Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes

NCT02850081 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: AAAM2407
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Carotid Artery Stenosis; Strokes

Keywords

Carotid endarterectomy; CEA; stroke; asymptomatic stenosis

Outcome Measures

Primary Outcomes (1)

• 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. Due to early study termination and limited sample size, the study was not adequately powered to support inferential statistical comparisons. Therefore, outcome data are presented descriptively without formal statistical testing.

  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 Outcomes (1)

• Prevalence of Early Mortality

  1 year

Study Arms (3)

Observational - Maximal Dose - ARM 1

NO INTERVENTION

Patients on a pre-existing maximal dose of either Simvastatin (40mg) with/without currently taking amlodipine (Norvasc) and those on Simvastatin 20mg while currently on amlodipine; Atorvastatin (80mg), or Rosuvastatin (20mg) regimen will be observed for \~2 weeks before their CEA.

Less Than Maximal Dose - ARM 2

EXPERIMENTAL

Patients on a pre-existing statin regimen at a lower dose (less than maximal) of Simvastatin \<40mg without amlodipine and \<20mg with amlodipine; Atorvastatin (\<80mg) or Rosuvastatin (\<20mg) will be randomized to maintain their current dose plus placebo or be increased to the maximal dose of their current statin for \~2 weeks before their CEA.

Drug: Statin; Other: Placebo

Statin Naive - ARM 3

EXPERIMENTAL

Patients on no pre-existing statin regimen will be randomized to Atorvastatin 10 mg or Atorvastatin 80 mg for \~2 weeks before their CEA

Drug: Atorvastatin

Interventions

Statin DRUG

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)

Also known as: Pre-existing statin regimen

Less Than Maximal Dose - ARM 2

Atorvastatin DRUG

A lipid-lowering agent and for prevention of events associated with cardiovascular disease. 10 mg or 80 mg capsules

Also known as: Lipitor

Statin Naive - ARM 3

Placebo OTHER

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

Also known as: Sugar pill

Less Than Maximal Dose - ARM 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years of age.
• Patient is currently on atorvastatin or simvastatin or rosuvastatin or statin naïve (no statins in the last 30 days).
• The patient has unilateral or bilateral carotid artery stenosis that is considered severe (carotid artery diameter reduction ≥ 70%) as defined by:
• Peak systolic velocity of at least 230 cm/s plus at least one of these:
• End diastolic velocity ≥ 100 cm/s OR
• CTA showing ≥ 70% stenosis OR
• MRA showing ≥ 70% stenosis
• This stenosis has not caused any stroke, transient cerebral ischemia, or other relevant neurological symptoms in the past.
• 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.
• The patient has no known circumstance or condition likely to preclude 1 year follow-up or adherence to the study protocol.
• The patient is independent in their Activities of Daily Living at baseline.
• Patient has the ability to provide informed consent.

You may not qualify if:

• Patient has underlying disease other than atherosclerosis (i.e. autoimmune disease, known active malignancy).
• Patient has documented dementia or screens out based on abnormal Baseline MoCA (≤25) and AD8 (≥2).
• Patient's life expectancy is \< 12 months.
• Patient has advanced renal failure (serum creatinine \> 2.5 mg/dL)
• 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).
• Patient has history of intolerance or allergic reaction to any statins (myotoxicity, hepatic dysfunction, rash, etc.)
• Patient has received an investigational drug within 30 days.
• Patient is pregnant or lactating.
• 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);

Sponsors & Collaborators

• Columbia University: lead

Study Sites (7)

Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

Albany Medical College/The Vascular Group at Albany

Albany, New York, 12208-3479, United States

Location

State University of New York at Buffalo

Buffalo, New York, 14260-7016, United States

Location

New York University School of Medicine

New York, New York, 10016-6402, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cornell University Medical College (Weill)

New York, New York, 10065-4805, United States

Location

MeSH Terms

Conditions

Carotid Stenosis; Stroke

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Sugars

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Carbohydrates

Limitations and Caveats

The study was limited by insufficient enrollment in the statin-naive arm (arm 3/4), resulting in reduced statistical power to detect differences between groups. Recruitment of statin-naïve participants was challenging, likely reflecting widespread baseline statin use in this patient population based on existing evidence supporting their benefit. Due to these recruitment limitations and feasibility constraints, the study was terminated early.

Results Point of Contact

• Title: Edward Connolly, MD
• Organization: Columbia University

esc5@cumc.columbia.edu

212-305-0376

Study Officials

• Edward S Connolly, MD, FACS

  Columbia University Medical Center/New York Presbyterian

  PRINCIPAL INVESTIGATOR

• Eric Heyer, MD, Ph.D.

  Columbia University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurological Surgery; Chair, Department of Neurological Surgery

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: July 29, 2016
• Study Start: June 1, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: May 7, 2026
• Results First Posted: May 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)