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Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial.
Ni, J, Chen, H, Chen, G, Ji, Y, Yi, F, Zhang, Z, Yang, Y, Wu, J, Cai, X, Shao, B, et al
BMC neurology. 2020;(1):282
Abstract
BACKGROUND Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke. METHODS Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram. RESULTS In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups. CONCLUSIONS The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported. TRIAL REGISTRATION Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827 . Retrospectively registered June 13, 2019.
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Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.
Kim, BJ, Kwon, SU, Park, JH, Kim, YJ, Hong, KS, Wong, LKS, Yu, S, Hwang, YH, Lee, JS, Lee, J, et al
Stroke. 2020;(3):931-937
Abstract
Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
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[Influence of acupuncture combined with rehabilitation therapy on limb motor function and serum cAMP and cGMP in patients with hemiplegia of cerebral ischemic stroke].
Jing, FQ, Qin, H, Liu, H, Wang, ZL
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2020;(6):581-5
Abstract
OBJECTIVE To evaluate the therapeutic effect of the combined treatment with balance acupuncture therapy and exercise re-learning rehabilitation therapy and the impact on serum cAMP and cGMP in the patients with hemiplegia of cerebral ischemic stroke. METHODS A total of 90 patients of hemiplegia of cerebral ischemic stroke were randomized into an observation group and a control group, 45 cases in each one. All of the patients in the two groups received health education, diet guidance, routine symptomatic treatment as well as exercise re-learning rehabilitation therapy. Additionally, in the observation group, balance acupuncture therapy was applied, in which, the acupoints on the yang aspect of the human body, on the governor vessel and bladder meridian were adopted in the morning and those on the yin aspect of the human body, on the conception vessel and kidney meridian were stimulated in the afternoon. In the control group, the regular acupuncture was given. In the two groups, both acupuncture and rehabilitation therapies were given 5 days a week, 2 week-treatment as one course and totally 2 courses were required. Separately, before and after treatment, the score of Fugl-Meyer assessment (FMA) and the score of Chinese stroke scale (CSS) were recorded, the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) detected in serum and the clinical therapeutic effect were evaluated in the two groups. RESULTS After treatment, FMA score was increased in the patients of either of the groups as compared with that before treatment (P<0.01) and CSS score decreased as compared with that before treatment (P<0.01). After treatment, FMA score in the observation group was higher than that in the control group (P<0.01) and CSS score was lower than the control group (P<0.01). After treatment, the level of serum cAMP of the patients in either of the groups was increased as compared with that before treatment (P<0.01) and that of cGMP decreased as compared with that before treatment (P<0.01). After treatment, the level of cAMP in the observation group was higher than that in the control group (P<0.01) and that of cGMP was lower than the control group (P<0.01). The total effective rate was 93.3% (42/45) in the observation group, better than 73.3% (33/45) in the control group (P<0.01). CONCLUSION The balance acupuncture therapy combined with exercise re-learning rehabilitation effectively improves the motor function of the affected limb, relieves injury and regulate the levels of serum cAMP and cGMP in the patients with hemiplegia of ischemic stroke.
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Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage.
Woo, PYM, Ho, JWK, Ko, NMW, Li, RPT, Jian, L, Chu, ACH, Kwan, MCL, Chan, Y, Wong, AKS, Wong, HT, et al
BMC neurology. 2020;(1):401
Abstract
ASBTRACT BACKGROUND There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. METHODS This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). RESULTS No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79-15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28-2.59). CONCLUSIONS Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. CLINICAL TRIAL REGISTRATION Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123 . Date of Registration: 8th February 2013.
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PCSK9 inhibition in patients with and without prior myocardial infarction or ischemic stroke: A pooled analysis of nine randomized-controlled studies of alirocumab.
