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| Trial name | Study design | Treatment group | Control group | Target enrollment | Outcome measure | PI | Comments |
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| Statins |
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| Statins and cerebral blood flow in SAH | Randomized, double-blind efficacy study | Simvastatin 80 mg/d for 21 days | Placebo | 60 | Primary outcome: resting CBF and autoregulation 7–10 days after SAH
Secondary outcomes: OEF and CMRO2 7–10 days after SAH | Michael Diringer,
NCT00795288 | Uses PET to understand the mechanism of statin use in vasospasm |
| The role of statins in preventing cerebral vasospasm secondary to subarachnoid hemorrhage | Randomized, double-blind, parallel assignment | Simvastatin 80 mg PO qd × 21 days | Placebo | 80 | Primary outcome: 6-month clinical outcome | Eberval Figueiredo,
NCT01346748 | — |
| Use of simvastatin for the prevention of vasospasm in aneurysmal subarachnoid hemorrhage | Randomized, double-blind, parallel assignment efficacy trial | Tier 1: Simvastatin 40 mg × 21 d or
Tier 2:
Simvastatin 80 mg × 21 d | Placebo | 150 | Primary outcome:
21-day GOS, mRS, and Barthel Index
Secondary outcome: clinical vasospasm | Ben Roitberg,
NCT00487461 | — |
| High-dose simvastatin for aneurysmal subarachnoid hemorrhage (HDS-SAH) | Randomized, parallel assignment, double-blind efficacy study | Simvastatin 80 mg PO × 21 days | Simvastatin 40 mg PO × 21 days | 240 | Primary outcome:
delayed ischemic neurological deficit
Secondary Outcomes:
LFTs, rhabdomyolysis, 3-month mRS, cost effectiveness | George Wong, NCT01077206 | There may be a biochemical and neuroprotective dose-related relationship between simvastatin and delayed ischemic neurological deficits. |
Simvastatin in aneurysmal subarachnoid hemorrhage (STASH):
a multicentre randomised controlled clinical trial | Randomized, placebo-controlled, double-blind phase III trial | Simvastatin 40 mg PO qd × 21 days | Placebo | 1600 | Primary outcome: 6-month mRS
Secondary outcome: need and intensity of delayed ischemic deficit rescue therapy, incidence and duration of delayed ischemic deficits, incidence and severity of sepsis, length of stay, discharge disposition | Peter Kirkpatrick,
NCT00731627 | Simvastatin may improve CBF and inflammation following SAH |
|
| Aneurysm repair |
|
| International subarachnoid aneurysm trial II comparing clinical outcomes of Surgical clipping and endovascular coiling for ruptured intracranial aneurysms not included in the original ISAT study (ISAT II) | Randomized, open label, safety/efficacy study of WFNS I–IV | Surgical Clipping | Endovascular Coiling | 1724 | Primary outcome: 12-month mRS > 2
Secondary outcomes: ICH following treatment, failure of aneurysm occlusion, all cause morbidity and mortality, aneurysm recurrence, hospitalization > 20 days or discharge other than home, aneurysm rebleed | Tim Darsaut, Max Findlay, and Jean Raymond,
NCT01668563 | ISAT included primarily small anterior circulation aneurysms. The optimal treatment of other locations and sizes of aneurysms remains unclear and coiling may not be as durable as clipping |
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| Lipid peroxidation inhibitor |
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| Acetaminophen in aSAH to inhibit lipid peroxidation and cerebral vasospasm | Randomized, double-blind, placebo-controlled, safety/efficacy trial | Group1: Acetaminophen 1 g q 6
Group 2:
NAC IV 0.5 g/h
Group 3:
Acetaminophen 1 g q6 + NAC 0.5 g/h
Group 4:
Acetaminophen 1.5 g q 6 + NAC 0.5 g/h | Placebo | 120 | Primary outcome: F2-IsoP biomarkers for lipid peroxidation.
