Abstract P148: Safety And Efficacy Of Edaravone Dexborneol Versus Edaravone Alone For The Treatment Of Acute Ischemic Stroke Patients With Hypertention: Analysis From Taste Trial

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Jie Xu ◽  
Yongjun Wang

Background and Aims: Evidenced by TASTE phase III trial, 90-day good functional outcomes favored the edaravone dexborneol group versus edaravone group when administered within 48 hours after Acute Ischemic Stroke (AIS). The present study aimed to investigate the effects of edaravone dexborneol versus edaravone in AIS patients with hypertension medical history. Methods: This study was a subgroup analysis of the TASTE trial with hypertension medical history. The primary outcome was the proportion of patients with modified Rankin Scale (mRS) score ≤1 on day 90 after randomization. The secondary outcome was the mRS score on day 90. The safety endpoints were the incidences of adverse events, serious adverse events and deaths. Analyses were by intention to treat. Results: We included 767 AIS patients with hypertension (390 in edaravone dexborneol group, 377 in edaravone group) in this analysis. Among them, 252 (64.62%) in edaravone dexborneol group versus 199 (52.79%) in edaravone group reached mRS score ≤1 on D90, revealing significantly higher proportion of mRS score ≤1 on D90 in edaravone dexborneol group (OR 1.63 [95% CI, 1.22-2.18]; P<0.001). Significant differences occurred between two groups in mRS score on D90 ([OR 1.32 [95% CI, 1.02-1.72]; P=0.038). The safety outcomes indicated that the two groups were similar in incidences of adverse events (366 [93.85%] versus 352 [93.37%], p=0.787), serious adverse events (48 [12.31%] versus 34 [9.02%], p=0.1405) and number of deaths (6 [1.54%] versus 4 [1.06%], p=0.56). Conclusion: This analysis demonstrated that AIS patients with hypertension receiving edaravone dexborneol had better functional outcomes than those with edaravone, which provided evidences for the clinical application of edaravone dexborneol in AIS patients with hypertension. Keywords: Edaravone dexborneol, Acute ischemic stroke, Hypertension, mRS score

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. e1091-e1104 ◽  
Author(s):  
Mitchell S.V. Elkind ◽  
Roland Veltkamp ◽  
Joan Montaner ◽  
S. Claiborne Johnston ◽  
Aneesh B. Singhal ◽  
...  

ObjectiveWe evaluated the effect of 2 doses of natalizumab on functional outcomes in patients with acute ischemic stroke (AIS).MethodsIn this double-blind phase 2b trial, patients with AIS aged 18–80 years with NIH Stroke Scale scores of 5–23 from 53 US and European sites were randomized 1:1:1 to receive a single dose of 300 or 600 mg IV natalizumab or placebo, with randomization stratified by treatment window (≤9 or >9 to ≤24 hours from patient's last known normal state). The primary endpoint was a composite measure of excellent outcome (modified Rankin Scale score ≤1 and Barthel Index score ≥95) at day 90 assessed in all patients receiving a full dose. Sample size was estimated from a Bayesian model; p values were not used for hypothesis testing.ResultsAn excellent outcome was less likely with natalizumab than with placebo (natalizumab 300 or 600 mg odds ratio 0.60; 95% confidence interval 0.39–0.93). There was no effect modification by time to treatment or use of thrombolysis/thrombectomy. For natalizumab 300 mg, 600 mg, or placebo, there were no differences in incidence of adverse events (90.0%, 92.1%, and 92.3%, respectively), serious adverse events (25.6%, 32.6%, and 20.9%, respectively), or deaths (6.7%, 4.5%, and 5.5%, respectively).ConclusionsNatalizumab administered ≤24 hours after AIS did not improve patient outcomes.ClinicalTrials.gov identifierNCT02730455Classification of evidenceThis study provides Class I evidence that for patients with AIS, an excellent outcome was less likely in patients treated with natalizumab than with placebo.


Stroke ◽  
2021 ◽  
Author(s):  
Iris Lettow ◽  
Märit Jensen ◽  
Eckhard Schlemm ◽  
Florent Boutitie ◽  
Fanny Quandt ◽  
...  

