Methodological Quality of Animal Studies of Neuroprotective Agents Currently in Phase II/III Acute Ischemic Stroke Trials

Maria Philip; Michael Benatar; Marc Fisher; Sean I. Savitz

doi:10.1161/strokeaha.108.524330

THE MISMATCH BETWEEN CEREBRAL BLOOD FLOW AND TMAX PREDICTS THE QUALITY OF COLLATERALS IN ACUTE ISCHEMIC STROKE

10.26226/morressier.58e389b1d462b80292385155 ◽

2017 ◽

Author(s):

Ivana Galinovic

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Ischemic Stroke ◽

Acute Ischemic Stroke

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Abstract 115: Improving Door-to-Needle Times in Acute Ischemic Stroke: Interim Findings From Target: Stroke Phase II

Stroke ◽

10.1161/str.47.suppl_1.115 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Gregg C Fonarow ◽

Margueritte Cox ◽

Eric E Smith ◽

Jeffrey L Saver ◽

Mathew J Reeves ◽

...

Keyword(s):

Ischemic Stroke ◽

Phase I ◽

Acute Ischemic Stroke ◽

Phase Ii ◽

Best Practice ◽

Patient Characteristics ◽

Clinical Decision ◽

Absolute Difference ◽

First Year ◽

Rate Of Increase

Background: The benefits of intravenous tPA in acute ischemic stroke are time-dependent with guidelines recommending a door-to-needle (DTN) time of ≤60 minutes. The implementation of Target: Stroke Phase I in 2010 was associated with an increase in the proportion of patients with DTN times ≤60 minutes in the US from 28.9% in 2009 to 51.0% in 2013. This study aims to assess whether these improvements in DTN times could be maintained or further improved since the launch of Target: Stroke Phase II in Q2 2014. Methods: Target: Stroke Phase II identified and disseminated additional best practice strategies, provided updated clinical decision support tools, and set new hospital recognition goals. Rates of DTN times ≤60 minutes were compared during final 4 quarters of Phase I (Q4 2012-Q3 2013) vs. Phase II (Q2 2014-Q1 2015) and overall by linear weighted regression. Results: There were 99,176 intravenous tPA treated patients from 1228 GWTG-Stroke hospitals. Patient characteristics were similar during Phase I and II. Median DTN time significantly declined from the last 4 quarters of Phase I to the first 4 quarters of Phase II: 61 minutes (IQR 47-81) to 57 minutes (IQR 43-74) (P<0.0001). The % of patients with DTN times ≤60 minutes increased from last 4 quarters of Phase I to Phase II: 49.7% to 58.5%, absolute difference +8.8%, (P<0.0001). The % of patients with DTN times ≤45 minutes also increased from Phase I to Phase II: 22.0% to 29.2%, absolute difference +7.2%, (P<0.0001). The estimated annual rate of increase in patients with DTN times ≤60 minutes was 0.6% per year pre-Target Stroke, 5.6% per year during Phase I, and 8.6% in the first year of Phase II (P<0.0001) (Figure). Conclusions: The timeliness of tPA administration is continuing to improve in GWTG-Stroke hospitals participating in Target: Stroke Phase II. Nevertheless, ongoing quality improvement efforts will be required to meet the goals of ≥75% of patients with DTN times ≤60 minutes and ≥50% of patients with DTN times ≤ 45 minutes.