Secondary outcome: vasospasm and brain ischemia as assessed by CTA/CTP or MRI DWI | John Oates,
NCT00585559 | Hemoglobin released from lysed RBCs oxidizes and generates protein radicals that induce lipid peroxidation. Metabolites of peroxidations (F2-isoprostanes) are potent vasoconstrictors. Acetaminophen can inhibit these metabolites and NAC can inhibit lipid peroxidation |
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| Neuroprotective drugs |
|
| Effects of tiopronin on 3-aminopropanal level and neurologic outcome after aneurysmal SAH | Randomized, double-blind, phase 2
bioavailability | Tiopronin | Placebo | 60 | Primary outcome: serum and CSF 3AP levels
Secondary outcomes:
12 month mRS, Barthel, Lawton, NIHSS, TICS
adverse events | E Sander Connolly,
NCT01095731 | 3AP is toxic metabolite produced during cerebral ischemia. It is neutralized by tiopronin |
| Lycopene following aneurysmal subarachnoid haemorrhage (LASH) | Randomized, double-blind, placebo-controlled, efficacy study | Lycopene 30 mg PO qd × 21 days | Placebo | 124 | Primary outcome: TCD vasospasm, duration of impaired autoregulation measured by TCD
Secondary Outcomes: LDL, oxy-LDL, CRP, circulating endothelial cells, endothelial progenitor cells | Karol Budohoski,
NCT00905931 | Lycopene is a natural antioxidant that may reduce vascular injury and inflammation and limit vasospasm |
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| Thrombolytics |
|
| Intraventricular tPA in the management of aneurysmal subarachnoid hemorrhage | Randomized, placebo-controlled, double-blind safety trail | tPA intraventricular q 12 h × 5 doses | Placebo administered q 12 h × 5 doses | 12 | Primary outcome: HCT rate and variance of ventricular and cisternal clot clearance
Secondary outcome: hemorrhagic complications, ventriculostomy-related infections, TCD vasospasm, CT angio vasospasm, symptomatic vasospasm, CSF cytokines and coagulation measurements, ICP, fever burden, volume of CSF drainage, 6-month GOSE and EuroQOL | Andreas Kramer,
NCT01098890 | Intraventricular TPA may accelerate clearance of IVH ameliorating vasospasm, hydrocephalus, and ICP |
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| Transfusion |
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| Effect of red blood cell transfusion on brain metabolism in patients with SAH | Open label safety/efficacy study in SAH patients with Hgb < 12.5 g/dL and DCI, high risk for vasospasm or angiographic vasospasm | Transfusion of 1 unit of packed RBC over 1 hour | NA | 48 | Primary outcome: percent of brain regions with low oxygen delivery before and 1 hour after transfusion
Secondary outcomes: relationship of oxygen delivery and angiographic vasospasm | Michael Diringer, NCT00968227 | Uses PET to assess the relationship between Hct and oxygen delivery in SAH patients |
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| Vasodilators |
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| Sildenafil for prevention of cerebral vasospasm (SIPCEVA) | Randomized, double-blind, placebo-controlled, safety and efficacy study | Tier 1: sildenafil 25 mg PO TID day 3–14 after SAH
Tier 2:
sildenafil 50 mg PO TID day 3–14 after SAH | Placebo | 18 | Primary outcome: New neurological deficit due to vasospasm up to 14 days after SAH
Secondary outcomes: TCD spasm, mortality, adverse drug effects, length of stay, discharge mRS | Andre Cerutti Franciscatto,
NCT01091870 | — |
| Safety study of dantrolene in SAH | Randomized, double-blind safety study | Dantrolene | Placebo | 30 | Primary outcome: tolerability, hyponatremia
Secondary outcomes: liver toxicity, hemodynamics, ICP, TCD, angiographic vasospasm treatments, 90-day GOS, mRS, and Barthel | Susanne Muehlschlegel,
NCT01024972 | Dantrolene is a muscle relaxant that may ameliorate vascular muscle tone and limit vasospasm |
| Safety and pharmacokinetic evaluation of nitrite for prevention of cerebral vasospasm | Randomized, single-blind, parallel assignment safety study | Tier 1:
sodium nitrite 32 nmol/kg/min
Tier 2:
sodium nitrite 48 nmol/kg/min
Tier 3:
sodium nitrite 64 nmol/kg/min | Placebo vehicle | 18 | Primary outcome: pharmacokinetics of 14-day sodium nitrite infusion
Secondary outcomes: safety and efficacy | Edward Oldfield,
NCT00873015 | — |
| Effects of prostacyclin infusion on cerebral vessels and metabolism in patients with subarachnoid hemorrhage | Randomized, placebo controlled, double-blind, parallel assignment, pharmacodynamics study | Tier 1:
prostacyclin 1 ng/kg/min day 5–10 after SAH
Tier 2:
prostacyclin 2 ng/kg/min day 5–10 after SAH | Placebo, IV infusion day 5–10 after SAH | 90 | Primary outcome: vasospasm measured by CT perfusion
Secondary outcomes: cerebral metabolism measured by microdialysis, 3-month GOS, clinical vasospasm, brain tissue oxygen, CT angio vasospasm, MAP, serum S100b | Rune Rasmussen, NCT01447095 | Prostacyclin may cause vasodilation and ameliorate vasospasm |
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| Hypertensive, hypervolemic therapy |
|
Induced hypertension for treatment of delayed cerebral ischemia after aneurysmal SAH
HIMALAIA | Randomized, Single blind safety/efficacy study of patients with SAH and DCI (clinically defined) | Induced hypertension with vasopressors and fluids for 48 hours | No induced hypertension | 240 | Primary outcome: mRS at 3 months