Background and Purpose: During the first days and weeks after an acute ischemic stroke, patients are prone to complications that can influence further treatment, recovery, and functional outcome. In clinical trials, severe complications are recorded as serious adverse events (SAE). We analyzed the effect of SAE on functional outcome and predictors of SAE in the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke). Methods: We performed a post hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled clinical trial of magnetic resonance imaging-guided intravenous thrombolysis with alteplase in patients with acute ischemic stroke and unknown time of onset. Functional outcome was assessed by the modified Rankin Scale 90 days after the stroke. SAE were reported to a central safety desk and recorded and categorized by organ system using Medical Dictionary for Regulatory Activities terminology. We used logistic regression analysis to determine the effect of SAE on functional outcome and linear multiple regression analysis to identify baseline predictors of SAE. Results: Among 503 patients randomized, 199 SAE were reported for n=110 (22%) patients. Of those patients who did suffer a SAE, 20 (10%) had a fatal outcome. Patients suffering from at least one SAE had a lower odds of reaching a favorable outcome (modified Rankin Scale score of 0–1) at 90 days (adjusted odds ratio, 0.36 [95% CI, 0.21–0.61], P <0.001). Higher age ( P =0.04) and male sex ( P =0.01) were predictors for the occurrence of SAE. Conclusions: SAEs were observed in about one in 5 patients, were more frequent in elderly and male patients and were associated with worse functional outcome. These results may help to assess the risk of SAE in future stroke trials and create awareness for severe complications after stroke in clinical practice. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01525290 and https://eudract.ema.europa.eu ; Unique identifier: 2011-005906-32.


Author(s):  
Stefan Strilciuc ◽  
László Vécsei ◽  
Dana Boering ◽  
Aleš Pražnikar ◽  
Peter Riederer ◽  
...  

We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE (Excerpta Medica Database, 1947 to March 2021), MEDLINE (1946 to March 2021), CENTRAL (1948 to March 2021) and Cochrane Database of Systematic Reviews (1995 to March 2021). Data collection and analysis was conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p&amp;gt;0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderat reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.


2016 ◽  
Vol 5 (3-4) ◽  
pp. 174-178 ◽  
Author(s):  
Inger R. de Ridder ◽  
Puck S.S. Fransen ◽  
Debbie Beumer ◽  
Olvert A. Berkhemer ◽  
Lucie A. van den Berg ◽  
...  

Introduction: Stroke etiology and outcome after ischemic stroke differ between men and women. We examined if sex modifies the effect of intra-arterial treatment (IAT) in a randomized clinical trial of IAT for acute ischemic stroke in the Netherlands (MR CLEAN). Patients and Methods: The primary outcome was the score on the modified Rankin scale at 90 days. We tested for interaction between sex and treatment and estimated the treatment effect by sex with multiple ordinal logistic regression with adjustment for prognostic factors. Results: All 500 patients were included in the analysis; 292 (58.4%) were men. The treatment effect (adjusted common odds ratio) was 2.39 [95% confidence interval (CI) 1.55-3.68] in men and 0.99 (95% CI 0.60-1.66) in women (pinteraction = 0.016). In women, mortality was higher in the intervention group than in the control group (24 vs. 15%, p = 0.07). Serious adverse events occurred more often in women than in men undergoing intervention. There were no differences in neuro-imaging outcomes. Discussion and Conclusion: Contrary to other studies, we found a significant interaction between sex and treatment effect in the MR CLEAN trial. Pooled analyses of all published thrombectomy trials did not confirm this finding. In MR CLEAN, women seem to have a slightly more unfavorable profile, causing higher mortality and more serious adverse events, but insufficient to explain the absence of an overall effect. This suggests a play of chance and makes it clear that IAT should not be withheld in women.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1305-1306
Author(s):  
J. Samanta ◽  
G. Naidu ◽  
A. Chattopadhyay ◽  
A. Basnet ◽  
T. Narang ◽  
...  

