scholarly journals Natalizumab in acute ischemic stroke (ACTION II)

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. e1091-e1104 ◽  
Author(s):  
Mitchell S.V. Elkind ◽  
Roland Veltkamp ◽  
Joan Montaner ◽  
S. Claiborne Johnston ◽  
Aneesh B. Singhal ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Acute Ischemic Stroke ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Excellent Outcome ◽  
Scale Scores ◽  
To Receive ◽  
Improve Patient

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.

Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms

2019 ◽  
pp. 331-340
Author(s):  
Susan Churchill ◽  
◽  
Kayla Deru ◽  
Lindell K. Weaver ◽  
Steffanie H. Wilson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Hyperbaric Oxygen ◽  
Gas Flow ◽  
Randomized Trials ◽  
Symptom Improvement ◽  
Sham Control ◽  
Serious Adverse Events ◽  
Double Blind ◽  
To Receive

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute, >99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.

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
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Acute Ischemic Stroke ◽  
Medical History ◽  
Functional Outcomes ◽  
Group Versus ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Serious Adverse Events ◽  
Intention To Treat

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

scholarly journals Fostamatinib for the treatment of hospitalized adults with COVD-19 A randomized trial

2021 ◽  
Author(s):  
Jeffrey R Strich ◽  
Xin Tian ◽  
Mohamed Samour ◽  
Christopher S King ◽  
Oksana Shlobin ◽  
...  
Keyword(s):  
Immune Response ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Reactive Protein ◽  
To Receive ◽  
Confirmatory Trials

Abstract Background Coronavirus Disease 2019 (Covid-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response and immunothrombosis. Fostamatinib, is a novel spleen tyrosine kinase inhibitor we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. Methods We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with Covid-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. Results A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared to 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs. -2.6 ± 0.4, P = .035) and the median length in the ICU was 3 days in the fostamatinib group vs. 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs. 28, P = .027). There were trends towards more rapid reductions in C-reactive protein, D-dimer, fibrinogen and ferritin levels in the fostamatinib group. Conclusion For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared to placebo. These results warrant further validation in larger confirmatory trials.

Serious Adverse Events and Their Impact on Functional Outcome in Acute Ischemic Stroke in the WAKE-UP Trial

Stroke ◽  
2021 ◽  
Author(s):  
Iris Lettow ◽  
Märit Jensen ◽  
Eckhard Schlemm ◽  
Florent Boutitie ◽  
Fanny Quandt ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Ischemic Stroke ◽  
Adverse Events ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Fatal Outcome ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Serious Adverse Events ◽  
Link Type

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.

scholarly journals Comparison of the Effect of Fimasartan versus Valsartan on Blood Pressure Variability in Acute Ischemic Stroke: A Double-Blind Randomized Trial

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Dong Hoon Shin ◽  
Soohwa Song ◽  
Yeong Bae Lee
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Pressure Variability ◽  
Controlled Trial ◽  
Poor Functional Outcome ◽  
Double Blind ◽  
Before And After ◽  
Average Real Variability ◽  
To Receive

Higher blood pressure variability (BPV) is associated with poor functional outcome and mortality in acute stroke. This randomized controlled trial was conducted to compare the effect on BPV between fimasartan and valsartan (Boryung Pharmaceutical Co., Ltd., Seoul, Republic of Korea) in patients with acute ischemic stroke. Eighty patients were randomly assigned to receive either valsartan or fimasartan after 7 days of acute ischemic stroke onset, for duration of 8 weeks. Of them, 62 patients completed the study [valsartan (n=31), fimasartan (n=31)]. We measured BP for 24 hours using ambulatory BP monitoring device before and after 8 weeks of starting BP medication. We calculated several indexes such as standard deviation (SD), weighted 24-hour BP with SD (wSD), coefficient of variation (CV), and average real variability (ARV) to assess BPV and to compare indexes of BPV between 2 drugs. SD values of systolic BP in daytime, nighttime, and 24 h period (15.55±4.02 versus 20.55±8.77, P=0.006; 11.98±5.52 versus 16.47±6.94, P=0.007; 17.22±5.30 versus 21.45±8.51, P=0.024), wSD of systolic BP (8.27±3.01 versus 10.77±4.18, P=0.010), and ARV of systolic BP (15.85±6.17 versus 19.68±7.83, P=0.040) of patients receiving fimasartan after 8 weeks were significantly lower than patients receiving valsartan. In paired t-test, SD values of daytime, nighttime, and 24 h period of systolic BP of patients receiving fimasartan were significantly decreased after 8 weeks (15.55±4.02 versus 18.70±7.04, P=0.038; 11.98±5.52 versus 17.19±7.35, P=0.006; 17.22±5.30 versus 20.59±5.91, P=0.015). Our study showed that fimasartan had greater effect on reducing BPV after acute ischemic stroke than valsartan. Trials registry number is KCT0003254.

scholarly journals Cardiac Tamponade after Thrombolysis for Acute Ischemic Stroke - A Case with an Excellent Outcome

2020 ◽  
Author(s):  
Ana Vera-Cruz ◽  
Marta Cerol ◽  
Maria Margarida Pereira ◽  
Sónia Canadas ◽  
Juliana Mortágua ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cardiac Tamponade ◽  
Intravenous Thrombolysis ◽  
Major Complication ◽  
Recombinant Tissue Plasminogen Activator ◽  
Serious Adverse Events ◽  
Excellent Outcome ◽  
Cardiac Symptoms ◽  
History Of

