Better 3-month GOS in treatment group (29% versus 9% of treatment group, ). Significantly less delayed cerebral ischemia in treatment group, no difference in angiographic vasospasm
Significantly less cerebral infarction in the nimodipine group (22% compared to 33% in placebo, ). Poor GOS outcomes significantly reduced in nimodipine group at 3-months
Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery
Randomized, double-blind, placebo-controlled of Hunt-Hess I–III SAH patients
Nimodipine IV 0.5 mcg/kg/min × 7–10 days followed by 60 mg q 4 h PO × 21 days total ()
Placebo ()
Primary outcome: delayed ischemic deterioration and CT infarcts Secondary outcomes: GOS at 1–3 years
Significantly fewer deaths caused by delayed cerebral ischemia in nimodipine group () and fewer cerebral infarcts on CT (). No differences in 1–3 year GOS or CT scan
No difference in 3-month GOS. Less symptomatic vasospasm in treatment group (32% versus 46% in placebo group, P < 0.001) and less angiographic vasospasm in treatment group (33% versus 51% of placebo, P < 0.01) and less TCD vasospasm (23% versus 49% of placebo, P < 0.001)
A randomized trial of two doses of nicardipine in aneurysmal subarachnoid hemorrhage. A report of the cooperative aneurysm study
Randomized, double-blind, multicenter study
Nicardipine IV 0.15 mg/kg/h × 14 days (N = 184)
Nicardipine IV 0.075 mg/kg/h × 14 days (N = 181)
Primary outcome: symptomatic vasospasm, adverse drug events Secondary outcomes: 3-month GOS and NIHSS, mortality, disability due to vasospasm, CT infarction
No difference in symptomatic vasospasm or 3-month outcome. More adverse effects in high-dose nicardipine group
Effect of nicardipine prolonged-release implants on cerebral vasospasm and clinical outcome after severe aneurysmal subarachnoid hemorrhage. A prospective, randomized, double-blind phase IIa Study
Randomized, prospective double-blind phase IIa study in clipped SAH patients
Nicardipine prolonged-release implants (10 × 4 mg prolonged release rod shaped polymers) placed in basal cisterns (N = 16)
Control-basal cisterns opened and washed out (N = 16)
Primary outcome: angiographic vasospasm Secondary outcome: delayed ischemic lesion on HCT, 1-year mRS and NIHSS
Angiographic vasospasm significantly reduced in treatment group (7% versus 73% in controls, P < 0.05). No significant difference in CT infarct. Decreased mortality in treatment group (6% versus 38% in control group, P = 0.042) and better 1-year mRS and NIHSS (P = 0.0001)
Comparative clinical trial of epsilon amino-caproic acid and tranexamic acid in the prevention of early recurrence of subarachnoid hemorrhage
Randomized trial
Epsilon amino-caproic acid 6 g q 6 h IV continued until surgery or discharge (N = 90)
Tranexamic acid 1 g q 6 h IV continued until surgery or discharge (N = 61)
Primary outcome: recurrent hemorrhage diagnosed clinically by HCT, LP, or autopsy Secondary outcome: delayed ischemic deficit diagnosed by clinical deterioration, angiographic vasospasm, and infarct on HCT
Rebleeding occurred in 8% of aminocaproic-acid-treated patients and 10% of tranexamic acid treated patients. Delayed ischemic deficits occurred in 7% of aminocaproic acid patients and 5% of tranexamic acid patients. Mortality was 11% in each group. P = NS for all outcomes
Rebleeding reduced from 24% in control group to 9% in treatment group (P < 0.001), but with concurrent increase in ischemic complications (24% in treatment group versus 15% in placebo, P < 0.01). No difference in 3 month GOS
No difference in 3-month GOS. Significant decrease in rebleeding from 33% in placebo group to 19% in treatment group. No difference in delayed cerebral ischemia, hydrocephalus, or postoperative ischemia
Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study
Randomized, placebo-controlled trial
Tranexamic acid 1 g IV bolus, then 1 g IV q 6 hours until aneurysm repair or 72 hours post ictus. (N = 254)
