title: High-dose simvastatin for aneurysmal subarachnoid hemorrhage: a multicenter, randomized, controlled, double-blind clinical trial protocol.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China. georgewong@surgery.cuhk.edu.hk
authors: George Kwok Chu
authors: GK
authors: Wong
authors: Min
authors: M
authors: Liang
authors: Haibin
authors: H
authors: Tan
authors: Michael Wing Yan
authors: MW
authors: Lee
authors: Yin Chung
authors: YC
authors: Po
authors: Kwong Yau
authors: KY
authors: Chan
authors: Wai Sang
authors: WS
authors: Poon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D002545:Brain Ischemia / Q000453:epidemiology* / Q000517:prevention & control*; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000453:epidemiology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D019821:Simvastatin