The Effect of Early Administration of PCSK9 Inhibitor to Acute Ischemic Stroke Patients Associated With Atherosclerosis on the Stroke Prognosis and Lipid Profile

Sponsor

Sun U. Kwon (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06083961

Collaborator

(none)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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

the change in lipid profile compared to baseline results
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.

Condition or Disease	Intervention/Treatment	Phase
Stroke, Acute Ischemic PCSK9 Inhibitor	Drug: Alirocumab	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single center study, Registry based, Pragmatic, Prospective trialSingle center study, Registry based, Pragmatic, Prospective trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 15, 2023

Anticipated Primary Completion Date :

Oct 15, 2026

Anticipated Study Completion Date :

Nov 15, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alirocumab The treatment group patients will receive an additional PCSK9 inhibitor (alirocumab 300mg once) at emergency departement in addition to statin therapy, which is conventional medication given for acute ischemic stroke.	Drug: Alirocumab Initial alirocumab, single dose of 300mg, subcutaneous injection Other Names: Praluent
No Intervention: Standard of care The control group patients will receive standard and conventional acute ischemic stroke treatment, which includes statin therapy.

Arm

Intervention/Treatment

Experimental: Alirocumab

The treatment group patients will receive an additional PCSK9 inhibitor (alirocumab 300mg once) at emergency departement in addition to statin therapy, which is conventional medication given for acute ischemic stroke.

Drug: Alirocumab

Initial alirocumab, single dose of 300mg, subcutaneous injection

Other Names:

Praluent

No Intervention: Standard of care

The control group patients will receive standard and conventional acute ischemic stroke treatment, which includes statin therapy.

Outcome Measures

Primary Outcome Measures

LDL change rate [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).]
The change rate of LDL in PCSK9 inhibitor treated group (alirocumab group) compared to standard of care group.
Achievement rate to target LDL level [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).]
The investigators intend to use 3 different criteria - LDL under 70mg/dl LDL under 55mg/dL LDL decrement over 50% compared to baseline (day0 LDL)

Secondary Outcome Measures

Change of total cholesterol(TC) [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).]
The change of TC during admission and at Outpatient department(OPD) follow up
Change triglyceridTG) [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).]
The change of TG during admission and at Outpatient department(OPD) follow up
Change of High density lipoprotein(HDL) [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).]
The change of HDL during admission and at Outpatient department(OPD) follow up
Change of Apolipoprotein-B [Apolipoprotein-B is collected at day-1, once.]
The change of Apolipoprotein-B during admission and at Outpatient department(OPD) follow up
Change of Lipoprotein-A [Lipoprotein-A are collected at day-1, once.]
The change of Lipoprotein-A during admission and at Outpatient department(OPD) follow up
The patient's outcome - 1 [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).]
Patients' modified Rankin score (mRS) at discharge date and Outpatient department(OPD) follow up date. mRS score ranges from 0 to 6, in which 0 means having no symptoms and 6 means expired.
The patient's outcome - 2 [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).]
Patients' National Institutes of Health Stroke Scale (NIHSS) score at discharge date and Outpatient department(OPD) follow up date. NIHSS ranges from 0 to maximum 42, in which 0 means having no symptoms.
The difference between admission and discharge - 1 [mRS is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).]
The difference between modified Rankin Scale (mRS) at admission and discharge state. The difference are then calculated to see whether the patients' status have improved or worsened. mRS score ranges from 0 to 6, in which 0 means having no symptoms and 6 means expired.
The difference between admission and discharge - 2 [NIHSS score is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).]
The difference between National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge state. The difference are then calculated to see whether the patients' status have improved or worsened. NIHSS ranges from 0 to maximum 42, in which 0 means having no symptoms.
Early neurological deterioration [The drop of NIHSS score in initial period (72 hours) during admission.]
Whether the National Institutes of Health Stroke Scale (NIHSS) score of the patient drops by 2 or more. NIHSS ranges from 0 to maximum 42, in which 0 means having no symptoms.
The expansion of stroke lesion [The follow up MRI is routinely taken at day-1 or day-2 of hospitalization.]
The increasement of size and territories of infarction, or hemorrhagic transformation at follow up MRI.
The recurrence rate [The event rate until the outpatient follow up date (up to 1 month, day-30).]
The rate of cardiovascular / cerebrovascular events during the follow up period
The rate of complications of statin - 1 [Laboratory tests for hemoglobin A1c (%) will be done at outpatient follow up date (day-30).]
The rate of complications or side effects by checking hemoglobin A1c.
The rate of complications of statin - 2 [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).]
The rate of complications or side effects by checking Liver function test (LFT) along with presence of symptoms.
The rate of complications of statin - 3 [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).]
The rate of complications or side effects by checking Liver function test (LFT) along with presence of symptoms.
The rate of complications of statin -4 [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).]
The rate of complications or side effects by checking muscle enzyme lab along with presence of symptoms.
The rate of complications of statin -5 [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).]
The rate of complications or side effects by checking muscle enzyme lab along with presence of symptoms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asan Medical Center	Seoul		Korea, Republic of	138-736

Sponsors and Collaborators

Sun U. Kwon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Sun U. Kwon, Professor, Asan Medical Center

ClinicalTrials.gov Identifier:

NCT06083961

Other Study ID Numbers:

PCSK9_001

First Posted:

Oct 16, 2023

Last Update Posted:

Oct 16, 2023

Last Verified:

Oct 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 16, 2023