Background:Both methotrexate and apremilast were found to be effective in controlling joint disease in psoriatic arthritis (PsA) patients [1-4]. However, there are no head-to-head trials comparing the efficacy of these two drugs in PsA.Objectives:Primary outcome measure was rate of major cDAPSA response (>85% change in cDAPSA score from baseline) at week 24 and secondary outcome measures were ACR 20 response, change in Psoriasis Area and Severity Index (PASI), Maastricht enthesitis score, Leeds dactylitis index, and health assessment questionnaire-disability index (HAQ-DI) and number of adverse events at week 24 between methotrexate and apremilast groups.Methods:Single blinded (physician), parallel group, randomized controlled trial was conducted at a single centre in India between October 2019 and December 2020. Adult PsA patients (age>18 years), fulfilling CASPAR criteria, not receiving methotrexate/apremilast in last 3 months and never receiving bDMARDs or, JAK inhibitors, having active articular disease (one or more swollen joint or, having one or more tender entheseal point) were recruited in this study.Results:A total of 31 patients were recruited (15 in apremilast arm and 16 in methotrexate arm) amongst whom 26 patients completed 24 weeks follow up (13 patients in apremilast arm and 13 patients in methotrexate arm). At baseline, median (IQR) swollen joints were 2 (1) in apremilast group and 2.5 (4) in methotrexate group. Median cDAPSA score at baseline was 23 (9) in apremilast group and 20 (21) in methotrexate group. Major cDAPSA response at week 24 was achieved in three (20%) subjects in apremilast arm and six (37.5%) subjects in methotrexate arm (p=0.433). Seven (46.67%) subjects in apremilast group and nine (56.25%) subjects in methotrexate group achieved ACR 20 response at 24-weeks (p=0.724). The change of PASI score from baseline was significant in apremilast group (2.0, p=0.003) and methotrexate group (0.35, p=0.003), but when compared between the two groups, there was no significant difference(p=0.378). Change in enthesitis score was not significant in both the groups (0.0 in apremilast group, p=0.285; 0.0 in methotrexate group, p=1.0). The median change in dactylitis score [0.0 (9.1), p=0.028] and HAQ-DI score (0.33, p=0.01) were significant in methotrexate group only. However, when compared to the change in apremilast group, the difference was not significant for both the parameters. A total of 9 minor adverse events, 3 with apremilast and 6 with methotrexate, were observed with transaminitis (number of events) being the commonest event noted with methotrexate. There were no serious adverse events noted in either of the groups.Conclusion:There was no significant difference between methotrexate and apremilast in terms of efficacy as measured by cDAPSA and ACR20 responses. Both the drugs were well tolerated by the study population. A larger study with head-to-head comparison between methotrexate and apremilast is needed to conform these findings.References:[1]Baranauskaite A, Raffayová H, Kungurov NV, et al; RESPOND investigators. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study Ann Rheum Dis. 2012;71:541-8.[2]Mease PJ, Gladman DD, Collier DH, et al. Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial. Arthritis Rheumatol 2019;71:1112-24.[3]Gladman DD, Kavanaugh A, Gómez-Reino JJ, et al. Therapeutic benefit of apremilast on enthesitis and dactylitis in patients with psoriatic arthritis: a pooled analysis of the PALACE 1-3 studies. RMD Open. 2018;4(1):e000669.[4]Wells AF, Edwards CJ, Kivitz AJ, et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. Rheumatology (Oxford) 2018;57:1253-63.Disclosure of Interests:None declared.


Stroke ◽  
2021 ◽  
Author(s):  
Jie Xu ◽  
Anxin Wang ◽  
Xia Meng ◽  
Gulbahram Yalkun ◽  
Anding Xu ◽  
...  

Background and Purpose: Edaravone dexborneol, comprised of 2 active ingredients, edaravone and (+)-borneol, has been developed as a novel neuroprotective agent with synergistic effects of antioxidant and anti-inflammatory in animal models. The present clinical trial aimed at testing the effects of edaravone dexborneol versus edaravone on 90-day functional outcome in patients with acute ischemic stroke (AIS). Methods: A multicenter, randomized, double-blind, comparative, phase III clinical trial was conducted at 48 hospitals in China between May 2015 and December 2016. Inclusion criteria included patients diagnosed as AIS, 35 to 80 years of age, National Institutes of Health Stroke Scale Score between 4 and 24, and within 48 hours of AIS onset. AIS patients were randomized in 1:1 ratio into 2 treatment arms: 14-day infusion of edaravone dexborneol or edaravone injection. The primary end point was the proportion of patients with modified Rankin Scale score ≤1 on day 90 after randomization. Results: One thousand one hundred sixty-five AIS patients were randomly allocated to the edaravone dexborneol group (n=585) or the edaravone group (n=580). The edaravone dexborneol group showed significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization, compared with the edaravone group (modified Rankin Scale score ≤1, 67.18% versus 58.97%; odds ratio, 1.42 [95% CI, 1.12–1.81]; P =0.004). The prespecified subgroup analyses indicated that a greater benefit was observed in female patients than their male counterparts (2.26, 1.49–3.43 versus 1.14, 0.85–1.52). Conclusions: When edaravone dexborneol versus edaravone was administered within 48 hours after AIS, 90-day good functional outcomes favored the edaravone dexborneol group, especially in female patients. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02430350.


