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Neurological Sciences : Official... Oct 2023The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights... (Meta-Analysis)
Meta-Analysis Review
AIM
The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights regarding this field's future research.
METHODS
We conducted a comprehensive search of the Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials and observational studies up until September 2022. We evaluated the studies' quality using the Cochrane risk of bias tool and the National Institutes of Health tool.
RESULTS
We included 11 studies with 2845 ALS patients. We found that edaravone improved the survival rate at 18, 24, and 30 months (risk ratio (RR) = 1.03, 95% confidence interval (CI) [1.02 to 1.24], P = 0.02), (RR = 1.22, 95% CI [1.06 to 1.41], P = 0.007), and (RR = 1.17, 95% CI [1.01 to 1.34], P = 0.03), respectively. However, the administration of edaravone did not result in any significant difference in adverse effects or efficacy outcomes between the two groups, as indicated by a P value greater than 0.05.
CONCLUSION
Edaravone improves survival rates of ALS patients at 18, 24, and 30 months with no adverse effects. However, edaravone does not affect functional outcomes. In order to ensure the validity of our findings and assess the results in accordance with the disease stage, it is essential to carry out additional prospective, rigorous, and high-quality clinical trials. The current study offers preliminary indications regarding the effectiveness and safety of edaravone. However, further comprehensive research is required to establish the generalizability and sustainability of the findings.
Topics: United States; Humans; Edaravone; Amyotrophic Lateral Sclerosis; Prospective Studies; Quality of Life; Severity of Illness Index
PubMed: 37249667
DOI: 10.1007/s10072-023-06869-8 -
Clinical Drug Investigation Jan 2023The efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the clinical application of edaravone in the treatment of ALS.
METHODS
PubMed, Embase, Chinese Biomedical Literature Database (CBM), Cochrane Library and Web of Science were searched through 09 March 2022 for randomized controlled trials (RCTs) on the safety and efficacy of edaravone versus placebo during follow-up of patients with ALS. A summary of the outcome measures with GRADE was performed. This study was registered on PROSPERO (ID: CRD 42022319997).
RESULTS
Five RCTs with a total of 566 participants were included, and there was a significant difference (mean difference [MD] 1.33, 95% confidence interval [CI] 0.33-2.34; p = 0.009) in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the treatment and placebo groups. The edaravone group had an increased grip strength (MD 0.26, 95% CI 0.03-0.49; p = 0.03) and modified Norris Scale score (MD 2.81, 95% CI 1.18-4.43; p = 0.0007). However, there were no significant differences between groups for the change in forced vital capacity (FVC)% (MD 0.55, 95% CI - 3.15 to 4.24; p = 0.77), pinch strength (MD 0.05, 95% CI - 0.05 to 0.16; p = 0.33) or Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score (MD - 4.76, 95% CI - 9.56 to 0.03; p = 0.05). The incidence of adverse events (AEs) (risk ratio [RR] 0.09, 95% CI 0.93-1.05; p = 0.65), serious adverse events (SAEs) (RR 0.72, 95% CI 0.52-1.00; p = 0.05) and the number of deaths (risk difference [RD] 0.00, 95% CI - 0.02 to 0.03; p = 0.83) were not statistically different from the placebo group. The quality of evidence was low only for SAEs, and the remaining outcome measures were of moderate quality.
CONCLUSIONS
Compared with placebo, edaravone may provide potential clinical benefits in the treatment of ALS and may not increase the number of AEs and deaths. However, due to the low-quality evidence of the included studies and the small sample size, more high-quality and high-standard research evidence is needed to confirm these results.
PROTOCOL REGISTRATION
This study was registered on PROSPERO (ID: CRD 42022319997).
Topics: Humans; Edaravone; Amyotrophic Lateral Sclerosis; Surveys and Questionnaires
PubMed: 36462105
DOI: 10.1007/s40261-022-01229-4 -
Acta Neurologica Belgica Jun 2024The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.
METHODS
The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.
RESULTS
The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.
CONCLUSION
Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.
Topics: Edaravone; Humans; Amyotrophic Lateral Sclerosis; Free Radical Scavengers; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38347315
DOI: 10.1007/s13760-024-02476-2 -
Clinical Therapeutics Dec 2022The management of acute stroke is challenging. The aim of this meta-analysis was to determine the efficacy and tolerability of edaravone, with or without... (Meta-Analysis)
Meta-Analysis
PURPOSE
The management of acute stroke is challenging. The aim of this meta-analysis was to determine the efficacy and tolerability of edaravone, with or without thrombolytic therapy, in the treatment of patients with acute ischemic stroke.
