Neuroprotection With Statin Therapy for Acute Recovery Trial Phase 2 "NeuSTART2"

Completed

Phase 2 Results N/A

Trial Description

This trial will be a phase 2 randomized safety study in which ischemic stroke patients will be randomly assigned within 24 hours of symptom onset to placebo or standard dose lovastatin versus short-term high-dose lovastatin 640 mg per day for 3 days. The primary outcome of this Phase 2 study will be musculoskeletal and hepatic toxicity, defined by clinical and laboratory criteria, with a 3-month follow-up period (± 1 week). Secondary outcomes will include neurological outcome (National Institute of Health (NIH) Stroke Scale), functional outcomes (Barthel Index), and handicap (modified Rankin scores). Effects on inflammatory markers and lipid levels will also be assessed.

Detailed Description

This is a phase 2 randomized, blinded and controlled safety study in patients with ischemic stroke. The time window for enrollment will be within 0-24 hours of symptom onset. For patients who are found with the stroke on awakening, it will be assumed that the stroke occurred the last time that the patient was known to be normal. All patients will be identified by the stroke acute care team in the emergency room of the participating centers, or in some cases, on the floor services of the hospital (i.e., for patients with stroke occurring in hospital). If preliminary data indicate that the patient meets eligibility criteria the patient (or legally authorized representative) will be approached about participation in the study, and consent obtained. Surrogate consent will be allowed at centers at which this is permitted according to regulations. Patients who are consented through a surrogate and subsequently regain capacity, will be approached and reconsented to continue in the study.
The intervention chosen for this trial is either (1) placebo for patients not taking a statin at the time of admission OR lovastatin 80 mg in place of their regular statin for patients taking a statin (atorvastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin, lovastatin) at time of enrolment VERSUS (2) oral lovastatin at dosage of 640 mg daily for 3 days. The time of first dose will be considered time 0. Patients will be administered the total daily dose in four daily divided doses (i.e., QID schedule). After the initial 3 days of acute dosage, all patients will receive statin therapy at the discretion of their treating physician.

Conditions

Interventions

  • Lovastatin (Mevacor)Drug
    Other Names: Mevacor
    Intervention Desc: For patients already on statins, either standard dose lovastatin 80 mg daily for three days versus short-term, high-dose lovastatin 640 mg per day for 3 days.
    ARM 1: Kind: Experimental
    Label: High Dose Lovastatin vs Low Dose Lovastatin
    Description: Previous Statin Use
    ARM 2: Kind: Experimental
    Label: High Dose Lovastatin vs Placebo
    Description: Statin Naive
    ARM 3: Kind: Experimental
    Label: High Dose vs Low Dose Lovastatin
    Description: Previous Statin Use
  • Placebo Drug
    Intervention Desc: Placebo for 3 days
    ARM 1: Kind: Experimental
    Label: High Dose Lovastatin vs Placebo
    Description: Statin Naive
    ARM 2: Kind: Experimental
    Label: Placebo
    Description: Placebo will be administered orally to patients who were NOT taking statin therapy at the time of enrolment
  • Low Dose Lovastatin Drug
    Other Names: Mevacor
    Intervention Desc: 80 mg daily for 3 days
    ARM 1: Kind: Experimental
    Label: Low Dose Lovastatin
    Description: Lovastatin 80 mg daily for three days will be administered orally to patients who were taking statin therapy at the time of enrolment
  • High Dose Lovastatin Drug
    Other Names: Mevacor
    Intervention Desc: 640 mg daily for 3 days
    ARM 1: Kind: Experimental
    Label: High Dose Lovastatin
    Description: High dose lovastatin (640 mg daily for three days) will be administered orally

Trial Design

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

Outcomes

Type Measure Time Frame Safety Issue
Primary Increase in Liver Function Tests (LFTs) 90 Days Yes
Primary Increase in Creatine Kinase (CK) 90 days Yes
Secondary Score on NIH Stroke Scale 90 days No
Secondary Barthel Index Score 90 days No
Secondary Modified Rankin scores 90 days No

Sponsors