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This phase II, randomized, double blinded, multi-center study aims to explore whether intravenous edaravone dexborneol (ED) could improve clinical outcomes in patients with anterior circulation stroke with successful endovascular reperfusion (ClinicalTrials.gov: NCT04667637 ). Eligible patients were randomly (1:1) assigned into ED, which received intravenous ED (37.5 mg, 2/day, for 12 days) or control group, which received placebo. The primary endpoint was favorable functional outcome (a modified Rankin Scale [mRS] of 0–2 at 90 days). Two hundred patients were enrolled, including 97 in ED group and 103 in control group. The proportion of patients with 90-day mRS (0–2) was 58.7% (54/92) in ED group and 52.1% (49/94) in control group (unadjusted odds ratio 1.37, [95% CI 0.76-2.44], P  = 0.29). This work suggests that intravenous ED is safe, but do not statistically improve 90-day functional outcomes in patients with anterior circulation stroke with successful endovascular reperfusion. Endovascular thrombectomy (EVT) achieves high recanalization rates in acute stroke, but many patients still experience poor outcomes. Here, the authors show that intravenous edaravone dexborneol (ED) is safe and reduces early hemorrhage but does not significantly improve 90-day functional outcomes in stroke patients after EVT.

BackgroundEdaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and (+)-borneol, a food additive with an anti-inflammatory effect in animal ischaemic stroke models. This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke (AIS).MethodsIn this multicentre, randomised, double-blind, multiple-dose, active-controlled, phase II clinical trial, patients with AIS within 48 hours after stroke onset were randomly assigned (1:1:1:1) to low-dose (12.5 mg), medium-dose (37.5 mg) or high-dose (62.5 mg) Edaravone Dexborneol groups, and an active control group with edaravone (30 mg) by 30 min intravenous infusion every 12 hours, for 14 consecutive days. The primary efficacy outcome was the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days and National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 14 days after randomisation. The safety outcome included any adverse event during 90 days after treatment.ResultsOf 385 patients included in the efficacy analysis, 94 were randomised to low-dose group, 97 to medium-dose group, 98 to high-dose group and 96 to the control group. No significant difference was observed among the four groups on mRS score (mRS ≤1, p=0.4054) at 90 days or NIHSS score change at 14 days (p=0.6799). However, a numerically higher percentage of patients with mRSscore ≤1 at 90 days in the medium-dose (69.39%) and high-dose (65.63%) groups was observed than in the control group (60.64%). No significant difference in severe adverse events was found among the four groups (p=0.3815).ConclusionsCompared with edaravone alone, Edaravone Dexborneol was safe and well tolerated at all doses, although no significant improvement in functional outcomes was observed at 90days.Trial registration number NCT01929096.

BackgroundEdaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol (TASTE) trial demonstrated its superior efficacy over edaravone alone for acute ischaemic stroke (AIS) patients. However, its efficacy in individuals undergoing endovascular therapy (EVT) remains uncertain.AimTo clarify the rationale and design of the TASTE II (TASTE-2) trial.DesignThe TASTE-2 is a multicentre, double-blind, randomised, placebo-controlled trial designed to evaluate the efficacy and safety of edaravone dexborneol in patients with AIS and large-vessel occlusion in the anterior circulation. The eligible participants, presenting with a National Institute of Health Stroke Scale score between 6 and 25 (range 0–42, with larger values suggesting severe neurological dysfunction) and an Alberta Stroke Program Early Computed Tomography Score ranging from 6 to 10 (range 0–10, with smaller values suggesting larger infarction) within the initial 24 hours after symptom onset, will be randomly allocated to either the edaravone dexborneol group or the placebo group in equal proportions prior to thrombectomy. The treatment will be continuously administered for a duration of 10–14 days. A follow-up period of 90 days will be implemented for all participants.Study outcomesThe primary efficacy outcome is defined as achieving favourable functional independence, measured by a modified Rankin Scale of 0–2 at 90 days. The primary safety outcome focuses on the incidence of serious adverse events.DiscussionThe TASTE-2 trial will provide evidence to determine whether the administration of edaravone dexborneol in AIS patients undergoing EVT could yield significant improvements in neurological function.

Contrast‐induced nephropathy (CIN) is a serious complication that occurs subsequent to the administration of contrast media for therapeutic angiographic interventions. As of present, no effective therapy exists to prevent its occurrence. This single‐center double‐blind randomized controlled trial aimed to evaluate the effect of edaravone, an antioxidant, in a group of high‐risk patients undergoing coronary angiography. Ninety eligible patients with chronic kidney disease Stages 3–4 were randomly assigned to either the control group (n = 45) or the intervention group (n = 45). In the intervention group, one dosage of edaravone (60 mg) in 1 L of normal saline was infused via a peripheral vein 1 h prior to femoral artery‐directed coronary angiography. Patients in the control group received an equal amount of infusion in their last hour before angiography. Both groups received intravenous hydration with 0.9% sodium 1 mL/kg/h starting 12 h before and continuing for 24 h after angiography. The primary outcome measure was the onset of CIN, defined as a 25% increase in serum creatinine levels 120 h after administration of contrast media. The occurrence of CIN was observed in 5.5% (n = 5) of the studied population: 2.2% of patients in the intervention group (n = 1) and 8.9% of controls (n = 4). However, this difference was not statistically significant. Administration of a single dosage of edaravone 1 h prior to infusion of contrast media led to a reduction in the incidence of CIN. Further investigations, employing larger sample sizes, are warranted to gain a comprehensive understanding of its efficacy. CONSORT diagram. The eligibility assessment of enrolled participants in the study.

