Simvastatin For Intracerebral Hemorrhage Study

• Mortality [ Time Frame: 30 days ] [ Designated as safety issue: No ]
• Functional outcomes using Modified Rankin Score, Barthel Index [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Study Objective: To analyze if statins are effective in ameliorating perihematomal edema evolution thereby reducing mortality and improving functional outcomes following spontaneous intracerebral hemorrhage (ICH).

Intracerebral hemorrhage (ICH) causes 10% to 15% of first-ever strokes, with a 30-day mortality rate of 35% to 52% with only 20% expected to be functionally independent at 6 months. No medical or surgical interventions have been found to alter the natural evolution of this disease. The high risk for mortality and poor outcomes seems to occur despite relatively small hematoma volumes and small amounts of neuronal tissue at risk for injury. The reasons for this observation remain unknown; however perihematomal edema formation and inflammation that follows ICH seems to play an important role.

The Simvastatin for Intracerebral Hemorrhage Study is a prospective double blinded placebo controlled randomized (1:1) clinical trial that compares outcomes in patients receiving generic simvastatin 80 mg for 14 days or until death or discharge with patients in the placebo group.

The hypothesis for our study is that statins ameliorate perihematomal edema evolution thereby reducing mortality and improving functional outcomes following Intracerebral Hemorrhage (ICH). This hypothesis in turn is based on animal data showing suppression of inflammatory reaction and improved neurological outcomes following administration of statins to rodents with experimental ICH, and on a retrospective review of patients admitted to The Johns Hopkins Hospital over the last 7 years with spontaneous ICH which showed significantly better outcomes (decreased 30 day mortality secondary to decreased perihematomal edema) in patients on statins at the time of admission.

• Drug: Simvastatin 80 mg
  Patients in study arm 1 will receive simvastatin 80 mg once daily for 14 days or until death or discharge.
• Drug: Placebo
  Patients in study arm II will receive placebo once daily for 14 days or until death or discharge.

• Experimental: I
  Simvastatin Group
  Intervention: Drug: Simvastatin 80 mg
• Placebo Comparator: II
  Placebo Group
  Intervention: Drug: Placebo

• Naval NS, Abdelhak TA, Zeballos P, Urrunaga N, Mirski MA, Carhuapoma JR. Prior statin use reduces mortality in intracerebral hemorrhage. Neurocrit Care. 2008;8(1):6-12.
• Naval NS, Abdelhak TA, Urrunaga N, Zeballos P, Mirski MA, Carhuapoma JR. An association of prior statin use with decreased perihematomal edema. Neurocrit Care. 2008;8(1):13-8.

Inclusion Criteria:

• Patient with CT evidence of ICH admitted within 24 hours of onset of symptoms.

Exclusion Criteria:

• Age < 18 or > 85
• Admission GCS < 6
• ICH volume < 10 cc
• ICH secondary to trauma, aneurysm, AVM, tumor or post surgical
• Multiple ICH
• Associated Subdural hematoma or significant Subarachnoid hemorrhage
• History of prior neurologic disease with mRS > 1
• Hematoma evacuation, hemicraniectomy, clot lysis
• Myopathy
• Active Liver disease
• Pregnancy
• Statin allergy
• Patients on statins prior to admission
• Patients with an acute indication for statin therapy (Unstable angina)

• National Center for Research Resources (NCRR)
• National Institutes of Health (NIH)