METHODS
The PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) and cohort studies. Mean differences (MD), risk ratios (RR), 95% confidence interval (CI), and heterogeneity were calculated.
FINDINGS
Totals of nine RCTs and four cohort studies were included, for a total of 2102 patients. In patients with acute ischemic stroke, edaravone monotherapy was associated with significantly improved Barthel Index of functioning in activities for daily living (MD, 23.95; 95% CI, 18.48 to 29.41; P < 0.001) and neurologic deficit, (as measured using the National Institutes of Health Stroke Scale score) (MD = -3.49; 95% CI, -5.76 to 1.22; P = 0.003), on short-term follow-up. However, edaravone was not associated with an improved rate of death or disability (RR = 0.75; 95% CI, 0.45 to 1.23; P = 0.25) on long-term follow-up.When plus to thrombolytic therapy, edaravone was associated with significant improvements in recanalization rate (RR = 1.71; 95% CI, 1.05 to 2.77; P = 0.03) and neurologic deficit (MD = 3.97; 95% CI, 5.14 to 2.79; P < 0.001), without an increase in the prevalence of bleeding events (RR = 1.11; 95% CI, 0.76 to 1.62; P = 0.59). However, edaravone did not have a significant effect on death or disability (RR = 0.85; 95% CI, 0.69 to 1.04; P = 0.12).
IMPLICATIONS
Based on the findings from the present meta-analysis, edaravone was an effective and well-tolerated neuroprotective agent in these patients with ischemic stroke. With the use of edaravone, activities of daily living and neurologic deficits, along with recanalization rates, were improved on short-term follow-up, but the long-term effects still need confirmation in larger-scale clinical trials.
Topics: Humans; Edaravone; Stroke; Ischemic Stroke; Neuroprotective Agents; Hemorrhage
PubMed: 36473732
DOI: 10.1016/j.clinthera.2022.11.005 -
Clinical Neurology and Neurosurgery Aug 2022Ischemic stroke is a major cause of death and disability. Despite major advances in reperfusion therapies, most patients don´t benefit from these treatments as the time... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ischemic stroke is a major cause of death and disability. Despite major advances in reperfusion therapies, most patients don´t benefit from these treatments as the time window for such interventions is limited. Therefore, other treatment options are desirable. Edaravone has been demonstrated in previous studies to reduce neurologic deficits in stroke patients.
OBJECTIVE
To test the hypothesis that edaravone reduces functional dependence in ischemic stroke patients.
MATERIAL AND METHODS
Systematic review and meta-analysis of randomized controlled trials and observational studies comparing edaravone to placebo in adult patients with ischemic stroke. The efficacy outcomes of interest were good and excellent functional outcomes at 90 days, defined as modified Rankin Scale (mRS) scores of 0-2 and 0-1 respectively. The safety outcomes of interest were intracranial hemorrhage and mortality.
RESULTS
19 studies were included. Edaravone treatment was associated with improved chances of 90-day good (OR=1.31, 95% CI 1.06-1.67) and excellent (OR=1.26, 95% CI 1.04-1.54) functional outcomes. Mortality was also lower in edaravone treated patients (OR=0.50, 95% CI 0.45-0.56). There were no differences in terms of intracranial hemorrhage. Most studies were observational and performed in Asian populations, especially Japan. Heterogeneity was high for all outcomes but reduced when analysis was restricted to randomized trials.
CONCLUSION
Edaravone is a promising treatment for ischemic stroke patients, with a more favorable time window. However, more randomized studies including patient populations outside Asia are required to confirm this hypothesis.
Topics: Adult; Antipyrine; Brain Ischemia; Edaravone; Free Radical Scavengers; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Treatment Outcome
PubMed: 35753163
DOI: 10.1016/j.clineuro.2022.107299 -
International Journal of Stroke :... Jan 2014Edaravone has been used in patients with acute ischemic stroke in Japan for over 10 years but does not have marketing authorization in Europe or America. Either patients... (Review)
Review
Edaravone has been used in patients with acute ischemic stroke in Japan for over 10 years but does not have marketing authorization in Europe or America. Either patients in Europe and America are not receiving an effective treatment, or those in Asia are being given a treatment which is not effective. Finding out which of these is true will require further clinical trials, and a better understanding of its efficacy in animal models may help inform the design of those trials so that it might be tested under conditions where there is the greatest prospect of success. We systematically reviewed the efficacy of edaravone in animal models of focal ischemia and summarized data using weighted mean difference DerSimonian and Laird random-effects modeling. We used stratified meta-analysis and metaregression to assess the influence of study design and methodological quality. We identified 49 experiments describing outcome in 814 animals; 30 experiments (519 animals) reported functional and 35 experiments (503 animals) reported structural outcome. Edaravone improved functional and structural outcome by 30·3% (95% confidence interval 23·4-37·2%) and 25·5% (95% confidence interval, 21·1-29·9%), respectively. For functional outcome, there was an inverse relationship between study quality and effect size (P < 0·0017). Effect sizes were larger in studies where randomization or blinded assessment was not reported. There was no evidence of publication bias. Edaravone is a promising treatment for stroke. However, because of the methodological weakness in current animal studies, no sufficient preclinical evidence is available to optimize the study design of clinical trials. Higher quality animal studies are expected to inform further clinical study.
