Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial

Sheth, Kevin N; Elm, Jordan; Molyneaux, Bradley J.; Hinson, Holly E.; Beslow, Lauren A.; Sze, Gordon; Ostwaldt, Ann-Christin; Zoppo, Gregory J. del; Simard, J. Marc; Jacobson, Sven; Kimberly, W. Taylor

doi:10.1016/s1474-4422(16)30196-x

Cited by 205 publications

(228 citation statements)

References 31 publications

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“…42 Blockade of SUR1-TRPM4 also results in significant reductions in ischemia-associated MMP-9. 67–69 As such, SUR1-TRPM4 may contribute to cellular, ionic and vasogenic edema following aSAH. Studies of SUR1-TRPM4 confirm significant upregulation of channel expression following aSAH in both humans and rats.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Mechanisms of Global Cerebral Edema Formation in Aneurysmal Subarachnoid Hemorrhage

et al. 2016

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Section: Molecular Mechanismsmentioning

confidence: 99%

Mechanisms of Global Cerebral Edema Formation in Aneurysmal Subarachnoid Hemorrhage

et al. 2016

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“…However, there are a number of promising therapies, such as NA-1, glyburide, activated protein C, and uric acid, that have recently passed Phase 2 clinical trials. 19,40,64,85 It is hypothesized that the failure of many neuroprotective strategies is due to the fact that agents only target 1 point in a mechanistic pathway. Hypothermia, however, is a promising therapy that exhibits a wide range of cel-lular mechanisms.…”

Section: Prehospital Delivery Methodsmentioning

confidence: 99%

Neuroprotective delivery platforms as an adjunct to mechanical thrombectomy

Babadjouni¹,

Walcott

Liu³

et al. 2017

FOC

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Despite the success of numerous neuroprotective strategies in animal and preclinical stroke models, none have effectively translated to clinical medicine. A multitude of influences are likely responsible. Two such factors are inefficient recanalization strategies for large vessel occlusions and suboptimal delivery methods/platforms for neuroprotective agents. The recent endovascular stroke trials have established a new paradigm for large vessel stroke treatment. The associated advent of advanced mechanical revascularization devices and new stroke technologies help address each of these existing gaps. A strategy combining effective endovascular revascularization with administration of neuroprotective therapies is now practical and could have additive, if not synergistic, effects. This review outlines past and current neuroprotective strategies assessed in acute stroke trials. The discussion focuses on delivery platforms and their potential applicability to endovascular stoke treatment.

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“…22 Finally, a recent meta-analysis of 10 randomized trials showed a higher rate of independence (OR 1.56, 95% CI 1.12-2.16), but the effect was more limited than those of other treatments (e.g., TPA). 130 Citicoline is in clinical use in a number of countries, including Argentina, Austria, Chile, Indonesia, Mexico, Portugal, Thailand, and Venezuela. 18 …”

Section: Antioxidant Agentsmentioning

confidence: 99%

“…131 The GAMES-RP (glyburide on brain swelling after large hemispheric infarction) Phase II trial evaluated 86 patients with a primary outcome of mRS score 0-4 at 90 days in patients who did not undergo a decompressive craniectomy. 130 No difference in primary composite outcome was seen, and the trial was terminated early because of loss of funding.…”

Section: Glyburide To Preserve Cerebral Function After Injurymentioning

confidence: 99%

Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke

Karsy¹,

Brock²,

Guan³

et al. 2017

FOC

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Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade. Results of historical research trials involving N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonists, clomethiazole, antioxidants, citicoline, nitric oxide, and immune regulators have laid the groundwork for current progress. In addition, more recent studies involving therapeutic hypothermia, magnesium, albumin, glyburide, uric acid, and a variety of other treatments have provided more options. The use of neuroprotective agents in combination or with existing thrombolytic treatments may be one of many exciting areas of further development. Although past trials of neuroprotective agents in ischemic stroke have been limited, significant insights into mechanisms of stroke, animal models, and trial design have incrementally improved approaches for future therapies.

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Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial

Cited by 205 publications

References 31 publications

Mechanisms of Global Cerebral Edema Formation in Aneurysmal Subarachnoid Hemorrhage

Mechanisms of Global Cerebral Edema Formation in Aneurysmal Subarachnoid Hemorrhage

Neuroprotective delivery platforms as an adjunct to mechanical thrombectomy

Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke

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