Trial of PCSK9 Inhibition in Patients With Acute Stroke and Symptomatic Intracranial Atherosclerosis (TOPICAL-MRI)

September 5, 2023 updated by: Chang Gung Memorial Hospital

Trial of PCSK9 Inhibition in Patients With Acute Stroke and Symptomatic Intracranial Atherosclerosis - a Prospective, Randomized, Open-label, Blinded End-point Study With High-resolution MR Vessel Wall Imaging

This study will evaluate whether low-density lipoprotein (LDL-C) lowering with alirocumab results in greater change from baseline in intracranial atherosclerotic plaque at week 26 than control in adults with acute ischemic stroke from intracranial atherosclerosis taking lipid lowering therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this trial, we will conduct a prospective, randomized, open-label, blinded end-point study using high-resolution MRI in patients with acute ischemic stroke from intracranial atherosclerosis to evaluate the efficacy and safety of alirocumab. We hypothesis that additional alirocumab treatment on a background of statin therapy could result in greater stabilization of intracranial plaque and regression of arterial stenosis.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

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

20 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical diagnosis of ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score of 1-15
  • Ischemic lesions on diffuse-weighted imaging located in the territory of symptomatic intracranial atherosclerosis (ICAS).
  • Symptomatic ICAS (above 30%) at the M1 or M2 of the middle cerebral artery, basilar artery or at the intracranial portion of the internal carotid artery or vertebral artery.
  • Serum LDL-C ≥70 mg/dL for subjects on lipid-lowering therapies (such as a statin and/or ezetimibe) or LDL-C ≥100 mg/dL for subjects without lipid-lowering therapies.
  • Ability to randomize within 7 days of time last known free of new ischemic symptoms.
  • Ability to receive alirocumab or statin treatment within 7 days of stroke onset.
  • Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
  • Pre-stroke modified Rankin Scale (mRS)≦2

Exclusion Criteria:

  • Age <20 years.
  • Judged by clinical physician.
  • After endovascular intervention or endarterectomy for the symptomatic ICAS.
  • Patients with more than 50% stenosis of extra-cranial arteries the relevant arteries on magnetic resonance angiography (MRA), including extra-cranial carotid artery or vertebral arteries.
  • Patients with high risk of cardioembolic source, such as atrial fibrillation, acute myocardial infarction, severe heart failure or valvular heart disease.
  • Other determined stroke etiology, such as vasculitis, shock, antiphospholipid antibody syndrome, arterial dissection, CADASIL and etc.
  • Qualifying ischemic event induced by angiography or surgery.
  • Severe non-cardiovascular comorbidity with life expectancy <6 months.
  • Contraindication or allergy to alirocumab or Gadolinium
  • Severe renal (serum creatinine >2 mg/dL) or calculated glomerular filtration rate <30 mL/min/ 1.73 m2 by estimated glomerular filtration rate (eGFR) using Cockcroft Gault methodology.
  • Hepatic insufficiency (INR>1.2; ALT>40 U/L or any resultant complication, such as variceal bleeding, encephalopathy, or jaundice)
  • Hemostatic disorder or systemic bleeding in the past 3 months
  • Current thrombocytopenia (platelet count <100 x109/L) or leukopenia (<2 x109/L)
  • Anemia（<10 mg/dL）
  • History of drug-induced hematologic or hepatic abnormalities
  • History of malignancy that required surgery, radiation therapy or systemic therapy.
  • Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use effective contraception.
  • Other neurological conditions that would complicate assessment of outcomes during follow-up.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intervention group
In addition to high-intensity statin and antiplatelet treatment, patients will receive treatment of alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks
Drug: Alirocumab
Alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks.
Other Names:
  • Praluent
No Intervention: Control group
Patient will have high-intensity statin and antiplatelet treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The changes of intracranial atherosclerotic plaque: stenosis degree
Time Frame: 26 weeks

The changes of intracranial atherosclerotic plaque in vessel-wall MRI before and after 6-month treatment, measured as stenosis degree.

The degree of stenosis was calculated as: (1-lumen area of stenotic lesion/reference lumen area)×100%.
26 weeks
The changes of intracranial atherosclerotic plaque: percent atheroma volume
Time Frame: 26 weeks

The changes of intracranial atherosclerotic plaque in vessel-wall MRI before and after 6-month treatment, measured as percent atheroma volume (PAV).

The PAV was calculated using the following equation:

PAV = Σ(EEM area - Lumen area) / ΣEEM area × 100, where EEM area is the cross-sectional area of the external elastic membrane and Lumen area is the cross-sectional area of the lumen.
26 weeks
The changes of intracranial atherosclerotic plaque: enhancement volume
Time Frame: 26 weeks

The changes of intracranial atherosclerotic plaque in vessel-wall MRI before and after 6-month treatment, measured as enhancement volume.

The enhancement volume was measured as post-contrast plaque enhancement for intracranial arteries and intraplaque hemorrhage.
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with major cardiovascular events
Time Frame: 26 weeks
Defined as the composite of cardiovascular death, myocardial infarction, transient ischemic attack, ischemic stroke and hemorrhagic stroke.
26 weeks
Percentage of patients with myocardial infarction
Time Frame: 26 weeks
patients with myocardial infarction
26 weeks
Percentage of patients with cardiovascular death
Time Frame: 26 weeks
patients with cardiovascular death
26 weeks
Percentage of patients with stroke
Time Frame: 26 weeks
Include transient ischemic attack, ischemic and hemorrhagic stroke
26 weeks
Percentage of patients with ischemic stroke or transient ischemic attack.
Time Frame: 26 weeks
Percentage of patients with ischemic stroke or transient ischemic attack.
26 weeks
Percentage of patients with new ischemic lesions
Time Frame: 26 weeks
Defined as new ischemic lesions in the territory of ICAS between 2 MRIs
26 weeks
Percentage of patients with favorable functional recovery
Time Frame: 3 months
Defined as a mRS ≦2 mRS. The Modified Rankin Scale (mRS) runs from 0-6, running from perfect health without symptoms(score 0) to death(score 6).
3 months
Changes in serum biomarkers
Time Frame: 26 weeks
Include liver function tests, HbA1c and lipid profiles.
26 weeks

Collaborators and Investigators

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

Sponsor

Chang Gung Memorial Hospital

Collaborators

Chang Gung University

Investigators

  • Study Director: Yenchu Huang, MD, Chang Gung Memorial Hospital, Chiayi

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 (Actual)

August 1, 2021

Primary Completion (Estimated)

August 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

July 22, 2021

First Submitted That Met QC Criteria

August 9, 2021

First Posted (Actual)

August 12, 2021

Study Record Updates

Last Update Posted (Actual)

September 6, 2023

Last Update Submitted That Met QC Criteria

September 5, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TOPICAL-MRI
  • MOST 110-2314-B-182A-072 (Other Grant/Funding Number: Ministry of Science and Technology, Taiwan)

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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