Topics: Animals; Antipyrine; Brain; Brain Ischemia; Disease Models, Animal; Edaravone; Free Radical Scavengers; Neuroprotective Agents; Recovery of Function
PubMed: 24148907
DOI: 10.1111/ijs.12163 -
The Cochrane Database of Systematic... Dec 2011Neuroprotection is a promising therapeutic strategy for the treatment of acute ischaemic stroke. Edaravone is a neuroprotective agent that has been widely used in China,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuroprotection is a promising therapeutic strategy for the treatment of acute ischaemic stroke. Edaravone is a neuroprotective agent that has been widely used in China, and several studies have suggested that it may be beneficial in acute ischaemic stroke.
OBJECTIVES
To assess the efficacy and safety of edaravone for acute ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (November 2010) and the Chinese Stroke Trials Register (November 2010). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to November 2010), EMBASE (1980 to November 2010), China National Knowledge Infrastructure (1979 to November 2010), Chinese Biomedical Database (1979 to November 2010), Chinese Evidence-Based Medicine Database (November 2010) and Chinese Science and Technology Journals Database (1980 to November 2010). In an attempt to identify further published, unpublished and ongoing trials we searched reference lists and clinical trials and research registers, and contacted a pharmaceutical company, researchers and study authors.
SELECTION CRITERIA
We included randomised controlled trials comparing edaravone with placebo or no intervention in patients with acute ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors selected trials for inclusion, assessed trial quality and independently extracted the data.
MAIN RESULTS
We included three trials, involving 496 participants, and defined four trials as waiting assessment. All three included trials were of edaravone plus another treatment compared with the other treatment alone. The dose of edaravone injections in the three trials was the same at 60 mg per day. The course of treatment in all three trials is 14 days. None of the included trials reported the pre-specified primary outcome of death or dependency defined using the modified Rankin scale during the follow-up period. The three trials evaluated the effect of edaravone at different times and using different methods. All three trials reported adverse events; there were no differences between the treatment group and the control group. Overall, edaravone appeared to increase the proportion of participants with marked neurological improvement compared with the control group, and the difference was significant (risk ratio (RR) 1.99, 95% confidence interval (CI) 1.60 to 2.49).
AUTHORS' CONCLUSIONS
The risk of bias in the included trials was moderate and the sample was small. Hence, although the data in this review show an effective treatment trend of edaravone for acute ischaemic stroke, further large, high-quality trials are required to confirm this trend.
Topics: Antipyrine; Brain Ischemia; Edaravone; Free Radical Scavengers; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic; Stroke
PubMed: 22161410
DOI: 10.1002/14651858.CD007230.pub2 -
The Cochrane Database of Systematic... Feb 2011Intracerebral haemorrhage (ICH) causes significant morbidity and mortality. Prognosis for ICH patients is poor. Edaravone may be safe and effective in reducing the risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intracerebral haemorrhage (ICH) causes significant morbidity and mortality. Prognosis for ICH patients is poor. Edaravone may be safe and effective in reducing the risk of early death and improving long-term functional outcomes in survivors.
OBJECTIVES
To assess the safety and efficacy of edaravone for acute ICH.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (March 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2 2010), the Chinese Stroke Trials Register (August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to March 2010) and 12 Chinese databases (August 2010). We also searched ongoing trials registers, reference lists, relevant conference proceedings and contacted companies manufacturing edaravone.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which edaravone was compared with placebo, or edaravone plus routine treatment was compared with routine treatment alone, in patients with acute ICH.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data, collected adverse events data and contacted trialists for missing information.
