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.
ABBREVIATIONS: DID, delayed ischemic deficit
CBF, cerebral blood flow
SAH, subarachnoid hemorrhage
*Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China;
‡Department of Neurosurgery, Eighth Affiliated Hospital of Guangxi Medical University, Guangxi, China;
§Department of Neurosurgery, Sichuan Province People’s Hospital, Sichuan, China;
¶Department of Neurosurgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China;
‖Department of Neurosurgery, Princess Margaret Hospital, Hong Kong, China;
#Department of Neurosurgery, Kwong Wah Hospital, Hong Kong, China
Correspondence: George Kwok Chu Wong, Department of Surgery, 4/F Clinical Science Bldg, Prince of Wales Hospital, 30-32 Ngan Shing St, Shatin, New Territories, Hong Kong SAR, China. E-mail: email@example.com
Received January 11, 2013
Accepted January 15, 2013