Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes

Carotid Artery Stenosis Clinical Trial

— STANCE  

Official title:

Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02850081
• Other study ID #: AAAM2407
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2017
• Est. completion date: February 23, 2022

Study information

• Verified date: November 2022
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that pre-operative statin use is neuroprotective at maximal doses. The goals are to determine the safety, feasibility, and efficacy of maximizing statin doses for two weeks (12-18 days) prior to CEA using change in performance on a battery neuropsychometric tests as outcome measure. Study will recruit patients based on their preexisting statin regimen.

The investigators hypothesize that in asymptomatic CEA patients: 1) Pre-operative statin use is neuroprotective against early cognitive dysfunction (eCD) and lowers the risk of early mortality. 2) Maximal doses may be essential in achieving optimal neuroprotection against eCD.

Description:

Carotid endarterectomy (CEA) is a common surgery performed to reduce the risk of stroke in patients with carotid artery narrowing. Statins, a class of drugs usually used to lower blood cholesterol, may protect the brain after surgery. Specific statins have been shown to protect the brain after surgery when compared to others. eCD affects about 25% of patients undergoing CEA and about 15% of undergoing asymptomatic CEA. It is associated with marked elevations in tissue markers of cerebral injury and is associated with earlier post-CEA mortality. This clinically significant, but subtle, cerebral injury is 10 times more common than stroke and its mechanism appears to be similarly related to regional hypoperfusion and ischemia. It is imperative to determine in a prospective randomized trial whether alteration/increase of preoperative statin regimens leads to improved neurologic outcome and an even lower incidence of stroke and possibly greater survival.

In order to optimally design and conduct such a trial it is critical to: 1) explore the safety and feasibility of altering statin regimen acutely (approximately 2 weeks) before CEA, and 2) clearly establish the neuroprotective outcome of an acute alteration in statin regimen. This would promote a better understanding of statin neuroprotection in humans and determine the statin treatment that affords the most neuroprotection in patients undergoing one of the most commonly performed procedures in the US.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: February 23, 2022
• Est. primary completion date: February 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years of age.

2. Patient is currently on atorvastatin or simvastatin or rosuvastatin or statin naïve (no statins in the last 30 days).

3. The patient has unilateral or bilateral carotid artery stenosis that is considered severe (carotid artery diameter reduction = 70%) as defined by:

1. Peak systolic velocity of at least 230 cm/s plus at least one of these:

2. End diastolic velocity = 100 cm/s OR

3. CTA showing = 70% stenosis OR

4. MRA showing = 70% stenosis

4. This stenosis has not caused any stroke, transient cerebral ischemia, or other relevant neurological symptoms in the past.

5. The patient's attending doctor(s) (PMD, cardiologist, vascular/neurosurgeon) AND the patient have decided to proceed with a CEA to treat the patient's severe carotid stenosis.

6. The patient has no known circumstance or condition likely to preclude 1 year follow-up or adherence to the study protocol.

7. The patient is independent in their Activities of Daily Living at baseline.

8. Patient has the ability to provide informed consent.

Exclusion Criteria:

1. Patient has underlying disease other than atherosclerosis (i.e. autoimmune disease, known active malignancy).

2. Patient has documented dementia or screens out based on abnormal Baseline MoCA (=25) and AD8 (=2).

3. Patient's life expectancy is < 12 months.

4. Patient has advanced renal failure (serum creatinine > 2.5 mg/dL)

5. Patient has evidence of severe congestive heart failure or has history of end-stage cardiovascular disease (e.g. CHF NYHA Class III or IV or unstable angina).

6. Patient has history of intolerance or allergic reaction to any statins (myotoxicity, hepatic dysfunction, rash, etc.)

7. Patient has received an investigational drug within 30 days.

8. Patient is pregnant or lactating.

9. Patient is currently taking any of the following which have been shown to interact with atorvastatin and/or simvastatin and/or rosuvastatin (as per current drug package inserts):

• Cyclosporine;

• HIV Protease Inhibitors/Antivirals (e.g. rotanavir or plus rotanavir, tipranavir, lopinavir, boceprevir, saquinovir, darunavir, fosamprenavir, nelfinavir, efavirenz/tenofobir, atazanavir, simeprevir);

• Hep C Protease Inhibitor/Antivirals (e.g. telapravir);

• Antibiotics (i.e. cobicistat-containing products like Tybost, rifampin/rifampicin, clarithromycin, telithromycin, erythromycin);

• Anti-fungals (i.e. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole); *Gemfibrozil; Other Fenofibrates (e.g. Tricor, fibric acid);

• Niacin > 1g/day or statins in combination with niacin (e.g. Vytorin, Simcor);

• Colchicine;

• Danazol;

• Calcium Channel Blockers: Diltiazem, Varapamil;

• Dronedarone;

• Amiodarone;

• Digoxin;

• Ranolazine;

• Nefazodone;

• Warfarin/Coumadin;

• Lomitapide;

• Grapefruit juice > 1.2 liters/day (40.5 ounces/day).

Related Conditions & MeSH terms

• Carotid Artery Stenosis
• Carotid Stenosis
• Strokes

Intervention

Drug:
• Statin
Standard of care treatment (one of four): Simvastatin (to 40mg without amlodipine) Simvastatin (to 20 mg if currently on amlodipine) Atorvastatin (to 80mg) Rosuvastatin (to 20mg)
• Atorvastatin
A lipid-lowering agent and for prevention of events associated with cardiovascular disease. 10 mg or 80 mg capsules

Other:
• Placebo
A placebo pill will be used for patients that are to maintain their current dose of statins prior to their CEA.

Locations

Country	Name	City	State
United States	Albany Medical College/The Vascular Group at Albany	Albany	New York
United States	State University of New York at Buffalo	Buffalo	New York
United States	Columbia University Medical Center	New York	New York
United States	Cornell University Medical College (Weill)	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	New York University School of Medicine	New York	New York
United States	Valley Hospital	Ridgewood	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of eCD	Neurocognitive assessments =2SD worse than reference group in two or more cognitive domains or (b) =1.5SD worse than the reference group in all cognitive domains.	30 Days: 1) Pre-op vs. Post-CEA Day 1 (12-25 hrs post-op) and 2) Pre-op vs. Post-CEA Day 30
Secondary	Prevalence of early mortality	Data will be collected by follow up phone call	1 year