Bruckert, E, Kereiakes, DJ, Koren, MJ, Louie, MJ, Letierce, A, Miller, K, Cannon, CP
Journal of clinical lipidology. 2019;(3):443-454
Abstract
BACKGROUND Patients with prior cardiovascular events are at very high risk of recurrent events and may benefit from low-density lipoprotein cholesterol (LDL-C) lowering beyond that achieved with maximally tolerated statins. OBJECTIVE To assess potential differences between the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor, alirocumab, in patients with vs without prior myocardial infarction (MI)/ischemic stroke. METHODS Data (n = 4880) were pooled from nine ODYSSEY phase 3 trials of alirocumab 75/150 mg or 150 mg every 2 weeks, mostly on background statins ± other lipid-lowering therapies. Analyses were performed according to statin status, alirocumab dose, and control (placebo or ezetimibe). RESULTS Baseline LDL-C, non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B levels were lower and lipoprotein(a) higher in patients with than without prior MI/ischemic stroke. LDL-C levels were reduced from baseline to week 24 in patients with (51.1%-62.9%) and without (43.6%-58.3%) prior MI/ischemic stroke, with no significant interaction between prior MI/ischemic stroke status and LDL-C-lowering efficacy of alirocumab vs controls. Alirocumab significantly reduced other lipid/lipoproteins (including lipoprotein[a]) similarly in patients with/without MI/ischemic stroke. Week 24 LDL-C goal attainment rates for subgroups with/without prior MI/ischemic stroke on background statins were 74.1%-84.8% and 63.7%-74.7%, respectively. The safety profile of alirocumab was generally similar regardless of prior MI/ischemic stroke status. CONCLUSIONS Alirocumab significantly reduced LDL-C and other atherogenic lipids/lipoproteins in patients with prior MI/ischemic stroke, and the majority of this very high cardiovascular risk population achieved LDL-C goals; efficacy and safety results were similar in patients without prior MI/ischemic stroke.
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Effects of Tai Chi on Cerebral Hemodynamics and Health-Related Outcomes in Older Community Adults at Risk of Ischemic Stroke: A Randomized Controlled Trial.
Zheng, G, Zheng, X, Li, J, Duan, T, Ling, K, Tao, J, Chen, L
Journal of aging and physical activity. 2019;(5):678–687
Abstract
This study investigated the effects of Tai Chi compared with no exercise control on the cerebral hemodynamic parameters and other health-related factors in community older adults at risk of ischemic stroke. A total of 170 eligible participants were randomly allocated to Tai Chi or control group. The cerebral hemodynamic parameters and physical fitness risk factors of cardiovascular disease were measured at baseline, 12 weeks, and 24 weeks. After the 12-week intervention, Tai Chi significantly improved the minimum of blood flow velocity (BFVmin); BFVmean; pulsatility index and resistance index of the right anterior cerebral artery; and BFVmax, BFVmin, and BFVmean parameters of the right middle cerebral artery. Tai Chi training also decreased triglyceride, fasting blood glucose, and homocysteine levels, and improved balance ability. Therefore, the supervised 12-week Tai Chi exercise had potential beneficial effects on cerebral hemodynamics, plasma risk factors, and balance ability in older community adults at risk of ischemic stroke.
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Rationale and design to assess the efficacy and safety of HT047 in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase II trial.
Heo, SH, Song, J, Kim, BJ, Kim, H, Chang, DI, ,
Medicine. 2019;(43):e17655
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Abstract
BACKGROUND Though several neuroprotective agents have been evaluated as potential treatments for acute ischemic stroke, none have demonstrated a definitive treatment efficacy, which remains elusive. HT047 is an herbal extract of Scutellaria baicalensis and Pueraria lobata, both of which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurologic status, particularly motor function, in acute ischemic stroke patients, and to determine the safety of HT047. METHODS A multicenter, double-blind, randomized, placebo-controlled, 3-arm parallel group, phase II trial will be conducted in patients who have had an acute ischemic stroke within the past 14 days. The participating patients must have a Fugl-Meyer assessment (FMA) motor score ≤55, with arm or leg weakness, and Korean version of the National Institutes of Health Stroke scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg 3 times a day), low-dose HT047 (500 mg 3 times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. Secondary endpoints are as follows: the change in FMA motor score at weeks 4 and 8 from baseline; the change in FMA motor score at weeks 4, 8, and 12 from baseline according to the timing of treatment initiation (either within 1 week, or 1-2 weeks), or according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc); the change in K-NIHSS and Korean versions of the modified Rankin scale (K-mRS) and the modified Barthel index at weeks 4 and 12 from baseline; and the proportion of subjects at week 12 with a K-NIHSS score of 0 to 2, or with K-mRS scores of 0, ≤1, and ≤2. DISCUSSION This study is a 1st-in-human trial of HT047 to explore the efficacy and safety in acute ischemic stroke patients. The results will provide the appropriate dosage and evidence of therapeutic benefit of HT047 for stroke recovery. TRIAL REGISTRATION ClinicalTrials.gov (NCT02828540) Registered July 11, 2016.
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Warfarin loading dose guided by pharmacogenetics is effective and safe in cardioembolic stroke patients - a randomized, prospective study.
