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Trial record 1 of 1 for:    NCT02850081
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Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes (STANCE)

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ClinicalTrials.gov Identifier: NCT02850081
Recruitment Status : Recruiting
First Posted : July 29, 2016
Last Update Posted : June 6, 2017
Sponsor:
Information provided by (Responsible Party):
E. Sander Connolly, Columbia University

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.


Condition or disease Intervention/treatment Phase
Carotid Artery Stenosis Strokes Drug: Statin Drug: Atorvastatin Other: Placebo Phase 3

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Observational - Maximal Dose - ARM 1
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.
Experimental: Less Than Maximal Dose - ARM 2
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

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)
Other Name: Pre-existing statin regimen

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

Experimental: Statin Naive - ARM 3
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

A lipid-lowering agent and for prevention of events associated with cardiovascular disease.

10 mg or 80 mg capsules

Other Name: Lipitor




Primary Outcome Measures :
  1. Prevalence of eCD [ Time Frame: 30 Days: 1) Pre-op vs. Post-CEA Day 1 (12-25 hrs post-op) and 2) Pre-op vs. Post-CEA Day 30 ]
    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.


Secondary Outcome Measures :
  1. Prevalence of early mortality [ Time Frame: 1 year ]
    Data will be collected by follow up phone call



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02850081


Contacts
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Contact: Rebeca Aragon Garcia, BS 212-305-4679 ra2356@cumc.columbia.edu
Contact: Josephine U Pucci, BA 2123054679 jup2102@cumc.columbia.edu

Locations
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United States, New Jersey
Valley Hospital Not yet recruiting
Ridgewood, New Jersey, United States, 07450
Contact: Avery Freed    201-389-0194    afreed@valleyhealth.com   
Contact: Kathleen Sayles       KSAYLES@valleyhealth.com   
Principal Investigator: Dorothea Altschul, MD         
United States, New York
Albany Medical College/The Vascular Group at Albany Not yet recruiting
Albany, New York, United States, 12208-3479
Contact: Ryan Kaim       KaimR@mail.amc.edu   
Contact: Angela Sheehan       SheehaA@mail.amc.edu   
Principal Investigator: Courtney Warner, MD         
Sub-Investigator: Ralph C Darling, MD         
State University of New York at Buffalo Not yet recruiting
Buffalo, New York, United States, 14260-7016
Contact: Jennifer Gay    716-440-4231    jgay@ubns.com   
Contact: Reagan O'Toole       rotoole@ubns.com   
Principal Investigator: Adnan Siddiqui, MD         
New York University School of Medicine Not yet recruiting
New York, New York, United States, 10016-6402
Contact: Jacqueline Bott    212-263-2268    jacqueline.bott@nyumc.org   
Principal Investigator: Thomas Maldonado, MD         
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
Contact: Rebecca Apruzzese    212-241-8349    rebecca.apruzzese@mountsinai.org   
Contact: Milerva Santos       milerva.santos@mountsinai.org   
Principal Investigator: J Mocco, MD         
Sub-Investigator: Emilia Bagiella, MD         
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Rebeca Aragon Garcia, BS    212-305-4679    ra2356@cumc.columbia.edu   
Contact: Josephine U Pucci, BA    21123054679    jup2102@cumc.columbia.edu   
Principal Investigator: Edward S Connolly, MD         
Sub-Investigator: Elise A Caccappolo Van Vliet, PhD         
Sub-Investigator: Yaakov Stern, MD         
Sub-Investigator: Richard Buchsbaum         
Sub-Investigator: Eric J Heyer, MD         
Sub-Investigator: Erin L Heinzen-Cox, PhD         
Cornell University Medical College (Weill) Not yet recruiting
New York, New York, United States, 10065-4805
Contact: Ruchita Mehta       rum2006@med.cornell.edu   
Principal Investigator: Peter Connolly, MD         
Sponsors and Collaborators
Columbia University
Investigators
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Principal Investigator: Edward S Connolly, MD, FACS Columbia University Medical Center/New York Presbyterian
Study Director: Eric Heyer, MD, Ph.D. Columbia University

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Responsible Party: E. Sander Connolly, Bennett M. Stein Professor of Neurological Surgery, Dept of Neurological Surgery, Columbia University
ClinicalTrials.gov Identifier: NCT02850081     History of Changes
Other Study ID Numbers: AAAM2407
First Posted: July 29, 2016    Key Record Dates
Last Update Posted: June 6, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No
Keywords provided by E. Sander Connolly, Columbia University:
Carotid endarterectomy
CEA
stroke
asymptomatic stenosis
Additional relevant MeSH terms:
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Carotid Stenosis
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Carotid Artery Diseases
Arterial Occlusive Diseases
Amlodipine
Atorvastatin
Rosuvastatin Calcium
Simvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents