Acute Stroke Trials Research Articles

Ethical Considerations during the Informed Consent Process for Acute Ischemic Stroke in International Clinical Trials.

We sought to investigate the experiences of researchers in existing active-control trials in acute ischemic stroke comparing investigational therapy to tissue plasminogen activator (tPA) in order to identify the approaches and challenges in obtaining informed consent. Out of 401 articles evaluated, 14 trials met inclusion criteria. Trial representatives were contacted to complete a survey concerning the consent process. None of the 14 trials published materials related to the informed consent process. Trials with 75% to 100% of patients directly consented had shorter door-to-treatment (DTT) times than trials that directly consented less than 50% of patients. Trials that had translators available (for recruiting participants who were not native speakers in the local language) and translated consent documents had longer DTT times. The study findings suggest that differences in the standards of informed consent internationally may allow more patients with moderate strokes to provide direct consent without delaying DTT time. Future trials should emphasize transparency to the public and scientific community in the informed consent process.

Plasma Soluble Dipeptidyl Peptidase-4 and Risk of Major Cardiovascular Events After Ischemic Stroke

Recent studies have suggested that plasma soluble dipeptidyl peptidase-4 (sDPP4) have important physiologic effects, which may influence the prognosis of ischemic stroke. Our study aimed to examine the relationship between plasma sDDP4 levels and long-term clinical outcomes among patients with acute ischemic stroke. Secondary analysis was conducted among 3,564 participants (2,270 men and 1,294 women) from the China Antihypertensive Trial in Acute Ischemic Stroke with baseline measurement of plasma sDPP4 levels. We evaluated the associations between plasma sDPP4 levels and 2-year clinical outcomes using logistic regression and Cox regression models. We further investigated the predictive utility of sDPP4 by calculating net reclassification index and integrated discrimination improvement. The highest plasma sDPP4 quartile was associated with lower risk of cardiovascular events (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.45-0.87), recurrent stroke (HR 0.70, 95% CI 0.49-0.99), all-cause mortality (HR 0.62, 95% CI 0.44-0.87), stroke-specific mortality (HR 0.65, 95% CI 0.44-0.94), and poor functional outcomes (odds ratio 0.66, 95% CI 0.53-0.82) at 2 years compared with the lowest sDPP4 category in multivariable models. The addition of plasma sDPP4 to conventional risk factors model significantly improved risk prediction of all outcomes. In this study, we found that higher plasma sDPP4 levels in patients with acute ischemic stroke were associated with decreased risks of cardiovascular events, recurrent stroke, all-cause mortality, and poor functional outcomes after ischemic stroke. These findings suggest that plasma sDPP4 may be a potential prognostic marker for initial risk stratification in patients with acute ischemic stroke.

Plasma Thrombomodulin Levels and Ischemic Stroke: A Population-Based Prognostic Cohort Study.

Thrombomodulin has been suggested to be implicated in ischemic stroke because of its anticoagulant, anti-inflammatory, and cytoprotective properties. We aimed to investigate the associations of plasma thrombomodulin levels with clinical outcomes after ischemic stroke in a multicenter prognostic cohort study. Our multicenter prognostic cohort study included 3,532 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death and major disability (modified Rankin Scale [mRS] score ≥3) at 3 months after ischemic stroke. Secondary outcomes included major disability (mRS score 3-5), vascular events, and the ordered 7-level categorical score of the mRS. During 3 months of follow-up, 867 participants experienced the primary outcome. After multivariate adjustment, the adjusted odds ratios or hazard ratios associated with the highest quartile of plasma thrombomodulin were 0.75 (95% CI 0.59-0.97; p trend = 0.029) for the primary outcome, 0.73 (95% CI 0.56-0.94; p trend = 0.028) for major disability, and 0.80 (95% CI 0.42-1.51; p trend = 0.232) for vascular events. In addition, a significantly better shift in the distribution of the mRS score was observed with higher thrombomodulin quartiles (p trend = 0.005). A multivariable-adjusted spline regression model showed a linear relationship between plasma thrombomodulin and the risk of primary outcome (p for linearity = 0.027). Subgroup analyses further confirmed these associations. Increased plasma thrombomodulin levels at baseline were associated with decreased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting a protective role of thrombomodulin in the development of ischemic stroke. Further studies from various populations are needed to replicate our findings.