Treatment group had reduced rebleeding rate of 2.4% compared to 10.8% in the placebo group (P < 0.01). More favorable outcome in the treatment group (74.8% compared to 70.5% in the control group, P = NS). No increased risk of ischemia
A double-blind clinical evaluation of the effect of nizofenone on delayed ischemic neurological deficits following aneurysmal rupture
Randomized, placebo controlled trail
Nizofenone for 5–10 days (N = 42)
Placebo (N = 48)
Primary outcome: delayed ischemic neurological deficits with angiographically confirmed vasospasm. Secondary outcomes: one-month disability index, motor, and speech function
No difference in delayed ischemic events between treatment groups. Among patients with vasospasm, those who received nizofenone had better one-month functional outcomes (P < 0.05)
Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage
Randomized, controlled, single-center study
Edaravone 30 mg IV BID × 14 days (N = 49)
Control (usual treatment) (N = 42)
Primary outcome: delayed ischemic neurological deficits Secondary outcomes: cerebral infarction due to vasospasm, 3-month GOS
No difference in delayed ischemic neurological deficits between treatment and control groups. Less cerebral infarction in treatment group (0% versus 66%, P = 0.028). Poor outcome caused by vasospasm 0% in treatment group and 71% in control group (P = 0.046)
Eicosapentaenoic Acid Cerebral Vasospasm Therapy Study (EVAS)
Randomized, controlled, open label, multicenter, efficacy study of surgically clipped SAH patients
Eicosapentaenoic acid (omega 3 fatty acid) 900 mg TID × 30 days (N = 81)
Control (usual treatment) (N = 81)
Primary outcome: symptomatic vasospasm or infarct on HCT Secondary outcome: 1-month GOS
Symptomatic vasospasm occurred significantly less in the treatment group (15% versus 30% in controls, P = 0.022) as did infarction from vasospasm (7% versus 21% in controls, P = 0.012)
Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomized, double-blind, placebo-controlled trial
Randomized, double-blind, placebo-controlled study of ruptured (WFNS 1–3) and unruptured aneurysms undergoing endovascular repair
NA-1 2.6 mg/kg infusion over 10 minutes (N = 92)
Placebo (N = 93)
Primary outcome: safety, number and volume of ischemic strokes on MRI DWI and FLAIR 12–96 hours after infusion Secondary outcome: 30-day mRS, NIHSS, neurocognitive outcome
No difference in MRI lesion volume, but fewer ischemic lesions in NA-1 group compared to placebo (P = 0.012). In the SAH subgroup (20% of cohort) their MRI number and ischemic volume was significantly less in the treatment group. No difference in 30 day NIHSS or mRS between groups
Simvastatin reduces vasospasm After aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial
Randomized, placebo-controlled pilot trial
Simvastatin 80 mg qd for 14 days (N = 19)
Placebo (N = 20)
Primary outcome: delayed ischemic neurological deficit confirmed by TCD or angiography. Secondary outcomes: liver transaminases, CK, von Willebrand factor, S100
Vasospasm occurred in 26% of treatment group compared to 60% of placebo group (P < 0.05). No differences in transaminitis or myositis. VWF and S100 were significantly lower in the treatment group (P < 0.05)
Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed Ischemic deficits after aneurysmal subarachnoid hemorrhage. A phase II randomized placebo-controlled trial
Randomized placebo-controlled, phase II Trial
Pravastatin 40 mg PO qd × 14 d (N = 40)
Placebo (N = 40)
Primary outcome: incidence, severity, and duration of vasospasm on TCD, duration of impaired autoregulation measured by transient hyperemic response on TCD Secondary outcome: vasospasm-related delayed ischemic deficits, disability at discharge
TCD vasospasm and severe vasospasm were reduced in the treatment group (P = 0.006 and P = 0.044, resp.). Duration of impaired autoregulation shortened in treatment group (P < 0.01). Vasospasm-related delayed ischemic deficits was reduced (P < 0.001) and mortality was reduced (P = 0.037)
