Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials

Jiang, Bin; Ball, Robyn L.; Michel, Patrik; Jovin, Tudor G; Desai, Manisha; Eskandari, Ashraf; Naqvi, Zack; Wintermark, Max

doi:10.1161/strokeaha.117.016759

Cited by 2 publications

(4 citation statements)

References 15 publications

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“…Ethics approval was obtained from our local Institutional Review Board (IRB) and since this was a retrospective study, the IRB waived the need for patient consent. Ideally, this study would utilize the pooled trial data but since the complete trial data are unavailable, we compared the inclusion criteria of imaging biomarkers across trials through utilizing the published results and criteria from the MR CLEAN, ESCAPE, SWIFT PRIME, and EXTEND-IA trials ( Table 1 ) in combination with an independent registry of stroke imaging data [ 1 ]. Published trial results include the demographic and imaging biomarker inclusion criteria, number of patients in the treated and control arms, proportion of patients in each arm with a positive outcome, as well as number needed to treat (NNT).…”

Section: Methodsmentioning

confidence: 99%

“…Published trial results include the demographic and imaging biomarker inclusion criteria, number of patients in the treated and control arms, proportion of patients in each arm with a positive outcome, as well as number needed to treat (NNT). The previously characterized independent registry [ 1 ] includes baseline parenchymal, perfusion, and vascular imaging data of 612 acute ischemic stroke patients, as well as the time since symptom onset, demographic information, treatment course, and clinical outcomes of these patients. An interactive web application, available at https://neuroradiology.shinyapps.io/strokeimbio/ , can be used to explore this registry.…”

Section: Methodsmentioning

confidence: 99%

“…With an increasing amount of trial data becoming available, straightforward statistical approaches and methodologies are poised to help clinical researchers best utilize existing trial data to inform the design of upcoming trials. For example, there has been debate regarding the use of advanced imaging biomarkers in recent positive acute stroke clinical trials [ 1 ]. Screening for advanced imaging biomarkers is expensive and it is critical that trials are designed to benefit the greatest number of patients.…”

Section: Introductionmentioning

confidence: 99%

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A statistical approach to identify optimal inclusion criteria: An application to acute stroke clinical trials

Ball

Jiang

Desai

et al. 2019

Contemporary Clinical Trials Communications

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Purpose To develop a statistical approach that compares patient selection strategies across clinical trials and apply this approach to acute ischemic stroke clinical trials to identify the optimal inclusion criteria. Methods We developed a statistical approach that compares the number needed to treat to achieve one success (NNT) along with the number needed to screen to achieve one success (NNS) and assesses if there are significant differences in inclusion criteria, treatment course, and clinical outcome among patients that may have been included/excluded in the trials. We applied this approach to the study population from four recent positive acute stroke clinical trials: MR CLEAN, EXTEND-IA, ESCAPE, and SWIFT PRIME, applying published trial criteria to an independent registry of 612 acute stroke patients, since we did not have access to the complete trial data. Results Although reported NNT were similar for EXTEND-IA, SWIFT PRIME and ESCAPE, and somewhat higher for MR CLEAN, NNS varied across the trials from 21 for EXTEND-IA, 27 for MR CLEAN, to 46 for ESCAPE and 64 for SWIFT PRIME, reflecting less and more stringent inclusion criteria, respectively. Although there were significant differences in imaging biomarkers and other clinical characteristics among patients that may have been included/excluded in the trials, these differences did not translate to significant differences in treatment course or clinical outcomes. Conclusions Our study proposes a robust statistical approach that can be applied to a larger pooled trial dataset, if made available, to objectively compare across clinical trials and inform inclusion criteria of future trials. Pooled analysis of the acute stroke trial data is needed to determine which imaging biomarker inclusion criteria are critical and which may be relaxed. If this procedure were applied across the pooled trial data, it could decrease costs and refine the design of future trials to be the most efficacious for the greatest number of patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A statistical approach to identify optimal inclusion criteria: An application to acute stroke clinical trials

Ball

Jiang

Desai

et al. 2019

Contemporary Clinical Trials Communications

Self Cite

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“…A total of 76 patients with AIS who were treated at Southwest Hospital (Chongqing, China) between January 2018 and April 2018 were selected as the case group (IS group) based on AIS guidelines (18). The inclusion criteria were as follows: i) Brain CT/MRI examination revealing ischemic lesions; ii) numbness or weakness present in one limb or face and speech difficulty; and iii) sudden onset of stroke, which necessitated emergency admission to the Southwest Hospital.…”

Section: General Informationmentioning

confidence: 99%

miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

Yang

Wang³

et al. 2020

Exp Ther Med

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The protective role of microRNA (miR)-135b in cerebral neurons has been previously identified. However, to the best of our knowledge, the involvement of miR-135b in acute ischemic stroke has yet to be elucidated. The present study aimed to investigate the expression profile of miR-135b in peripheral blood obtained from patients with acute ischemic stroke. A total of 76 patients with acute ischemic stroke were selected as the case group, which included 33 cases of aorta atheromatous plague, 19 cases of cardioembolism, 16 cases of small arterial occlusion and 8 cases with unknown causes. In addition, 60 healthy subjects were selected as the control group. Reverse transcription-quantitative PCR was used to measure the expression of miR-135b in the peripheral blood of the patients. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the severity of acute ischemic stroke. The relationship between miR-135b levels and acute stroke was subsequently analyzed. The expression of miR-135b in the peripheral blood of the case group was found to be significantly higher compared with that in the control group. By contrast, the expression levels of miR-135b in the case group did not differ significantly between the different etiology types of acute ischemic stroke. In addition, a significant positive correlation was observed between levels of miR-135b expression and NIHSS scores. Further analysis demonstrated that hypertension, hyperglycemia, platelet count, international normalized ratio and miR-135b were risk factors for acute ischemic stroke. Based on bioinformatics analysis, a conserved binding site for miR-135b was identified in the 3'-untranslated region of the transient receptor potential cation channel subfamily C member 6 (TRPC6). Dual luciferase reporter and western blot analysis showed that TRPC6 was a target gene of miR-135b. In conclusion, data from the present study suggest that elevated expression of miR-135b in the peripheral blood of patients with acute ischemic stroke is closely associated with disease severity.

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Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials

Cited by 2 publications

References 15 publications

A statistical approach to identify optimal inclusion criteria: An application to acute stroke clinical trials

A statistical approach to identify optimal inclusion criteria: An application to acute stroke clinical trials

miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

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