BACKGROUND: Experimental evidence has indicated the benefit of simvastatin in 
the treatment of subarachnoid hemorrhage. However, no clinical data are 
available to answer whether a high-dose regimen is more effective than a 
normal-dose regimen, even though the biochemical actions and related 
neuroprotective mechanisms are thought to be dose related.
OBJECTIVE: To determine whether 80 mg simvastatin daily (high dose) over 3 weeks 
initiated within 96 hours of the ictus will reduce the incidence of delayed 
ischemic deficits after subarachnoid hemorrhage compared with 40 mg simvastatin 
daily (normal dose), leading to improvements in clinical outcomes and thus 
cost-effectiveness.
METHODS: The study design is a randomized, controlled, double-blind clinical 
trial (www.ClinicalTrials.gov; identifier: NCT01077206). Two hundred forty 
patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of 
the ictus) from 6 neurosurgical centers are being recruited over 3 years. The 
primary outcome measure is the presence of delayed ischemic deficits. Secondary 
outcome measures include modified Rankin Disability Score at 3 months and 
cost-effectiveness analysis.
EXPECTED OUTCOMES: This will be the first study to clarify whether high-dose 
simvastatin is better than normal-dose simvastatin for patients with acute 
aneurysmal subarachnoid hemorrhage in terms of neurological outcomes and 
cost-effectiveness.
DISCUSSION: In the present trial, we compare high-dose and normal-dose 
simvastatin; we know that another ongoing phase III multicenter trial 
(Simvastatin in Aneurysmal Subarachnoid Haemorrhage; 
http://www.stashtrial.com/home.html) is comparing normal-dose and no 
simvastatin. When the results are interpreted together, the research question of 
a possible beneficial effect of high-dose simvastatin in acute aneurysmal 
subarachnoid hemorrhage could be answered.