A randomized, double-blind, placebo-controlled pilot study of simvastatin in aneurysmal subarachnoid hemorrhage
Randomized, double-blind, placebo-controlled pilot study
Simvastatin 80 mg qd in statin naïve Fisher 3 SAH until discharge or 21 days (N = 19)
Placebo (N = 20)
Primary outcome: death and drug morbidity (elevated CK, transaminases) Secondary outcomes: TCD, angiographic or clinical vasospasm, vasospasm-related infarcts, clinical outcomes at discharge, cardiac, and infectious morbidities
Mortality in 0% treatment group and 15% placebo group. Angiographically confirmed vasospasm in 26% treatment group and 25% placebo group. Vasospasm infarcts in 11% treatment group and 25% placebo group. All differences P = NS
Biological effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled randomized trial
Double-blind, placebo-controlled randomized trial
Simvastatin 80 mg PO × 15 days (N = 16)
Placebo (N = 16)
Primary outcome: effect of simvastatin on laboratory parameters of endothelial function, fibrinolysis, coagulation, inflammation and cholesterol Secondary outcomes: TCD vasospasm, clinical signs of DCI, 3- and 6-month GOS
Simvastatin group had significantly lower total cholesterol and LDL, but no differences in coagulation, fibrinolysis, endothelium function, or inflammation. No differences in TCD vasospasm, clinical DCI, or poor outcome
Vergouwen et al., J Cereb Blood Flow Metab 2009 [27]
Aneurysm repair
Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study
Randomized, prospective study of Hunt Hess grade I–III SAH patients
Acute surgery (day 0–3 after SAH) (N = 71)
Intermediate surgery (day 4–7 after SAH) (N = 70) Late surgery (day 8 or later after SAH) (N = 70)
Primary outcome: 3-month dead, dependent or independent. Secondary outcomes: Neurological deficit from direct effect of initial bleed, complication of surgery, confirmed rebleeding, delayed ischemic deterioration, hydrocephalus, extracranial complications
Acute surgery patients were more often independent at 3-months (92% versus 79% in intermediate timing and 80% in the late timing group, P < 0.01). Mortality was 6% in the early surgery group versus 13% in the late surgery group (P = NS)
International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial
Randomized, unblinded trial of SAH patients with an aneurysm judged technically suitable for either clipping or coiling and clinical equipoise
Surgical clipping (N = 1070)
Endovascular treatment by detachable platinum coils (N = 1073)
Primary outcome: 1-year mRS 3–6 versus 1-2 Secondary outcomes: rebleeding, quality of life at 1 year (euroQol), frequency of epilepsy, cost effectiveness, neuropsychological outcomes
Dependent or dead at 1 year: 23.7% endovascular versus 30.6% clipping (P = 0.0019).
Molyneux et al., ISAT Collaborative Group, Lancet 2002 [29]
International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion
Randomized, unblinded trial of SAH patients with an aneurysm judged technically suitable for either clipping or coiling and clinical equipoise
Surgical clipping (N = 1070)
Endovascular treatment by detachable platinum coils (N = 1073)
Primary outcome: 1-year mRS 3–6 versus 1-2 Secondary outcomes: rebleeding, quality of life at 1-year (Euroqol), frequency of epilepsy, cost effectiveness, neuropsychological outcomes
Dead or dependent at 1-year: 23.5% of endovascular group versus 30.9% of clipping group. ARR 7.4%. Early survival advantage of coiling maintained up to 7 years (P = 0.03). Lower risk of epilepsy in coiled group but higher late rebleeding risk in coiled group
Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand
Double-blind, randomized, vehicle-controlled study in men and women with aneurysmal SAH
Tirilazad 0.6 mg/kg/ (N = 257) Tirilazad 2 mg/kg/d (N = 249) Tirilazad 6 mg/kg/d (N = 256) up to 11 days
Placebo containing citrate vehicle (N = 253)
Primary outcome: Symptomatic vasospasm Secondary outcome: 3-month GOS, NIHSS, infarct volume on head CT
The subgroup 6 mg/kg treatment arm had reduced mortality (P = NS) and better 3-month GOS (P = NS) compared to placebo. Less symptomatic vasospasm in 6 mg/kg group, but not significant. Men showed more benefit than women. No significant improvement with lower dosing groups
A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America
Double-blind, randomized, vehicle-controlled study in men and women with aneursymal SAH
Tirilazad 2 mg/kg/d (N = 298) Tirilazad 6 mg/kg/d (N = 299) up to 11 days
Placebo containing citrate vehicle (N = 300)
Primary outcome: mortality at 76 days Secondary outcome: 3-month GOS and NIHSS, infarct volume on head CT symptomatic vasospasm, incidence, and severity of angiographic vasospasm
No difference in mortality, favorable GOS outcome, or employment between groups. No differences in symptomatic or angiographic vasospasm
Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I a cooperative study in Europe, Australia, New Zealand, and South Africa
Double-blind, randomized, vehicle-controlled study in women with aneurysmal SAH
Tirilazad mesylate 15 mg/kg/d IV hours for 11 days (N = 405)
Placebo containing citrate vehicle (N = 414)
Primary outcome: 91-day mortality Secondary outcome: 3-month GOS, clinical vasospasm, use of hypervolemic hypertensive therapy, neurological worsening from vasospasm, cerebral infarction, use of angioplasty, safety endpoints
Mortality rates and 3-month GOS not different between groups. Lower symptomatic vasospasm in tirilazad group (24.8% versus 33.7% in placebo group, P = 0.005). Cerebral infarction 8% in treatment group versus 13% in placebo group (P < 0.04)
Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneursymal subarachnoid hemorrhage. Part II a cooperative study in North America
Double-blind, randomized, vehicle-controlled study in women with aneurysmal SAH
Tirilazad mesylate 15 mg/kg/d IV up to 11 days (N = 410)
Placebo containing citrate vehicle (N = 413)
Primary outcome: mortality at 91 days in WFNS grade IV-V patients Secondary outcomes: 3 month GOS or clinical vasospasm 1–14 days from dosing, use of hypervolemic hypertensive therapy, neurological worsening from vasospasm, cerebral infarction, use of angioplasty, safety endpoints
No differences in mortality when analyzing the entire population. No difference in GOS, symptomatic vasospasm, vasospasm severity. In WFNS grades IV-V, lower mortality in treatment group (24.6% versus 43.4% in placebo, P = 0.016). In WFNS I–III improved GOS in placebo group (83.3% versus 76.7% in treatment group, P = 0.04)
A randomized trial of intraoperative, intracisternal tissue plasminogen activator for the prevention of vasospasm
Randomized, double-blinded, placebo-controlled, multicenter study
rTPA 10 mg intracisternal at the time of aneurysm clipping (N = 51)
Placebo vehicle (N = 49)
Primary outcome: angiographic vasospasm Secondary outcome: mortality, 3-month GOS, symptomatic vasospasm, clot clearance on CT, TCD velocities, use of HHH on angioplasty to treat vasospasm
No difference in angiographic vasospasm, vasospasm treatment, TCD velocities, mortality, or 3-month GOS
Efficacy of low-dose tissue-plasminogen activator intracisternal administration for the prevention of cerebral vasospasm after subarachnoid hemorrhage
Randomized, controlled trial
Intermittent Tisokinase 960,000 IU via cisternal drain (N = 20) Continuous infusion Tisokinase 1920 IU/h × 48 h via cisternal drain (N = 20)
Control (standard treatment) (N = 20)
Primary outcome: clearance of subarachnoid clots by HCT Secondary outcome: delayed cerebral ischemia, 3-month mRS and GOS
Subarachnoid clot by HCT and delayed cerebral ischemia were significantly less in the treatment groups compared to control (P < 0.05). The intermittently treated group had better neurological outcomes than the control group (P < 0.05)
Randomized controlled trial of acetylsalicylic Acid in aneurysmal subarachnoid hemorrhage: the MASH study
Randomized controlled pilot study; factorial design (magnesium versus placebo and ASA versus placebo, separated a priori)