Improving Visualization Methods of Utility-Weighted Disability Outcomes for Stroke Trials.

BackgroundThe modified Rankin Scale (mRS) is the most common endpoint in acute stroke trials, but its power is limited when analyzed dichotomously and its indication of effect size is challenging to interpret when analyzed ordinally. To address these issues, the utility-weighted-mRS (UW-mRS) has been developed as a patient-centered, linear scale. However, appropriate data visualizations of UW-mRS results are needed, as current stacked bar chart displays do not convey crucial utility-weighting information.Design/MethodsTwo UW-mRS display formats were devised: (1) Utility Staircase charts, and (2) choropleth-stacked-bar-charts (CSBCs). In Utility Staircase displays, mRS segment height reflects the utility value of each mRS level. In CSBCs, mRS segment color intensity reflects the utility of each mRS level. Utility Staircase and CSBC figures were generated for 15 randomized comparisons of acute ischemic/hemorrhagic stroke therapies, including fibrinolysis, endovascular reperfusion, blood pressure moderation, and hemicraniectomy. Display accuracy in showing utility outcomes was assessed with the Tufte-lie-factor and ease-of-use assessed by formal ratings completed by a panel of 4 neurologists and emergency physicians and one nurse-coordinator.ResultsThe Utility Staircase and CSBC displays rapidly conveyed patient-centered valuation of trial outcome distributions not available in conventional ordinal stacked bar charts. Tufte-lie-factor (LF) scores indicated “substantial distortion” of utility-valued outcomes for 93% (14/15) of conventional stacked bar charts, vs. “no distortion” for all Utility Staircase and CSBC displays. Clinician ratings on the Figural Display Questionnaire indicated that utility information encoded in row height (Utility Staircase display) was more readily assimilated than that conveyed in segment hue intensity (CSBC), both superior to conventional stacked bar charts.ConclusionsUtility Staircase displays are an efficient graphical format for conveying utility weighted–modified Rankin Scale primary endpoint results of acute stroke trials, and choropleth-stacked-bar-charts a good alternative. Both are more accurate in depicting quantitative, health-related quality of life results and preferred by clinician users for utility results visualization, compared with conventional stacked bar charts.

Comparison of Bayesian vs Frequentist Adaptive Trial Design in the Stroke Hyperglycemia Insulin Network Effort Trial

Bayesian adaptive trial design has the potential to create more efficient clinical trials. However, a barrier to the uptake of bayesian adaptive designs for confirmatory trials is limited experience with how they may perform compared with a frequentist design. To compare the performance of a bayesian and a frequentist adaptive clinical trial design. This prospective cohort study compared 2 trial designs for a completed multicenter acute stroke trial conducted within a National Institutes of Health neurologic emergencies clinical trials network, with individual patient-level data, including the timing and order of enrollments and outcome ascertainment, from 1151 patients with acute stroke and hyperglycemia randomized to receive intensive or standard insulin therapy. The implemented frequentist design had group sequential boundaries for efficacy and futility interim analyses at 90 days after randomization for 500, 700, 900, and 1100 patients. The bayesian alternative used predictive probability of trial success to govern early termination for efficacy and futility with a first interim analysis at 500 randomized patients and subsequent interims after every 100 randomizations. The main outcome was the sample size at end of study, which was defined as the sample size at which each of the studies stopped accrual of patients. Data were collected from 1151 patients. As conducted, the frequentist design passed the futility boundary after 936 participants were randomized. Using the same sequence and timing of randomization and outcome data, the bayesian alternative crossed the futility boundary approximately 3 months earlier after 800 participants were randomized. Both trial designs stopped for futility before reaching the planned maximum sample size. In both cases, the clinical community and patients would benefit from learning the answer to the trial's primary question earlier. The common feature across the 2 designs was frequent interim analyses to stop early for efficacy or for futility. Differences between how these analyses were implemented between the 2 trials resulted in the differences in early stopping.

Serum Dickkopf-1 levels and poststroke depression in ischemic stroke patients

BackgroundSerum Dickkopf-1 (Dkk-1) levels are associated with poor ischemic stroke prognosis, although their impact on poststroke depression (PSD) remains unclear. This study aimed to examine the association between serum Dkk-1 levels and PSD. MethodsSerum Dkk-1 levels were measured in 564 patients with ischemic stroke who participated in the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The patients' depression status at 3 months after stroke was assessed using the Hamilton Rating Scale for Depression (HRSD-24). The HRSD score cutoff point for the diagnosis of depression was ≥8. ResultsA total of 224 (39.72%) patients were categorized as having PSD 3 months after ischemic stroke. After adjusting for potential confounders, including age, sex, and other important covariates, elevated Dkk-1 levels were associated with an increased risk of PSD (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.14–3.22; Ptrend = 0.037). Similarly, each standard deviation (SD) increase in log-transformed Dkk-1 levels was associated with a 24% increased risk of PSD (OR, 1.24; 95% CI, 1.03–1.49; P = 0.025). Subgroup analyses further confirmed the significant associations between Dkk-1 levels and PSD. ConclusionHigher serum Dkk-1 levels at baseline are independently associated with an increased risk of PSD at 3 months after stroke, suggesting that Dkk-1 levels may be a promising prognostic biomarker for PSD. LimitationsThis study measured serum Dkk-1 levels only in the acute phase of stroke not in different phases; therefore, the relationship between dynamic changes in Dkk-1 levels and PSD could not be evaluated.

May Literature Synopsis

May Literature Synopsis

Soluble TREM2 is associated with death and cardiovascular events after acute ischemic stroke: an observational study from CATIS

BackgroundSoluble triggering receptor expressed on myeloid cells 2 (sTREM2), which reflects microglia activation, has been reported closely associated with neuronal injury and neuroinflammation. We aimed to prospectively investigate the associations between plasma sTREM2 and clinical outcomes in acute ischemic stroke (AIS) patients.MethodsStudy participants were from the China Antihypertensive Trial in Acute Ischemic Stroke, plasma sTREM2 levels in the acute phase of AIS were measured in 3285 participants. The study outcomes were death, cardiovascular events and severe disability at 1 year after AIS. Cox proportional hazards models or logistic regression models were performed to examine the associations of plasma sTREM2 and clinical outcomes.ResultsAfter 1-year follow-up, 288 participants (8.8%) experienced cardiovascular events or died. Multivariable-adjusted hazard ratios or odds ratios (95% confidence intervals) for the highest quartile of sTREM2 were 1.57 (1.11–2.21) for the composite outcome of death and cardiovascular events, 1.68 (1.09–2.60) for death, and 1.53 (1.08–2.18) for death or severe disability compared to the lowest quartile. Moreover, incorporation sTREM2 into traditional risk factors model significantly improved risk prediction of the composite outcome of death and cardiovascular events as evidenced by net reclassification index and integrated discrimination improvement (all p values < 0.05). There were joint effects of sTREM2 and galectin-3 on death and cardiovascular events. Participants with simultaneous elevation of sTREM2 and galectin-3 levels had the highest risk of the composite outcome of death and cardiovascular events.ConclusionsElevated sTREM2 levels were independently associated with increased risks of death and cardiovascular events after AIS.

Association Between Plasma L-Carnitine and Cognitive Impairment in Patients with Acute Ischemic Stroke.

L-carnitine has been shown to exert neuroprotective effects on cerebral ischemia, mainly by improving mitochondrial function and reducing inflammation. L-carnitine supplementation has also been promoted to enhance cognitive function. However, the relationship between L-carnitine and cognitive impairment after ischemic stroke has seldom been studied. We aimed to evaluate the association between plasma L-carnitine and poststroke cognitive impairment. The study sample population was drawn from the China Antihypertensive Trial in Acute Ischemic Stroke. Plasma L-carnitine were measured at baseline in 617 patients with ischemic stroke using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3-month follow-up after ischemic stroke. Plasma L-carnitine were inversely associated with cognitive impairment at 3 months after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartiles of L-carnitine was 0.60 (0.37, 0.98; p for trend = 0.04). Each 1-SD increase in log-transformed L-carnitine concentration was significantly associated with a 15% (95% CI: 1%, 29%) reduction in the risk of cognitive impairment after stroke. The addition of L-carnitine to the model including conventional risk factors significantly improved the risk reclassification for cognitive impairment (net reclassification improvement: 17.9%, integrated discrimination improvement: 0.8%; both p < 0.05). Furthermore, joint effects of L-carnitine and inflammation markers were observed, and patients with higher L-carnitine and a lower inflammatory status simultaneously had the lowest risk of poststroke cognitive impairment. The present study provided prospective evidence on the inverse association between plasma L-carnitine and cognitive impairment after ischemic stroke.

