Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes "STANCE"

Recruiting

Phase 3 Results N/A

Trial Description

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.

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.

Conditions

Interventions

  • Atorvastatin (LipitorĀ®)Drug
    Other Names: Lipitor
    Intervention Desc: A lipid-lowering agent and for prevention of events associated with cardiovascular disease. 10 mg or 80 mg capsules
    ARM 1: Kind: Experimental
    Label: Statin Naive
    Description: Patients on no pre-existing statin regimen will be randomized to atorvastatin 10 mg or atorvastatin 80 mg for 2 weeks before their CEA
    ARM 2: Kind: Experimental
    Label: Statin Naive - ARM 3
    Description: Patients on no pre-existing statin regimen will be randomized to Atorvastatin 10 mg or Atorvastatin 80 mg for ~2 weeks before their CEA
  • Statin Drug
    Other Names: Pre-existing statin regimen
    Intervention Desc: 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)
    ARM 1: Kind: Experimental
    Label: Less Than Maximal Dose
    Description: Patients on a pre-existing statin regimen at a lower dose (less than maximal) will be randomized to maintain their current dose plus placebo or increase their dose 2 weeks before their CEA
    ARM 2: Kind: Experimental
    Label: Less Than Maximal Dose - ARM 2
    Description: 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.
  • Placebo Drug
    Intervention Desc: A placebo pill will be used for patients that are to maintain their current dose of statins prior to their CEA.
    ARM 1: Kind: Experimental
    Label: Less Than Maximal Dose
    Description: Patients on a pre-existing statin regimen at a lower dose (less than maximal) will be randomized to maintain their current dose plus placebo or increase to maximal dose for 2 weeks before their CEA
    ARM 2: Kind: Experimental
    Label: Less Than Maximal Dose - ARM 2
    Description: 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.

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator)
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Prevalence of eCD 30 days postoperative No
Secondary Prevalence of early mortality 3 months postoperative No

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