MAIN RESULTS
We included 10 RCTs involving 768 participants; quality was generally poor. For all trials, the control group was usual care/routine therapy (not placebo), treatment allocation and outcome evaluations were not blinded or not described, and the primary outcome (death or dependency at the end of long-term follow-up) was not reported. Only one trial reported deaths, indicating that edaravone treatment did not decrease the number of deaths significantly either during the scheduled treatment (RR 0.62, 95% CI 0.11 to 3.50) or at three month follow-up (RR 0.93, 95% CI 0.20 to 4.32). Four studies assessed activities of daily living (ADL) but ADL score was not improved significantly (MD 21.65, 95% CI -6.98 to 50.28) at the end of long-term follow-up. Combining data from all studies, edaravone treatment did increase the rate of improvement of neurological impairment (RR 1.48, 95% CI 1.29 to 1.69) until the end of the scheduled treatment, but it is not clear that this translates to any longer-term benefit of clinical importance. Reported adverse events with edaravone were mild and were common (9%), but there was no significant difference in adverse effect between the two groups (RR 2.09, 95% CI 0.71 to 6.19).
AUTHORS' CONCLUSIONS
All 10 studies were inconclusive in finding a beneficial or deleterious effect provided by edaravone for the treatment of ICH. Further high quality, large scale RCTs are required.
Topics: Antipyrine; Cerebral Hemorrhage; Edaravone; Free Radical Scavengers; Humans; Randomized Controlled Trials as Topic
PubMed: 21328300
DOI: 10.1002/14651858.CD007755.pub2 -
Neurological Sciences : Official... Feb 2019Based on the results of randomized, double-blind, placebo-controlled trials, the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Based on the results of randomized, double-blind, placebo-controlled trials, the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain controversial. We performed a meta-analysis to evaluate the efficacy and safety of edaravone in the treatment of this disease.
METHODS
We searched PubMed, the Cochrane Library, and Embase from the inception of electronic data to April 2018. We included randomized, double-blind, placebo-controlled trials reporting amyotrophic lateral sclerosis patients receiving 60-mg intravenous edaravone or intravenous saline placebo for 24 weeks. The primary efficacy evaluation was changed in Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to after the trial. Measure of safety was the frequency of investigated adverse events and serious adverse events. Data synthesis and analysis and evaluation of risk of bias were performed using RevMan 5.3 software. Heterogeneity among studies was evaluated with the I statistic.
RESULTS
A total of 367 patients were analyzed across three randomized controlled trials (183 patients receiving intravenous edaravone; 184 receiving placebo). A difference in ALSFRS-R score between groups at 24 weeks was found (mean difference [MD] = 1.63, 95% confidence interval [CI] 0.26-3.00, P = .02). No differences in the frequency of adverse events (odds ratio [OR] = 1.22, 95% CI 0.68-2.19, P = .50) or serious adverse events (OR = 0.71, 95% CI 0.43-1.19, P = .20) were found.
CONCLUSION
Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients, with no severe adverse effects. Additional reliable randomized controlled trials with larger sample sizes will further assess the efficacy and safety of edaravone in amyotrophic lateral sclerosis.
CLINICAL TRIAL REGISTRATION
The systematic review and meta-analysis was registered in the international prospective register of systematic reviews. (PROSPERO registration number: CRD42018096191; http://www.crd.york.ac.uk/PROSPERO .).
Topics: Amyotrophic Lateral Sclerosis; Edaravone; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic
PubMed: 30483992
DOI: 10.1007/s10072-018-3653-2 -
Die Pharmazie Feb 2021Early administration of edaravone for acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) has a potential neuroprotective effect. This study... (Meta-Analysis)
Meta-Analysis
Early administration of edaravone for acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) has a potential neuroprotective effect. This study aimed to estimate the safety and efficacy of edaravone for AIS patients receiving IVT. We searched PubMed, Embase, Cochrane Library and Chinese Databases (CNKI database, Weipu database, and Wanfang database) for randomized controlled trials (RCT) from the inception of the database to 20 July 2020. Efficacy outcome was reduced National Institutes of Health Stroke Scale (NIHSS) score before and after treatment. Safety outcomes were intracranial hemorrhage (ICH) and mortality. Review Manager 5.3 and Stata 14.0 was used to perform the meta-analysis. A total of 1877 AIS patients from 17 studies were included, 939 (50.03%) patients received edaravone combined with alteplase treatment. Compared with alteplase alone, combined treatment reduced the NIHSS score (MD=3.95,95% CI 2.92-4.99, I² = 92%) and ICH (OR=0.44,95% CI 0.29-0.66, I² =0%) during hospitalization. There was no significant association between combined treatment and mortality during follow-up (OR=0.43,95% CI 0.13-1.42, I² =0%). Conclusions: Edaravone combined with alteplase seems to be safe and effective for AIS patients' short term outcomes.
Topics: Administration, Intravenous; Combined Modality Therapy; Drug Combinations; Edaravone; Humans; Ischemic Stroke; Mortality; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33714288
DOI: 10.1691/ph.2021.0949