Getting the Most out of Consent: Patient-Centered Consent for an Acute Stroke Trial.

Informed consent for clinical trials in acute stroke is characterized by challenges related to urgency, cognitive impairment, and geographical separation. Context-appropriate approaches are needed for this setting. We conducted a mixed-methods project involving focus groups and interviews as well as collaboration with a patient advisory panel and a central institutional review board (CIRB) to design and implement a patient-driven consent process for a multicenter trial incorporating adaptive randomization. Remote consent was recognized as challenging but acceptable. Adaptive randomization was viewed positively, but significant potential for misunderstanding was appreciated. Collaboration between the patient advisory panel and the CIRB resulted in a shortened, more patient-centered consent form that was approved at all sites with few modifications. An information sheet was developed as a resource for patients and surrogates after enrollment. Collaboration between investigators, patient partners, and a CIRB can facilitate innovation and implementation of patient-centered, context-appropriate consent strategies.

Timely and Appropriate Administration of Inhaled Argon Provides Better Outcomes for tMCAO Mice: A Controlled, Randomized, and Double-Blind Animal Study.

Inhaled argon (iAr) has shown promising therapeutic efficacy for acute ischemic stroke and has exhibited impressive advantages over other inert gases as a neuroprotective agent. However, the optimal dose, duration, and time point of iAr for acute ischemic stroke are unknown. Here, we explored variable iAr schedules and evaluated the neuroprotective effects of acute iAr administration on lesion volume, brain edema, and neurological function in a mouse model of cerebral ischemic/reperfusion injury. Adult ICR (Institute of Cancer Research) mice were randomly subjected to sham, moderate (1.5h), or severe (3h) transient middle cerebral artery occlusion (tMCAO). One hour after tMCAO, the mice were randomized to variable iAr protocols or air. General and focal deficit scores were assessed during double-blind treatment. Infarct volume, overall recovery, and brain edema were analyzed 24h after cerebral ischemic/reperfusion injury. Compared with those in the tMCAO-only group, lesion volume (p < 0.0001) and neurologic outcome (general, p < 0.0001; focal, p < 0.0001) were significantly improved in the group administered iAr 1h after stroke onset (during ischemia). Short-term argon treatment (1 or 3h) significantly improved the infarct volume (1 vs. 24h, p < 0.0001; 3 vs. 24h, p < 0.0001) compared with argon inhalation for 24h. The concentration of iAr was confirmed to be a key factor in improving focal neurological outcomes relative to that in the tMCAO group, with higher concentrations of iAr showing better effects. Additionally, even though ischemia research has shown an increase in cerebral damage proportional to the ischemia time, argon administration showed significant neuroprotective effects on infarct volume (p < 0.0001), neurological deficits (general, p < 0.0001; focal, p < 0.0001), weight recovery (p < 0.0001), and edema (p < 0.0001) in general, particularly in moderate stroke. Timely iAr administration during ischemia showed optimal neurological outcomes and minimal infarct volumes. Moreover, an appropriate duration of argon administration was important for better neuroprotective efficacy. These findings may provide vital guidance for using argon as a neuroprotective agent and moving to clinical trials in acute ischemic stroke.

Abstract TP186: Heterogeneity Of Endovascular Treatment Effect: A Comparison Of Subgroup Identification Methods In Acute Stroke Trials

Background: Trials’ data are increasingly re-analyzed to identify treatment effect heterogeneity: that is, subgroups of patients who have either enhanced or adverse effects in a trial. This study investigates the robustness of subgroup identification methods in an acute stroke trial. Methods and Analysis: The Model-based recursive partitioning (MOB), Stochastic Subgroup Identification based on Differential Effects Search (Stochastic SIDEScreen), and Virtual Twin (VT) methods would be used to detect heterogeneity in Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Results: In the ESCAPE trial, patients in the intervention group had a higher rate of functional independence (90-day mRS 0-2) than those in the control group (OR=2.6; p&lt;0.001, and 95% CI=1.7–3.8). The three methods identified patients with differential treatment effects. The MOB identified 2-terminal subgroups, with the NIHSS &gt; 11 group showing a significant treatment effect (OR=3.67; p&lt;0.001 and 95% CI=2.11–6.40), while the subgroup of with a maximum NIHSS score of 11 did not (OR=1.63; p=0.463 and 95% CI=0.44–6.05). The stochastic SIDEScreen identified 4-terminal subgroups, but the group of patients with NIHSS greater than 9 and older than 54 years had a significant treatment effect (OR=4.92; p&lt;0.001, and 95% CI= 2.66–9.10). Other three subgroups, like patients with a maximum NIHSS score of 9 and older than 54 years (OR=2.17, p=0.34, and 95% CI=0.44–10.65), did not have a significant treatment effect. VT identified 6-terminal subgroups; the subgroup consisting of patients older than 56 years and NIHSS &gt; 11 had significant treat effect (OR=5.11; p&lt;0.001 and 95% CI=2.68–9.73). As other renaming 4 subgroups, the subgroup consisting of younger patients and with a maximum NIHSS score of 11 did not show a treatment effect (OR=1.60, p=0.64, and 95% CI=0.39–6.30). Conclusion: Data-driven subgroup identification methods provide insight into the heterogeneity of treatment effects in acute stroke trials. Information about the identified subgroups might inform the development of clinical practice guidelines for acute stroke management.

Abstract WP7: Critical Importance Of Enrollment Hours For Successful Recruitment In Acute Stroke Trials

Introduction: Recruitment into hyperacute stroke trials is challenging but ultimately depends on on-call availability of treating investigators, study coordinators, and pharmacists. These data may not be considered in initial decision-making for site selection and estimates of site recruitment are frequently based upon registry data from sites that includes all clinical cases. Hypothesis: Site recruitment on a per month basis is associated with time open for enrollment. Methods: We surveyed all Multi-arm Optimization of Stroke (MOST) trial centers open for enrollment to determine which were open for trial recruitment during business hours during Monday through Friday only, business hours 7 days a week, extended hours beyond business hours, or 24 hours/7 days a week. We also surveyed about pharmacy availability. Descriptive statistics were used to compare the average monthly enrollment by survey responses. Results: Sites open for enrollment only during business hours, Monday through Friday recruited at a rate of 0.14 participants per month compared to 0.36 per month for sites that enroll 7 days a week (see graphic). Restriction of pharmacy availability to business hours Monday through Friday was associated with decreased recruitment rate as well. Conclusions: Ability to recruit trial participants 7 days a week should be the standard for site selection, successful acute stroke trial recruitment, and estimates of needed sites. Methods to increase financial support for hours outside of week-day business hours is a potential method to enhance recruitment into acute stroke trials.

Advances in Stroke: Stroke in Women.

Advances in Stroke: Stroke in Women.

TACTICS - Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship: evaluating the effectiveness of an ‘implementation intervention’ in providing better patient access to reperfusion therapies: protocol for a non-randomised controlled stepped wedge cluster trial in acute stroke

IntroductionStroke reperfusion therapies, comprising intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), are best practice treatments for eligible acute ischemic stroke patients. In Australia, EVT is provided at few, mainly metropolitan,...

