Clinical Trial: Neuroprotection With Statin Therapy for Acute Recovery Trial Phase 2

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2 Safety Study in Which Ischemic Stroke Patients Will be Randomized Within 24 Hours of Symptom Onset to Placebo or Oral Lovastatin 640 mg Per Day for 3 Days.

Brief Summary: 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 Summary:

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.


Sponsor: Mitchell S Elkind

Current Primary Outcome: Increase in Liver Function Tests (LFTs) [ Time Frame: 90 Days ]

Primary safety outcome: the development of clinical or laboratory evidence of major hepatic toxicity within 7 days of treatment onset or the development of clinical or laboratory evidence of rhabdomyolysis within 7 days of treatment onset.

The primary safety outcome will be defined as:

Liver toxicity: LFT increase at any time point > 3X upper limit of normal or development of jaundice, otherwise unexplained coagulopathy, or other clinical evidence of hepatitis or liver failure;

or

Muscle toxicity: An increase in CK (Creatine Kinase) at any time point > 10 X upper limit of normal, or clinical evidence of muscle pain or weakness not related to the stroke and associated with CK > 5 X upper limit of normal.



Original Primary Outcome:

  • Increase in Liver Function Tests (LFTs) [ Time Frame: 90 Days ]

    Primary safety outcome: the development of clinical or laboratory evidence of major hepatic toxicity within 7 days of treatment onset.

    The primary safety outcome will be defined as:

    Liver toxicity: LFT increase at any time point > 3X upper limit of normal or development of jaundice, otherwise unexplained coagulopathy, or other clinical evidence of hepatitis or liver failure.

  • Increase in Creatine Kinase (CK) [ Time Frame: 90 days ]

    Secondary safety outcome: the development of clinical or laboratory evidence of rhabdomyolysis within 7 days of treatment onset.

    The secondary safety outcome will be defined as:

    An increase in CK at any time point > 10 X upper limit of normal, or clinical evidence of muscle pain or weakness not related to the stroke and associated with CK > 5 X upper limit of normal.



Current Secondary Outcome:

  • Score on NIH Stroke Scale [ Time Frame: 90 days ]
    Measure of neurological outcomes.
  • Barthel Index Score [ Time Frame: 90 days ]
    Measure of functional outcomes.
  • Modified Rankin scores [ Time Frame: 90 days ]
    Measure of handicap.


Original Secondary Outcome: Same as current

Information By: Columbia University

Dates:
Date Received: October 30, 2013
Date Started: February 2009
Date Completion: March 2017
Last Updated: May 5, 2016
Last Verified: May 2016