Aspirin 100 mg PR qd × 14 days within 12 hours of aneurysm occlusion. (N = 87)
Placebo (N = 74)
Primary outcome: delayed ischemic neurological deficits within 3-months of SAH consisting of HCT infarcts plus clinical decline Secondary outcome: new CT infarcts of any cause, postop hemorrhage, mRS ≥ 4, mRS ≥ 1
No difference in delayed ischemic events, CT infarction, or 3-month outcomes
Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage
Randomized, placebo controlled, multicenter trial
Fludrocortisone 400 mcg/day BID × 12 days PO or IV (N = 46)
Placebo (N = 45)
Primary outcome: plasma volume change, fluid balance, sodium balance Secondary outcome: delayed cerebral ischemia within 28 days and 28-day GOS
Treatment reduced negative sodium balance (P = 0.014) but did not affect plasma volume. No significant difference in cerebral ischemia (22% versus 31% in controls, P = 0.349). Similar outcome in each group
Randomized, double-blind, placebo-controlled, pilot trial of high-dose methylprednisolone in aneurysmal subarachnoid hemorrrhage
Randomized, double-blind, placebo-controlled, single center study
Methylprednisolone 16 mg/kg IV qd × 3 days (N = 49)
Placebo (N = 46)
Primary outcome: symptomatic vasospasm and infarct on HCT Secondary Outcomes: 1 year GOS, functional outcome scale, and severity of delayed ischemic deficits
No significant difference in symptomatic vasospasm or infarct on HCT. No difference in 1-year GOS or delayed ischemic deficits at 3-months. Poor outcome by functional outcome scale was reduced in treatment group (P = 0.02)
Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a phase II randomized, double-blind, placebo-controlled trial
Phase II randomized, double-blind, placebo-controlled trial
Erythropoietin IV (30,000 u) every 48 h for a total of 90,000 U (N = 40)
Placebo (N = 40)
Primary outcome: incidence, duration and severity of TCD vasospasm; duration of impaired autoregulation by TCD Secondary outcome: incidence of delayed ischemic deficits, mRS, GOS, and NIHSS at discharge and 6-months
No differences in incidence of TCD vasospasm or adverse events. Treatment group had less severe TCD vasospasm (P = −0.037), reduced delayed ischemic deficits/delayed cerebral infarcts (P = 0.001), and shortened duration of impaired autoregulation (P < 0.001) and more favorable discharge outcome (P = 0.039)
Primary outcomes: days of core temp > 100.4 F, ventilator-free days, hemoglobin level Secondary outcomes: NIHSS, mRS, and MRI at 14 days, mRS at 28 days and 3-months
Higher target Hgb resulted in more transfusions. No difference in safety endpoints. Number of MRI infarcts, NIHSS, and mRS similar between both groups at all timepoints
The Albumin in Subarachnoid Hemorrhage multicenter pilot clinical trial: safety and neurologic outcomes (ALISAH)
Open label, dose escalation study
Albumin in 3 tier doses: 0.625 g/kg/d (N = 20), 1.25 g/kg/d (N = 20), 1.875 g/kg/d (N = 7) × 7 days (N = 47 total)
NA
Primary outcomes: severe to life threatening heart failure, anaphylaxis Secondary outcomes: functional outcome at 3-months
Doses up to 1.25 g/kg/d × 7 days tolerated without dose-limiting complications. Trend toward better outcomes in 1.25 g/kg/d dose compared to 0.625 g/kg/d
Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling (CONSCIOUS 3)
Phase 3 randomized placebo-controlled double-blinded; terminated early for futility (planned N = 1500)
Clazosentan (5 or 15 mg/h IV up to 14 days) (N = 194)
Placebo (N = 189)
Primary outcomes: cerebral vasospasm related morbidity (DCI/DIND/vasospasm therapy), all-cause mortality at 6 weeks Secondary outcomes: 12-week GOSE
Clazosentan 15 mg/h significantly reduced vasospasm-related morbidity/all-cause mortality at 6 weeks but did not improve long-term outcome Primary outcome: 24% in clazosentan 5 mg/h and 27% in placebo group P = NS and 15% in clazosentan 15 mg/h P = 0.007 Poor outcome in 25% of clazosentan 5 mg/h, 28% clazosentan 15 mg/h, and 24% of placebo group P = NS.
Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage: A randomized controlled trial
Randomized, controlled, single-center study
High-volume management (with colloid and crystalloid) to target PADP ≥ 14 mmHg or CVP ≥ 8 mmHg (N = 41)
Normal volume management (with colloid and crystalloid) to target PADP ≥ 7 mmHg or CVP ≥ 5 mmHg (N = 41)
Primary outcome: CBF by Xenon CT and blood volume by tagged RBC Secondary outcomes: symptomatic vasospasm, medical complications, GOS and 3, 6, and 12 months
High-volume management patients received significantly more fluid but there was no effect on net fluid balance or blood volume. No difference in CBF or vasospasm
Intravenous magnesium sulfate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized double-blinded, placebo-controlled, multicenter phase III trial
Randomized double-blinded, placebo-controlled, multicenter phase III trial.
MgSO4 IV infusion to 2x baseline value (20 mmol over 30 minutes then continuous infusion of 80 mmol/d × 14 days; maximum allowed serum Mg of 2.5 mmol/L (N = 169)
Equivalent volume of normal saline infusion. Occasional changes in infusion rates to maintain blinding. (N = 158)
Primary outcome: 6-month GOSE 5–8 Secondary outcome: clinical vasospasm during initial 2 weeks, 6-month mRS, Barthel Index, and Short Form 36
Favorable 6-month GOSE (5–8) 64% of Mg group and 63% placebo (P = NS) No difference in mRS, Barthel, Short Form 36, or clinical vasospasm. No subgroup differences
Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized clinical trial
Unblinded, randomized phase II trial of Fisher III and Fisher III + IV SAH patients after clipping or coiling within 96 h of rupture
Balloon angioplasty of bilateral A1, M1, P1, basilar, intradural vertebral artery, and supraclinoid ICA. Protocol later revised to exclude A1 and P1 (N = 85)
No prophylactic balloon angioplasty (N = 85)
Primary outcome: 3-month GOS Secondary outcome: delayed ischemic neurological deficit, TCD vasospasm, ICU, and hospital length of stay
Nonsignificant difference in delayed ischemic neurological deficits but less therapeutic angioplasty required in treatment group (P = 0.03). No significant difference in GOS outcomes. LOS similar. Four patients had procedure related vessel perforation, three of whom died
Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial
Randomized, placebo controlled, double-blind, multicenter study in Hunt Hess I–IV clipped SAH patients
Fasudil (AT877) 30 mg IV over 30 minutes, TID × 14 days (N = 131)
Placebo (N = 136)
Primary outcome: reduction of incidence or severity of angiographic vasospasm, reduction of incidence and size of low-density CT lesions due to vasospasm, reduction of incidence of symptomatic vasospasm, poor outcome (1-month GOS) due to vasospasm
Fasudil significantly reduced angiographic vasospasm (38% in treatment group versus 61% in placebo group, P = 0.0023), infarcts reduced (16% in treatment versus 38% in placebo group, P = 0.0013) and symptomatic vasospasm reduced (35% in treatment versus 50% in placebo, P = 0.0247). Poor outcome (GOS 1–4) attributable to vasospasm occurred in 12% of treatment group and 26% of placebo group (P = 0.0152). No serious adverse events in fasudil group
Efficacy and safety of fasudil in patients with subarachnoid hemorrhage: final results of a randomized trial of fasudil versus nimodipine
Randomized, open label, multicenter study of SAH Hunt-Hess grade I–IV clipped patients
Fasudil 30 mg IV TID × 14 days (N = 63)
Nimodipine 1-2 mg/h × 14 days (N = 66)
Primary outcome: symptomatic vasospasm or infarct on HCT Secondary outcome: 1-month GOS
No difference in symptomatic vasospasm or HCT infarcts. Improved GOS outcomes in fasudil group (good outcome in 74.5% versus 61.7% in nimodipine group, P = 0.040)
The effect of intensive insulin therapy on infection rate, vasospasm, neurologic outcome and mortality in neurointensive care unit after intracranial aneurysm clipping in patients with acute subarachnoid hemorrhage: a randomized prospective Pilot trial
Primary outcome: GOS at 90 days Secondary outcomes: 90-day mRS, Barthel Index, NIHSS, neuropsych testing, adverse events
No difference in 90 day GOS. Good GOS in 66% of hypothermia versus 63% of control patients (P = NS). No differences in death, length of stay, or discharge disposition. Postoperative bacteremia more common in the hypothermia group (5% versus 3%, P = 0.05)
