Atorvastatin for treating spontaneous subarachnoid hemorrhage: study protocol for a randomized double-blind placebo-controlled trial

Abstract

Background: Animal studies have confirmed that statins have neuroprotective effects during and following a subarachnoid hemorrhage; however, the therapeutic effect of statins in humans remains controversial. The interpretation of data currently available on the clinical application of statins to spontaneous subarachnoid hemorrhage is limited by the small sample sizes used in the studies, making it difficult to draw valid conclusions regarding the multiple neuroprotective effects of statins. Thus, we propose to perform a randomized double-blind placebo-controlled parallel-group clinical trial to determine the effects of atorvastatin on spontaneous subarachnoid hemorrhage, apoptosis-related factors, and serum inflammatory factors in cerebrospinal fluid and to observe its neuroprotective effect mediated by relieving vasospasm. Methods/Design: This is a randomized parallel-group placebo-controlled double-blind clinical trial. This trial will recruit 300 patients with spontaneous subarachnoid hemorrhage from the Department of Neurosurgery, 101 st Hospital of PLA (Wuxi Taihu Hospital). These patients will be equally and randomly assigned to atorvastatin (40 mg/day) and placebo control groups. Outcomes will be evaluated at baseline, 3, 5, and 14 days after hemorrhage, and 6 months after discharge. The primary outcomes will be the results of computed tomography (CT) angiography combined with CT perfusion imaging and conventional CT. The secondary outcomes will be cerebrospinal fluid analysis, blood testing (tumor necrosis factor α, vascular endothelial growth factor, interleukin-6, and C-reactive protein levels), and the Hunt-Hess classification, the results of transcranial Doppler ultrasonography, and the scores on the Glasgow Coma Scale, the Glasgow Outcome Scale, and the National Institutes of Health Stroke Scale. Discussion: The results of this trial will provide data on the clinical application and neuroregenerative effect of atorvastatin in the acute stage of spontaneous subarachnoid hemorrhage. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005395) on 18 May 2014.