-
PloS One 2014Many of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several commonly used drugs for AIS directly or indirectly.
METHODS
A systematic literature review was performed to identify randomized controlled trials (RCTs) published prior to April 2013 for AIS therapies. The primary outcome measures were the National Institutes of Health Stroke Scale (NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and meta-regression are performed; lastly, performed a mixed treatment comparison was performed through the Bayesian methods.
RESULTS
Outcome of efficacy of therapies for acute ischemic stroke are as followed: All of the therapies mentioned above yielded results a more effective result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18-4.61); Sodium ozagrel + edaravone (RR 9.60, 95%CI 7.04-13.06); Edaravone (RR 4.07, 95%CI 3.30-5.01); Edaravone + Kininogenase (RR 15.33, 95%CI 10.03-23.05). The significant difference in efficacy between edaravone monotherapy and Sodium ozagrel + edaravone was evident (RR 0.43, 95%CI 0.08-0.61) and was also significant between efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI 2.47-6.24). The differences between the risk and benefit were not significant when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological function: Placebo served a significant difference in treating the defects of neurological function compared with Sodium ozagrel (WMD = -3.11, 95%CI -4.43 to -1.79), Sodium ozagrel + edaravone (WMD = -6.25, 95%CI -7.96 to -4.54) and Edaravone + Kininogenase (WMD = -3.47, 95%CI -5.73 to -1.21).
CONCLUSIONS
It provides that the efficacy of edaravone monotherapy in treatment was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone + Kininogenase monotherapy in treatment was more effective than Sodium ozagrel. Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone + Kininogenase can improve the nerve dysfunction.
Topics: Aged; Antipyrine; Bayes Theorem; China; Coagulants; Drug Therapy, Combination; Edaravone; Fibrinolytic Agents; Free Radical Scavengers; Humans; Kallikreins; Methacrylates; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome
PubMed: 24551100
DOI: 10.1371/journal.pone.0088440 -
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