Ischemic Stroke
Conditions
Keywords
Intracranial Atherosclerosis
Brief summary
The purpose of this study will be to understand the underlying mechanism by which PCSK9 inhibition reduces the rate of ischemic stroke seen in the pivotal studies that led to its FDA approval for ASCVD such as ischemic stroke. Those trials (FOURIER and ODYSSEY) enrolled almost 50,000 patients and showed that PCSK9 inhibition therapy is safe and effective. The investigators hypothesize that PCSK9 inhibition lowers the rate of stroke by reducing atherosclerotic plaque, which would be particularly beneficial for patients with intracranial atherosclerosis, who have the highest rate of recurrent stroke of any stroke mechanism.
Interventions
DRUGRepatha
140 MG in 1 ML Prefilled Syringe PCSK9 Inhibitor
Sponsors
Amgen
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, ≥ 18 years of age * History of ischemic stroke, defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction (American Heart Association definition). * Large vessel atherosclerosis of an intracranial artery in the circle of Willis with 50-99% stenosis by WASID criteria (percent stenosis = (1-\[diameter stenosis/diameter normal\]) x 100%) on MRA, CTA or DSA \------ Eligible arteries: vertebral (V4), basilar, PCA (P1, P2), MCA (M1, M2), tICA, ACA (A1) * Current statin use or contraindication to statin * Fasting LDL-C ≥ 70 mg/dL or LDL-C ≥ 60 mg/dL if lipoprotein (a) \> 30 mg/ dL
Exclusion criteria
Gadolinium or PCSK9 inhibitor allergy * Acute or chronic kidney disease with eGFR\<30 ml/min/1.73m2 * Pacemaker or other MRI contraindications per American College of Radiology guidelines * Inability to return for 78 week follow-up clinic visit and vwMRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stenosis | 1.5 years | Measured on ToF MRA, CE-MRA, T1 Dante |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Atheroma Volume | 1.5 years | Measured on ToF MRA, CE-MRA, T1/T2/PD Dante |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ischemic Stroke | 1.5 years | Adjudicated |
| ITA | 1.5 years | Adjudicated |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Repatha Repatha: 140 MG in 1 ML Prefilled Syringe PCSK9 Inhibitor | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Intervention Repatha |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Stenosis
Measured on ToF MRA, CE-MRA, T1 Dante
Time frame: 1.5 years
Population: Outcome data were not collected due to early termination
Secondary
Percent Atheroma Volume
Measured on ToF MRA, CE-MRA, T1/T2/PD Dante
Time frame: 1.5 years
Population: Study funding was terminated before reaching the analysis phase of the study. No participants made it to 1.5 years. Outcome data were not collected due to early termination
Other Pre-specified
Ischemic Stroke
Adjudicated
Time frame: 1.5 years
Population: Study funding was terminated before reaching the analysis phase of the study. No participants made it to 1.5 years
Other Pre-specified
ITA
Adjudicated
Time frame: 1.5 years
Population: Study funding was terminated before reaching the analysis phase of the study. No participants made it to 1.5 years