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Neuroprotective agents in Acute Ischemic Stroke—A Reality Check

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.11.041 ◽

2019 ◽

Vol 109 ◽

pp. 2539-2547 ◽

Cited By ~ 4

Author(s):

Luxitaa Goenka ◽

Chakradhara Rao Uppugunduri Satyanarayana ◽

Suresh Kumar S ◽

Melvin George

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Neuroprotective Agents ◽

Reality Check

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Potential role of neuroprotective agents in the treatment of patients with acute ischemic stroke

Current Treatment Options in Cardiovascular Medicine ◽

10.1007/s11936-003-0033-9 ◽

2003 ◽

Vol 5 (6) ◽

pp. 441-449 ◽

Cited By ~ 25

Author(s):

Bruce Ovbiagele ◽

Chelsea S. Kidwell ◽

Sidney Starkman ◽

Jeffrey L. Saver

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Potential Role ◽

Neuroprotective Agents

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Intra-Arterial Bone Marrow Mononuclear Cells (BM-MNCS) Transplantation in Acute Ischemic Stroke (IBiS Trial): Protocol of a Phase II, Randomized, Dose-Finding, Controlled Multicenter Trial

International Journal of Stroke ◽

10.1111/ijs.12520 ◽

2015 ◽

Vol 10 (7) ◽

pp. 1149-1152 ◽

Cited By ~ 27

Author(s):

Francisco Moniche ◽

Irene Escudero ◽

Elena Zapata-Arriaza ◽

María Usero-Ruiz ◽

María Prieto-León ◽

...

Keyword(s):

Bone Marrow ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Phase Ii ◽

Mononuclear Cells ◽

Multicenter Trial ◽

Dose Finding ◽

Bone Marrow Mononuclear Cells ◽

Trial Protocol

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Abstract W P287: Does Comprehensive Stroke Certification Demonstrate a Significant Effect on Volume and Quality of Care?

Stroke ◽

10.1161/str.45.suppl_1.wp287 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Laurie Paletz ◽

Shlee Song ◽

Nili Steiner ◽

Betty Robertson ◽

Nicole Wolber ◽

...

Keyword(s):

Ischemic Stroke ◽

Quality Of Care ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Turnaround Time ◽

Joint Commission ◽

Stroke Patients ◽

Number Of Patients ◽

The Impact

Introduction/Background information: At the onset of acute stroke symptoms, speed, capability, safety and skill are essential-lost minutes can be the difference between full recoveries, poor outcome, or even death. The Joint Commission's Certificate of Distinction for Comprehensive Stroke Centers recognizes centers that make exceptional efforts to foster better outcomes for stroke care. While many hospitals have been surveyed, Cedars Sinai was the 5 th hospital in the nation to receive this certification. Researchable question: Does Comprehensive stroke certification (CSC) demonstrate a significant effect on volume and quality of care? Methods: We assembled a cross-functional, multidisciplinary expert team representing all departments and skill sets involved in treating stroke patients. We carefully screened eligible patients with acute ischemic stroke We assessed the number of patients treated at Cedars-Sinai with IV-T-pa t 6 months before and then 6 months after CSC and the quality of their care including medical treatment and door to needle time. Results: In the 6 months prior to Joint Commissions Stroke Certification we treated 20 of 395acute stroke patients with t-PA with an average CT turnaround time of 31±19minutes and an average Door to needle time (DTNT) of 68±32minutes. In the 6 months since Joint Commission Stroke Certification we have increased the number of acute stroke patients treated by almost double. There were 37 out of 489(P=0.02, Chi Square) patients treated with IV t-PA with an average CT turnaround time of 22±7minutes (p=0.08, t-test, compared to pre-CSC) and an average DTNT of 61± 23minutes (not different than pre-CSC). Conclusion: We conclude that Joint Commission Certification for stroke was associated with an increased rate of treatment with IV rt-PA in acute ischemic stroke patients. We were not able to document an effect on quality of care. Further studies of the impact of CSC certification are warranted.

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Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20952011 ◽

2020 ◽

Vol 41 (1) ◽

pp. 14-30 ◽

Cited By ~ 1

Author(s):

Mark P Maskery ◽

Christian Holscher ◽

Stephanie P Jones ◽

Christopher I Price ◽

W David Strain ◽

...

Keyword(s):

Clinical Trials ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Scoping Review ◽

Clinical Studies ◽

Neuroprotective Agents ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Retrospective Database

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.

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