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

October 9, 2023 updated by: Sun U. Kwon

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LDL change rate
Time Frame: 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.
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).
Achievement rate to target LDL level
Time Frame: 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 -

  1. LDL under 70mg/dl
  2. LDL under 55mg/dL
  3. LDL decrement over 50% compared to baseline (day0 LDL)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of total cholesterol(TC)
Time Frame: 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
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).
Change triglyceridTG)
Time Frame: 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
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).
Change of High density lipoprotein(HDL)
Time Frame: 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
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).
Change of Apolipoprotein-B
Time Frame: Apolipoprotein-B is collected at day-1, once.
The change of Apolipoprotein-B during admission and at Outpatient department(OPD) follow up
Apolipoprotein-B is collected at day-1, once.
Change of Lipoprotein-A
Time Frame: Lipoprotein-A are collected at day-1, once.
The change of Lipoprotein-A during admission and at Outpatient department(OPD) follow up
Lipoprotein-A are collected at day-1, once.
The patient's outcome - 1
Time Frame: 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.
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).
The patient's outcome - 2
Time Frame: 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.
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).
The difference between admission and discharge - 1
Time Frame: 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.
mRS is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).
The difference between admission and discharge - 2
Time Frame: 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.
NIHSS score is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).
Early neurological deterioration
Time Frame: 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 drop of NIHSS score in initial period (72 hours) during admission.
The expansion of stroke lesion
Time Frame: 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 follow up MRI is routinely taken at day-1 or day-2 of hospitalization.
The recurrence rate
Time Frame: 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 event rate until the outpatient follow up date (up to 1 month, day-30).
The rate of complications of statin - 1
Time Frame: 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.
Laboratory tests for hemoglobin A1c (%) will be done at outpatient follow up date (day-30).
The rate of complications of statin - 2
Time Frame: 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.
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 of statin - 3
Time Frame: 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.
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 of statin -4
Time Frame: 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.
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 of statin -5
Time Frame: 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.
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun U. Kwon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 15, 2023

Primary Completion (Estimated)

October 15, 2026

Study Completion (Estimated)

November 15, 2026

Study Registration Dates

First Submitted

September 12, 2023

First Submitted That Met QC Criteria

October 9, 2023

First Posted (Actual)

October 16, 2023

Study Record Updates

Last Update Posted (Actual)

October 16, 2023

Last Update Submitted That Met QC Criteria

October 9, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCSK9_001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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