Carotid Stenosis
Conditions
Keywords
Patients scheduled for elective carotid endarterectomy
Brief summary
To evaluate the causal relationship between Rho/Rho kinase overactivity and mechanisms of vascular dysfunction in patients with atherosclerosis.
Interventions
Fasudil 40 mg three times a day x 14 days
DRUGPlacebo Oral Tablet
Placebo oral tablet manufactured to mimic fasudil three times a day x 14 days
Sponsors
Doris Duke Charitable Foundation
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, placebo controlled, parallel arm design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with \>= 70% carotid stenosis (unilateral or bilateral) who are scheduled to undergo elective carotid endarterectomy * Age \>= 18 years * Agreement of the operating surgeon for patient to participate
Exclusion criteria
* Surgery scheduled \< 14 days after randomization * Pregnancy * ALT, GGT \> 3x upper limit of normal (ULN) * Creatinine \> 3.5 mg/dL * Prior intolerance to statins * Reluctance to add or change dosage of statin therapy during study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Rho/ROCK Expression With Concordant Increase in eNOS Expression/Activity in Carotid Specimens. | >= 2 weeks | We were going to compare Rho/ROCK expression and eNOS expression/activity in carotid specimens obtained from patients treated with fasudil and compare those to specimens obtained from patients treated with placebo. We anticipated that Rho/ROCK expression and activity would be decreased in spcimens obtained from fasudil treated patients compared to specimens obtained from patients treated with placebo. We also anticipated that eNOS expression and activity would be increased in specimens obtained from patients treated with fasudil compared to specimens obtained from patients treated with placebo. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug: Fasudil Fasudil 40 mg three times a day X 14 days
Fasudil Hydrochloride: Fasudil 40 mg three times a day x 14 days | 2 |
| Drug: Placebo Placebo 1 tablet three times daily x 14 days
Placebo Oral Tablet: Placebo manufactured to mimic fasudil three times a day x 14 days | 0 |
| Total | 2 |
Baseline characteristics
| Characteristic | Drug: Fasudil | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants |
| Region of Enrollment United States | 2 participants | 2 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 0 |
| serious Total, serious adverse events | 0 / 2 | 0 / 0 |
Outcome results
Primary
Decrease in Rho/ROCK Expression With Concordant Increase in eNOS Expression/Activity in Carotid Specimens.
We were going to compare Rho/ROCK expression and eNOS expression/activity in carotid specimens obtained from patients treated with fasudil and compare those to specimens obtained from patients treated with placebo. We anticipated that Rho/ROCK expression and activity would be decreased in spcimens obtained from fasudil treated patients compared to specimens obtained from patients treated with placebo. We also anticipated that eNOS expression and activity would be increased in specimens obtained from patients treated with fasudil compared to specimens obtained from patients treated with placebo.
Time frame: >= 2 weeks
| Arm | Measure | Value |
|---|---|---|
| Drug: Fasudil Hydrochloride | Decrease in Rho/ROCK Expression With Concordant Increase in eNOS Expression/Activity in Carotid Specimens. | 0 |
| Drug: Placebo Oral Tablet | Decrease in Rho/ROCK Expression With Concordant Increase in eNOS Expression/Activity in Carotid Specimens. | 0 |