Secondary outcomes: proportion of treated patients who did not have clinical improvement of DCI symptoms within 24 hours, 30-day mortality, 3-month Barthel, SSQoL, hospital anxiety and depression scale, cognitive failures questionnaire, hospital complications, CTP results, medical costs | Arjen Slooter and Walter van den Bergh,
NCT01613235 | CBF measured in all patients using CTP at enrollment and 24–36 hours |
| Intensive management of pressure and volume expansion in patients with subarachnoid hemorrhage (IMPROVES) | Randomized, single-blind, factorial assignment | Tier 1: hypervolemia + conventional blood pressure
Tier 2: normovolemia + hypertension
Tier 3:
hypervolemia + hypertension | Normal volume, normal blood pressure | 20 | Primary outcome: achievement of hemodynamic goals in each group | Miriam Treggiari,
NCT01414894 | Though triple H is a common therapy, its safety and efficacy have not been well quantified |
|
| CSF diversion |
|
| EARLYDRAIN: outcome after early lumbar CSF: drainage in aneurysmal subarachnoid hemorrhage | Randomized, 2-arm controlled trial | Continuous lumbar CSF drainage of 120 mg qd × 7 d | Standard NICU care | 300 | Primary outcome: 6-month mRS
Secondary outcomes: 6-month mortality, angiographic vasospasm, TCD vasospasm, shunt insertion rate at 6 months | Bardutzky J,
NCT01258257 | Lumbar drainage to remove blood from the basal cisterns may limit delayed cerebral ischemia |
| Cerebrospinal fluid (CSF) drainage study | Randomized, open label, parallel assignment study of SAH patients requiring external ventricular drainage (EVD) | High volume CSF diversion (EVD at 5 mmHg) × 10 days | Conventional CSF diversion (EVD at 15 mm Hg), weaned at physician discretion | 20 | Primary outcome: 90-day mRS
Secondary Outcome: radiologic infarction, TCD or angiographic vasospasm, shunt placement, ventriculitis, discharge mRS, 90 day mini-mental status exam, length of stay | Giuseppe Lanzino,
NCT01420978 | More aggressive CSF drainage may improve brain microcirculation and perfusion and lead to better neurological outcomes |
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| Antiepileptics |
|
| Comparison of short duration levetiracetam to extended course for seizure prophylaxis after subarachnoid hemorrhage | Randomized, prospective, open label, parallel assignment, phase III, safety/efficacy study | Levetiracetam 1000 mg BID × 3 days | Levetiracetam 1000 mg BID × hospital stay | 460 | Primary outcome: In hospital seizures
Secondary outcome: Incidence of seizure after hospital discharge, adverse drug reactions, length of stay, cognitive and functional outcomes | Rajat Dhar,
NCT01137110 | Antiepileptics can have long-term cognitive side effects. A short course may be just as efficacious as prolonged use |
| Antiepileptic drugs and vascular risk markers | Randomized, open label, parallel assignment study | Tier 1: phenytoin 5 mg/kg/d divided in 2 doses
Tier 2: valproate 15 mg/kg/d divided in 3 doses
Tier 3: levetiracetam 1000-1500 mg/d divided in 2 doses | No drug intervention | 200 | Primary outcome: serum cholesterol, non-HDL cholesterol, HDL, lipoprotein a, CRP
Secondary outcome: acute seizures, late seizures, mRS at 8 and 16 weeks | Prema Kishna and Scott Mintzer,
NCT00774306 | Certain seizure medications may raise cholesterol levels and increase the risk of heart attack and stroke |
|
| Sedation |
|
| Effects of dexmedetomidine on inflammatory cytokines in patients with aneurysmal subarachnoid hemorrhage | Randomized, open label, parallel assignment efficacy study | Dexmedetomidine 0.2–1.5 mcg/kg/h | Propofol 5–80 mcg/kg/min | 10 | Primary outcome: serum and CSF cytokines over 48 hours
Secondary outcomes: sedative and analgesic requirements, RASS and CAM-ICU scores, length of stay, delayed cerebral ischemia, GOSE at discharge | Shaun Keegan and Brittany Woolf,
NCT01565590 | Dexmedetomidine may cause less inflammation over time than propofol |
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| Rehabilitation |
|
| Rehabilitation of patients after subarachnoid hemorrhage | Nonrandomized, open label, parallel assignment | Early multidisciplinary rehab and mobilization | No intervention | 160 | Primary outcome: 10-week GOS
Secondary outcome: 3–6 month and 12-month GOSE, functional independence measure, coma recovery scale, disability rating scale, High-level Mobility Assessment tool, pain score | Tanja Karic and Angelika Sorteberg,
NCT01656317 | Early rehab may reduce complications and improve physical and cognitive function after SAH |
|
| Blood pressure control |
|
| Safety and Efficacy Study of Clevidipine to Control Hypertension in Patients Admitted with Aneurysmal Subarachnoid Hemorrhage (CLASH) | Open label, safety, efficacy study, single group assignment (Phase 2) | Clevidipine IV 2–32 mg/h for 24–48 hours | NA | 20 | Primary: Blood pressure within target range | Panayiotis Varelas,
NCT00978822 | To assess how rapidly and safely Clevidipine can be used to control blood pressure in SAH patients. |
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| Other |
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| Cervical spinal cord stimulation for the prevention of cerebral vasospasm | Nonrandomized, open label | Spinal cord stimulation using MTS Trial System 3510 | NA | 12 | Primary outcome: cerebral vasospasm
Secondary outcome: adverse events | Konstantin Slavin, NCT00766844 | — |
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