Edaravone is one of the treatment options for Amyotrophic Lateral Sclerosis, but its therapeutic efficacy is limited due to the incapacity to cross the blood–brain barrier, as well as its short life span and poor stability, which is ultimately caused by its tautomerism in physiological condions. This work presents an overview about the use of several nanoformulations based on polymeric, protein, lipidic, or hybrid structure as suitable and stable drug delivery systems for encapsulating edaravone. We also evaluated the functionalization of nanoparticles with pegylated chains using the polyethylene glycol or tocopherol polyethylene glycol succinate and the possibility of preparing polymeric nanoparticles at different pH (7.4, 9, and 11). Edaravone was sucessfully encapsulated in polymeric, lipid–polymer hybrid, and lipidic nanoparticles. The use of higher pH values in the synthesis of polymeric nanoparticles has led to a decrease in nanoparticle size and an increase in the percentage of encapsulation efficiency. However, the resulting nanoformulations are not stable. Only polymeric and hybrid nanoparticles showed good stability over 80 days of storage, mainly at 4 °C. Overall, the nanoformulations tested did not show cytotoxicity in the SH-SY5Y cell line except the nanostructured lipid carrier formulations that showed some cytotoxicity possibly due to lipidic peroxidation. In conclusion, this work shows that edaravone can be encapsulated in different nanocarriers that could act as an interesting alternative for the treatment of Amyotrophic Lateral Sclerosis.

Neuroprotective drugs as adjunctive therapy for adults with acute ischemic stroke (AIS) remains contentious. This study summarizes the latest evidence regarding the benefits of neuroprotective agents combined with intravenous recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis. This study conducted a structured search of PubMed, the Cochrane Library, EMBASE, Wanfang Data, and CNKI databases from their inception to March 2024. Grey literature was also searched. The outcomes included efficacy (National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score) and safety (rate of adverse reactions). A total of 70 randomized controlled trials were selected for this network meta-analysis (NMA), encompassing 4,140 patients with AIS treated using different neuroprotective agents plus RT-PA, while 4,012 patients with AIS were in control groups. The top three treatments for NIHSS scores at the 2-week follow-up were Edaravone Dexborneo with 0.9 mg/kg rt-PA, Edaravone with 0.9 mg/kg rt-PA, and HUK with 0.9 mg/kg rt-PA. HUK with 0.9 mg/kg rt-PA, Dl-3n-butylphthalide with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA were ranked the top three for BI scores at the 2-week follow-up. The top three treatments with the lowest adverse effect rates were 0.6 mg/kg rt-PA, HUK with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA due to their excellent safety profiles. Compared to rt-PA alone, the combination treatments of Edaravone+rt-PA, Edaravone Dexborneol+rt-PA, HUK+rt-PA, Dl-3n-butylphthalide+rt-PA, and Ganglioside GM1+rt-PA have shown superior efficacy. This NMA suggest that combination therapies of neuroprotective agents and rt-PA can offer better outcomes for patients with AIS. The results support the potential integration of these combination therapies into standard AIS treatment, aiming for improved patient outcomes and personalized therapeutic approaches.

AbstractObjectiveTo assess the efficacy and safety of edaravone dexborneol, a multitarget brain cytoprotectant composed of antioxidant and anti-inflammatory ingredients, in improving functional outcomes among patients with acute ischaemic stroke undergoing endovascular thrombectomy.DesignMulticentre, double blind, randomised, placebo controlled trial.Setting106 hospitals in China between March 2022 and May 2023.Participants1362 patients with clinically diagnosed acute ischaemic stroke within 24 hours of symptom onset, aged 18-80 years, with a National Institutes of Health Stroke Scale (NIHSS) score of 6-25 and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6-10, confirmed large vessel occlusion in the anterior circulation, and planned endovascular thrombectomy.InterventionsPatients were randomly allocated in a 1:1 ratio to receive edaravone dexborneol 37.5 mg (edaravone, 30 mg; (+)−dexborneol, 7.5 mg; 690 patients) or placebo (672 patients) before endovascular thrombectomy and continued the regimen twice daily for a consecutive period of 10-14 days.Main outcome measuresFunctional independence at 90 days, defined as a modified Rankin Scale score (range 0 (no symptoms) to 6 (death)) of 0-2, and serious adverse events.ResultsOne patient from each group was lost to follow-up at 90 days. Of the 1360 patients included in the intention-to-treat analysis, 379 (55.0%) of 689 patients in the edaravone dexborneol group and 333 (49.6%) of 671 patients in the placebo group achieved functional independence on day 90 (risk ratio 1.11, 95% confidence interval (CI) 1.00 to 1.23; P=0.05; risk difference 5.4%, 95% CI 0.1% to 10.7%). Patients with mismatch at admission (defined as NIHSS score ≥10 and ASPECTS ≥9 or NIHSS score ≥20 and ≥7) were more likely to achieve functional independence in the subgroup analysis (55.5% (178/321) versus 42.9% (134/312); risk ratio 1.29, 1.10 to 1.52; risk difference 13.0%, 5.6% to 20.3%; P for interaction=0.003). The rates of serious adverse events were similar in the two groups (27.2% (188/690) versus 25.7% (173/672); risk ratio 1.06, 0.89 to 1.26; risk difference 1.5%, −3.2% to 6.2%: P=0.53).ConclusionsAmong patients with acute ischaemic stroke within 24 hours of symptom onset who underwent endovascular thrombectomy, those treated with edaravone dexborneol, compared with placebo, were more likely to achieve functional independence at 90 days without increased safety concerns. This effect seemed to be primarily driven by the subgroup with mismatch present at admission, suggesting that dedicated trials in this population may be warranted.Trial registrationClinicalTrials.gov NCT05249920.