Abstract 3: Higher Pre-stroke Physical Activity Is Associated With Fewer Post-stroke Depressive Symptoms In Patients Treated With Citalopram As Compared To Placebo

Introduction: Post-stroke depression affects one in three stroke patients and is associated with increased mortality and disability. Physical activity (PA) has been associated with fewer depressive symptoms after stroke, however, the long-term effect of pre-stroke PA and how Selective Serotonin Reuptake Inhibitors may affect this association is unknown. Methods: The study was conducted as a secondary analysis of data from The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS) trial, where consecutive non-depressed acute ischemic stroke patients were randomized to Citalopram 20 mg or placebo for 6 months. Pre-stroke PA was measured using the Physical Activity Scale for the Elderly (PASE) and dichotomized by overall median value. Depressive symptoms were measured using the Major Depression Inventory (MDI) at one and six months after stroke. We used multivariable linear regression models to evaluate the interaction of pre-stroke PASE score and post-stroke MDI score. Results: We included 543 patients with complete PASE and MDI data at one month. Of these, 257 (47.3%) were in the SSRI group, 75% were men, and median (interquartile range) age was 69 (60 to 77). Overall, high PASE score was associated with lower MDI scores both one month (mean difference [confidence interval (CI)] -2.02 [-3.28 to -0.75]) and six months (-1.71 [-3.21 to -0.2]) after stroke. At one-month, a high PASE score was associated with lower MDI scores in the placebo group (mean difference -2.14 [-3.74 to -0.54]). After six months, an association between high pre-stroke PASE and lower MDI score was only found in the Citalopram group (mean difference -1.71 [-3.21 to -0.2]). Among patients with high pre-stroke PASE score the Citalopram group had lower MDI scores than the placebo group at six months (mean diff 2.01 [0.25 to 3.77]). Conclusions: High pre-stroke PA was independently associated with fewer depressive symptoms one and six months after stroke, however at six months the association was only present among those treated with Citalopram, suggesting an effect modification by Citalopram on the effect of PA on depressive symptoms. Further trials are warranted to verify these results.

Abstract 39: Ability Of Radiomics Versus Humans In Predicting First-pass Effect After Endovascular Treatment In The Escape-na1 Trial

Introduction: First-pass effect (FPE), i.e., achieving reperfusion with a single thrombectomy device pass, is associated with better clinical outcomes in patients with acute stroke. FPE is therefore increasingly being used as a marker of device and procedural efficacy. We evaluated the ability of thrombus-based radiomics models to predict FPE in patients undergoing endovascular thrombectomy (EVT) and compare performance to experts and non-radiomics thrombus characteristics. Methods: Patients with thin-slice non-contrast CT and CT angiography from The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial were included. Thrombi were manually segmented on all images. Data was randomly split into a derivation set that included a training and a validation subset and an independent test set. Radiomics features were extracted from the derivation data set. Three expert stroke physicians reviewed baseline imaging and clinical data for the test set. The machine learning (ML) models were compared to the three experts in predicting the primary outcome (FPE) in the test set using area under the receiver operating characteristic curves (AUC-ROC). Results: A total of 554 patients with available thin-slice images comprised of a derivation set (training subset [n=388, 70%]), validation subset [n=55, 10%]), and a test set (n=111, 20%). FPE was seen in 31.8% in the derivation set and 31.5 % in the test set. AUC of the best radiomics model was 0.74 (95% CI: 0.64, 0.84), which was higher than the mean AUC of the three experts 0.60 (95% CI: 0.50, 0.71) ( P =0.009). Specificity of radiomics was better than the mean specificity of the three experts, 46 of 76 (60%) vs. 35 of 76 (46.4%), P =0.004, whereas sensitivity was not significantly different between radiomics (28 of 35 [79%]) and experts (27 of 35 [77%]). Moreover, radiomics features performed better than non-radiomics features such as thrombus volume and permeability measurements in predicting FPE ( P &lt;0.05). Conclusion: A radiomics-based ML model of thrombus characteristics on non-contrast CT and CT angiography performs better than experts and non-radiomics image characteristics in predicting FPE in patients with acute stroke treated with EVT.

Abstract WMP87: Effect Of Intensive Blood Pressure Treatment After Successful Reperfusion On Outcome According To End Of Procedure Blood Pressure: Insight From The Bp Target Trial