Ruzickova, T, Sramek, M, Kaplan, V, Kumstyrova, S, Lacinova, Z, Jansky, P, Magerova, H, Sarbochova, I, Schwabova, JP, Matoska, V, et al
The pharmacogenomics journal. 2019;(5):446-454
Abstract
Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment. Secondary endpoints were time to the first international normalized ratio (INR) in therapeutic range (2.0-3.0) and occurrence of serious adverse events. Consenting cardioembolic stroke patients were genotyped for CYP2C9 (cytochrome P450 2C9 gene) and VKORC1 (vitamin K epoxide reductase complex, subunit 1 gene) polymorphisms and a maintenance warfarin dose was estimated. Patients were randomized into two groups. The loading dose group (LDG) patients received twice the estimated dose in the first 2 days of treatment. The maintenance dose group (MDG) patients received the estimated dose directly from day one. The TTR in the first 10 days was significantly higher in the LDG than in the MDG (50.5% vs. 38.3%, p = 0.003). The time to the first INR in this range was significantly shorter in the LDG (5.24 vs. 7.3 days). There were no significant differences in the INR above this range or serious adverse events. Warfarin loading dose guided by pharmacogenetics after recent cardioembolic stroke improved the efficacy of warfarin initiation without increasing the risk of adverse events.
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The Efficacy of a Comprehensive Reminder System to Improve Health Behaviors and Blood Pressure Control in Hypertensive Ischemic Stroke Patients: A Randomized Controlled Trial.
Wan, LH, Zhang, XP, You, LM, Ruan, HF, Chen, SX
The Journal of cardiovascular nursing. 2018;(6):509-517
Abstract
BACKGROUND AND OBJECTIVE The health behaviors of hypertensive stroke patients in China are not satisfactory. In this study, we tested the effect of a Health Belief Model Comprehensive Reminder System on health behaviors and blood pressure control in hypertensive ischemic stroke patients after occurrence and hospital discharge. METHODS A randomized, parallel-group, assessor-blinded experimental design yielded participation of 174 hospitalized hypertensive ischemic stroke patients. The intervention consisted of face-to-face and telephone health belief education, a patient calendar handbook, and weekly automated short-message services. Data were collected at baseline and 3 months after discharge. RESULTS Three months after discharge, the intervention group showed statistically, significantly better health behaviors for physical activity, nutrition, low-salt diet, and medication adherence. The intervention group also had statistically, significantly decreased systolic blood pressure and increased blood pressure control rate. Smoking and alcohol use behaviors were not affected. CONCLUSION At 3 months, use of the Comprehensive Reminder System based on the Health Belief Model, yielded improvement in most health behaviors and blood pressure control in hypertensive ischemic stroke patients. Continued implementation of this intervention protocol is warranted to determine the long-term effect. Smoking and alcohol use behaviors need to be targeted with a different intervention.
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A randomized controlled study of intravenous fluid in acute ischemic stroke.
Suwanwela, NC, Chutinet, A, Mayotarn, S, Thanapiyachaikul, R, Chaisinanunkul, N, Asawavichienjinda, T, Muengtaweepongsa, S, Nilanont, Y, Samajarn, J, Watcharasaksilp, K, et al
Clinical neurology and neurosurgery. 2017;:98-103
Abstract
OBJECTIVE To compare the outcome of patients with acute ischemic stroke who received or did not receive intravenous fluid. PATIENTS AND METHODS This study was a prospective, multicenter, randomized, open-label trial with blinded outcome assessment. We enrolled acute ischemic stroke patients without dehydration aged between 18 and 85 years with NIH Stroke Scale score (NIHSS) score from 1 to 18 who presented within 72h after onset. Patients were randomly assigned to receive 0.9% NaCl solution 100ml/h for 3days or no intravenous fluid. RESULTS On the interim unblinded analysis of the safety data, significant excess early neurological deterioration was observed among patients in the non-intravenous fluid group. Therefore, the study was prematurely discontinued after enrollment of 120 patients, mean age 60 years, 56.6% male. Early neurological deterioration (increased NIHSS ≥3 over 72h) not of metabolic or hemorrhagic origin was observed in 15% of the non-IV fluid group and 3.3% of the IV fluid group (p=0.02). Predictors of neurological deterioration were higher NIHSS score, higher plasma glucose, and increased pulse rate. There was no difference in the primary efficacy outcome, NIHSS≤4 at day 7, 83.3% vs 86.7%, p=0.61 or secondary efficacy outcomes. CONCLUSION Administration of 0.9% NaCl 100ml/h for 72h in patients with acute ischemic stroke is safe and may be associated with a reduced risk of neurological deterioration. These study findings support the use of intravenous fluid in acute ischemic stroke patients with NIHSS less than 18 who have no contraindications.