Background Edaravone has been widely used in amyotrophic lateral sclerosis (ALS) treatment, and a sublingual (SL) tablet has been developed to offer a more convenient alternative for injection. We present a cost-utility analysis to comprehensively evaluate the costs and health outcomes of oral and intravenous edaravone for the treatment of ALS in Chinese medical context. Methods Cost-utility analysis of SL tablets of edaravone versus intravenous edaravone at home was performed by constructing a 20-year Markov model of ALS stage 1–4 and death. The data were extracted from the literature with model assumptions. Typical sensitivity analysis and scenario analysis for administering SL tablets at home versus intravenous tablets at the hospital were performed. Results In the base case analysis, with SL tablets and intravenous injections both at home, the model estimated an additional cost of ¥12,670.04 and an additional 0.034 QALYs over 20 years (life time) of modeling analysis, and the ICER was ¥372,648.24 per QALY. However, in the scenario of intravenous administration at the hospital, SL tablet was demonstrated dominance to intravenous injection. Conclusions Using 3 times the GDP per capita of China in 2023 as the threshold, the SL tablet edaravone was not cost-effective in the context of home treatment for both formulationst, but was dominance to intravenous injection in hospital treatment. The results highlighted the importance of treatment context for health economic analysis.

Background Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient. Methods All participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1β) within 14 days after stroke onset. Results Eighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score < 2 compared to those who did not receive this treatment (70.7% versus 47.8%; P  = 0.031). Furthermore, individuals receiving edaravone dexborneol injection exhibited lower expression levels of interleukin (IL)-1β, IL-6, and IL-17, along with higher levels of IL-4 and IL-10 expression during the acute phase of ischemic stroke ( P  < 0.05). These trends were not observed for IL-2, IL-5, IL-8, IL-12p70, tumor necrosis factor-α, interferon-γ [IFN-γ], and IFN-α ( P  > 0.05). Conclusions Treatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels. Trial registration ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .

Schizophrenia is considered as a main one of the public health issues, and imposes numerous burdens on patients and society. We previously reported, the pathophysiology of schizophrenia is influenced by inflammation and mitochondrial dysfunction. Edaravone (EDV) as a potent antioxidant with neuroprotective traits, has been approved for the treatment of amyotrophic lateral sclerosis (ALS), effecting through neutralizing soluble/insoluble peroxyl radicals. However, the main disadvantages of EDV are its low stability in aqueous media, poor water solubility, and un-optimized bioavailability. To effectively address these obstacles, nanogel was utilized as the drug vehicle. The decoration of nanogel surface with glutathione (GSH) was carried out to elevate edaravone’s brain delivery. The probable improvement in drug delivery of edaravone loaded GSH-nanogel is the main hypothesis of this study. In order to mimic schizophrenia-like behaviors, we applied two month of post-weaning social isolation stress (PWSI) to rodent model. The choice of PWSI model was made due to the maturation and development of prefrontal cortex and hippocampus during adolescence. In addition to causing oxidative stress and upregulating genes linked to innate immunity in the prefrontal cortex (PFC), the data showed that PWSI triggered schizophrenia-like behaviors in rats. This study demonstrated that treatment with edaravone loaded GSH-nanogel decreased the impact of PWSI on behavioral dysfunctions and oxidative stress in the PFC of rats. Edaravone loaded GSH-nanogel (GSH-PMAA-EDV) down-regulated Toll-like receptor 4 ( Tlr-4 ) and AMP-activated protein kinase ( Ampk ) gene expression which are involved in inflammation and cellular energy homeostasis, respectively. Increase immunoreactivity feedback and Brain-derived neurotrophic factor ( Bdnf ) as direct impact in neurogenesis and neural cell plasticity was observed in EDV loaded GSH-nanogel treated groups. edaravone loaded GSH-nanogel (100 µg/kg) in comparison to free form of edaravone (5 mg/kg) revealed more beneficial effects, which might be useful for future clinical use especially for the treatment of schizophrenia.