Backgroup: The Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP TARGET) trial demonstrated no benefit of systolic blood pressure (SBP) intensive lowering treatment after successful reperfusion. However, it is still unknown whether end of procedure SBP modifies the treatment effect of SBP intensive lowering treatment after successful reperfusion. Methods: This is a post hoc analysis of the BP TARGET multicenter trial. Patients were enrolled in the BP TARGET trial if they achieved successful reperfusion with EVT and had systolic blood pressure (SBP) ≥130 mmHg at the end of procedure. Patients were randomized in 1:1 fashion to intensive SBP treatment (SBP target 100-129 mmHg to be achieved within 1 hour of randomization) or standard SBP treatment (SBP target 130-185 mmHg). In this study, patients were divided into two groups based on end of procedure SBP (&lt;160 mmHg, ≥ 160 mmHg). Primary outcome was any intracerebral hemorrhage and secondary outcome was favorable outcome ( modified Rankin Scale 0-2 ) at 90 days. Results: A total of 290 patients were included in the present study (141 patients in the intensive treatment arm and 149 patients in the standard arm). A total of 105 patients had end of procedure SBP≥160 mmHg (53 in the intensive arm and 52 in the standard arm) and 185 patients had SBP&lt;160mmHg (88 in the intensive arm and 97 in the standard arm). Intensive SBP treatment was not associated with any intracerebral hemorrhage or favorable outcome in both &lt;160 mmHg and ≥160mmHg groups (Table 1). Moreover, there was no heterogeneity of treatment effect according to end of procedure SBP. Conclusion: End of procedure SBP did not modify the treatment effect of SBP lowering treatment after successful reperfusion.

Abstract 6: A Comparison Of The Modified Rankin Scale And Stroke Impact Scale-ADL For Measuring Function After Stroke

Introduction: The modified Rankin Scale (mRS) of clinician-rated global disability is commonly used to measure functional outcome after stroke but has limitations such as low granularity and ceiling effects. Measures of functional outcomes with higher resolution could provide improved insights into outcomes and therapeutic efficacy. Here we evaluated the performance of the mRS in relation to the Stroke Impact Scale v2.0 Activities of Daily Living score (SIS-ADL), a valid, reliable, patient-reported measure of post-stroke function. Methods: Patients in the STRONG Study were examined 90 d post-stroke. In addition to the mRS, exam included the SIS-ADL, which asks patients to rate the difficulty of performing 10 ADLs using a 5-level Likert Scale. SIS-ADL scores range from 0-40; higher scores indicate better function. Results: For 499 patients, age = 61.5±14.8 (mean±SD), acute NIHSS = 4 [2-9] (median [IQR], day 90 mRS median = 2 [1-3], and day 90 SIS-ADL median = 35 [26-39]. The d90 SIS-ADL correlated with d90 mRS (r = -0.74, p&lt;.0001). The mean SIS-ADL value decreased with increasing mRS scores, as expected, but there was substantial overlap in SIS-ADL scores across mRS levels (Figure) to a degree beyond the minimal clinically important difference (5.9 points). The SIS-ADL was sensitive to mild deficits, identifying persistent ADL problems in 30/66 (45.5%) patients with a perfect mRS score of 0. Conclusions: In a population of mild-moderate stroke, the SIS-ADL identified a wide range of patient-reported functional deficits within each mRS level and was sensitive to functional deficits not identified by the mRS. The SIS-ADL complements the mRS for measuring functional outcome after stroke and may be useful for study design and sample size estimates for acute stroke and stroke recovery trials.

The Challenge of Designing Stroke Trials That Change Practice: MCID vs. Sample Size and Pragmatism.

Randomized controlled trials (RCT) are the basis for evidence-based acute stroke care. For an RCT to change practice, its results have to be statistically significant and clinically meaningful. While methods to assess statistical significance are standardized and widely agreed upon, there is no clear consensus on how to assess clinical significance. Researchers often refer to the minimal clinically important difference (MCID) when describing the smallest change in outcomes that is considered meaningful to patients and leads to a change in patient management. It is widely accepted that a treatment should only be adopted when its effect on outcome is equal to or larger than the MCID. There are however situations in which it is reasonable to decide against adopting a treatment, even when its beneficial effect matches or exceeds the MCID, for example when it is resource-intensive and associated with high costs. Furthermore, while the MCID represents an important concept in this regard, defining it for an individual trial is difficult as it is highly context specific. In the following, we use hypothetical stroke trial examples to review the challenges related to MCID, sample size and pragmatic considerations that researchers face in acute stroke trials, and propose a framework for designing meaningful stroke trials that have the potential to change clinical practice.