2020 ◽  
Vol 38 (4) ◽  
pp. 311-321
Author(s):  
Jiaying Zhu ◽  
Mengmeng Ma ◽  
Jinghuan Fang ◽  
Jiajia Bao ◽  
Shuju Dong ◽  
...  

Background: Statin therapy has been shown to be effective in the prevention of ischemic stroke. In addition, recent studies have suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcomes in the event of stroke. It was speculated that prestroke statin use may enhance collateral circulation and result in favorable functional outcomes. Objective: The aim of the study was to investigate the association of prestroke statin use with leptomeningeal collaterals and to determine the association of prestroke statin use with stroke severity and functional outcome in acute ischemic stroke patients. Methods: We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 h in the neurology department of West China Hospital from May 2011 to April 2017. Computed tomographic angiography (CTA) imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; the National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission; the modified Rankin scale (mRS) was used to measure outcome at 90 days; and premorbid medications were recorded. Univariate and multivariate analyses were performed. Results: Overall, 239 patients met the inclusion criteria. Fifty-four patients used statins, and 185 did not use statins before stroke onset. Prestroke statin use was independently associated with good collateral circulation (rLMCS > 10) (odds ratio [OR], 4.786; 95% confidence interval [CI], 1.195–19.171; P = 0.027). Prestroke statin use was not independently associated with lower stroke severity (NIHSS score≤14) (OR, 1.955; 95% CI, 0.657–5.816; p = 0.228), but prestroke statin use was independently associated with favorable outcome (mRS score≤2) (OR, 3.868; 95% CI, 1.325–11.289; P = 0.013). Conclusions: Our findings suggest that prestroke statin use was associated with good leptomeningeal collaterals and clinical outcomes in acute ischemic stroke (AIS) patients presenting with occlusion of the middle cerebral artery. However, clinical studies should be conducted to verify this claim.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.


Author(s):  
Chase A Rathfoot ◽  
Camron Edressi ◽  
Carolyn B Sanders ◽  
Krista Knisely ◽  
Nicolas Poupore ◽  
...  

Introduction : Previous research into the administration of rTPA therapy in acute ischemic stroke patients has largely focused on the general population, however the comorbid clinical factors held by stroke patients are important factors in clinical decision making. One such comorbid condition is Atrial Fibrillation. The purpose of this study is to determine the clinical factors associated with the administration of rtPA in Acute Ischemic Stroke (AIS) patients specifically with a past medical history of Atrial Fibrillation (AFib). Methods : The data for this analysis was collected at a regional stroke center from January 2010 to June 2016 in Greenville, SC. It was then analyzed retrospectively using a multivariate logistic regression to identify factors significantly associated with the inclusion or exclusion receiving rtPA therapy in the AIS/AFib patient population. This inclusion or exclusion is presented as an Odds Ratio and all data was analyzed using IBM SPSS. Results : A total of 158 patients with Atrial Fibrillation who had Acute Ischemic Strokes were identified. For the 158 patients, the clinical factors associated with receiving rtPA therapy were a Previous TIA event (OR = 12.155, 95% CI, 1.125‐131.294, P < 0.040), the administration of Antihypertensive medication before admission (OR = 7.157, 95% CI, 1.071‐47.837, P < 0.042), the administration of Diabetic medication before admission (OR = 13.058, 95% CI, 2.004‐85.105, P < 0.007), and serum LDL level (OR = 1.023, 95% CI, 1.004‐1.042, P < 0.16). Factors associated with not receiving rtPA therapy included a past medical history of Depression (OR = 0.012, 95% CI, 0.000‐0.401, P < 0.013) or Obesity (OR = 0.131, 95% CI, 0.034‐0.507, P < 0.003), Direct Admission to the Neurology Floor (OR = 0.179, 95% CI, 0.050‐0.639, P < 0.008), serum Lipid level (OR = 0.544, 95% CI, 0.381‐0.984, P < 0.044), and Diastolic Blood Pressure (OR = 0.896, 95% CI, 0.848‐0.946, P < 0.001). Conclusions : The results of this study demonstrate that there are significant associations between several clinical risk factors, patient lab values, and hospital admission factors in the administration of rTPA therapy to AIS patients with a past medical history of Atrial Fibrillation. Further research is recommended to determine the extent and reasoning behind of these associations as well as their impact on the clinical course for AIS/AFib patients.


BMC Neurology ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
James A. G. Crispo ◽  
Dylan P. Thibault ◽  
Yannick Fortin ◽  
Daniel Krewski ◽  
Allison W. Willis

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