complications of statin - 2
timeFrame: Laboratory tests for alanine transaminase (ALT, IU/L) and investigations of possible complication symptoms (abdominal pain or tenderness, fatigue, nausea/vomiting, etc) will be done at outpatient follow up date (day-30).
measure: The rate of complications of statin - 3
timeFrame: Laboratory tests for aspartate transaminase (AST, IU/L) and investigations of possible complication symptoms (abdominal pain or tenderness, fatigue, nausea/vomiting, etc) will be done at outpatient follow up date (day-30).
measure: The rate of complications of statin -4
timeFrame: Laboratory tests (myoglobin, ng/mL) and investigations of possible complication symptoms (muscle pain or fatigue, tenderness) will be done at outpatient follow up date (day-30).
measure: The rate of complications of statin -5
timeFrame: Laboratory tests (creatine kinase, IU/L) and investigations of possible complication symptoms (muscle pain or fatigue, tenderness) will be done at outpatient follow up date (day-30).
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
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