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the established treatment for acute ischemic stroke and has been highly effective in reducing the neurological deficit. Serious adverse events are not uncommon, with hemorrhage being the major complication. We describe the case of a patient with acute ischemic stroke that also presented with vague cardiac symptoms and was treated with rtPA, which was complicated by a hemopericardium causing cardiac tamponade. Pericardiocentesis was promptly performed, which resulted in rapid resolution of the cardiogenic shock. The patient recovered consciousness within a few minutes. A search of the MEDLINE database shows that this is the first report of cardiac tamponade after rtPA thrombolysis occurring in a patient with no history of recent myocardial infarction or aortic dissection.

scholarly journals Safety of Cerebrolysin for Neurorecovery After Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Twelve Randomized-Controlled Trials

2021 ◽  
Author(s):  
Stefan Strilciuc ◽  
László Vécsei ◽  
Dana Boering ◽  
Aleš Pražnikar ◽  
Peter Riederer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Acute Ischemic Stroke ◽  
Systematic Reviews ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Safety Information ◽  
High Dose ◽  
Serious Adverse Events

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.

scholarly journals Is Intra-Arterial Treatment for Acute Ischemic Stroke Less Effective in Women than in Men

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 ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Acute Ischemic Stroke ◽  
Treatment Effect ◽  
Primary Outcome ◽  
Intervention Group ◽  
Control Group ◽  
Serious Adverse Events ◽  
Neuro Imaging ◽  
Mr Clean

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.

Intracranial bailout stenting with the Acclino (Flex) Stent/NeuroSpeed Balloon Catheter after failed thrombectomy in acute ischemic stroke: a multicenter experience

2019 ◽  
Vol 12 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Christian Paul Stracke ◽  
Lukas Meyer ◽  
Jens Fiehler ◽  
Hannes Leischner ◽  
Maxim Bester ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Balloon Catheter ◽  
Safety Evaluation ◽  
Anterior Circulation ◽  
Serious Adverse Events ◽  
Atherosclerotic Stenosis ◽  
Scale Scores ◽  
Study Population

Background and purposeTo report on the feasibility, safety, and outcome of acute intracranial stenting (ICS) with the Acclino (Flex) Stent and NeuroSpeed Balloon Catheter in cases of failed mechanical thrombectomy (MT) for acute ischemic stroke (AIS).MethodsWe retrospectively reviewed the data of patients treated with acute bailout stenting after failed MT in three large neurointerventional centers using exclusively the Acclino (Flex) Stent and the NeuroSpeed Balloon Catheter. Functional outcome was assessed by the rate of major early neurological recovery (mENR) at 24 hours and at 90 days with the modified Rankin Scale (mRS). Safety evaluation included symptomatic intracranial hemorrhage (sICH), mortality, and intervention-related serious adverse events (SAEs).Results50 patients with a median age of 71 years met the inclusion criteria and 52% (26/50) of the occluded vessels were located within the anterior circulation. mENR was observed in 38.8% and 90-day favorable outcome (mRS ≤2) was 40.6% (13/32). Higher NIH Stroke Scale scores on admission were significantly associated with poor functional outcome (mRS ≥3) at 90 days (adjusted OR 1.28; 95% CI 1.07 to 1.53; p=0.007). sICH occurred in two cases of the study population. There were no intervention-related SAEs.ConclusionIntracranial bailout stenting with the Acclino (Flex) Stent and the NeuroSpeed Balloon Catheter after failed MT is a feasible and effective recanalization method for atherosclerotic stenosis-based stroke that is associated especially with low rates of sICH.

scholarly journals Treatment evaluation of acute stroke for using in regenerative cell elements (TREASURE) trial: Rationale and design

2017 ◽  
Vol 13 (4) ◽  
pp. 444-448 ◽  
Author(s):  
Toshiya Osanai ◽  
Kiyohiro Houkin ◽  
Shinichiro Uchiyama ◽  
Kazuo Minematsu ◽  
Akihiko Taguchi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Sample Size ◽  
Time Window ◽  
Therapeutic Window ◽  
Phase 2 ◽  
Double Blind ◽  
Significance Level ◽  
Double Blind Placebo ◽  
Excellent Outcome

Rationale MultiStem® (HLM051) is one of the promising allogenic cell products for acute ischemic stroke with strong evidence. A previous phase 2 randomized, double-blind, placebo-controlled, multicenter dose-escalation trial showed the safety of MultiStem® for acute ischemic stroke, with a time window beyond that of rt-PA and endovascular thrombectomy. We aim to obtain stronger evidence and to show the efficacy of the MultiStem® for treatment of ischemic stroke. Sample size Estimated sample size is 220 (110 patients per group), which has 90% power at 5% significance level. Methods and design TREASURE is a randomized, double-blind, placebo-controlled, multicenter phase 2/3 trial. The trial will be done at 31 medical centers in Japan. Patients with acute ischemic stroke including motor or speech deficit defined by a National Institution of Health Stroke Scale (NIHSS) score of 8–20 at baseline will be randomized 1:1 to receive a single intravenous infusion of MultiStem® or placebo within 18–36 h of stroke onset. Study outcomes Primary outcome in this study is the proportion of patients with an excellent outcome at day 90 defined by the functional assessment. Trial registration ClinicalTrials.gov (NCT02961504). Conclusion The TREASURE trial will provide a novel treatment option and expand the therapeutic window for patients with stroke if the results are positive.

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