ObjectiveTo evaluate the current status and trend of methodological quality of multi-center randomized controlled trials (RCTs) of stroke treatments in Chinese Mainland.MethodsMulti-center RCTs of stroke treatments conducted in Chinese Mainland published in Chinese or English language from January 2000 to December 2019 were retrieved from seven databases including PubMed, Cochrane Central Registry of Controlled Trials, Embase, China Biology Medicine, China National Knowledge Infrastructure, Chinese Science and Technique Journals Database, and Wanfang Database. The basic information was collected. Methodological items were referred to the Cochrane Collaboration’s tool for assessing risk of bias. The definitions of Wade were used to assess the outcome measure.ResultsA total of 90 multi-center RCTs were included, of which 39 were published from 2000 to 2009, and 51 were published from 2010 to 2019. The total number of trials published from 2010 to 2019 was 1.31 times of that published from 2000 to 2009. The research subjects were ischemic stroke patients in 58.9% (53/90) of the RCTs, intracerebral hemorrhage patients in 14.4% (13/90) of the RCTs, and ischemic stroke patients as well as hemorrhagic stroke patients in 26.7% (24/90) of the RCTs. There were 55.6% (50/90) drug trials, and 44.4% (40/90) non-drug trials. There were statistically significant differences in the loss of visit report (P=0.005), primary and secondary outcome indicators report (P=0.027), and adverse reaction report (P=0.007) between the two periods; there was no statistically significant difference in reported adequate randomized methods (P=0.341), allocation concealment (P=0.611), blindness (P=0.551), used intentionality analysis (P=0.573), or follow-up time (P=0.061) between the two periods.ConclusionIn the past 20 years in Chinese Mainland, the quality of stroke treatment RCTs improves slowly, and more attention should be paid to develop the RCTs of true randomization, blinding, and better patient outcome measures.
Objectives To assess the efficacy and safety of dl-3-butylphthalide for patients with acute ischemic stroke. Methods We collected randomized controlled trials, which compared dl-3-butylphthalide agents with placebo or open control in patients with acute ischaemic stroke, by searching the electronic bibliographic databases, scanning references listed in articles and handsearching journals. Meta-analysis was conducted based on the methods recommended by the Cochrane Collaboration. Results Twenty-one trials involving 2 123 patients were included, of which 2 were placebo-controlled and 19 were open-label controlled. Meta-analysis of 10 trials (n=958), in which neurological deficits were assessed by CSS, suggested that there were significant differences favoring butylphthalide in the mean change of neurological deficits’ score during the treatment period [MD=2.30, 95%CI (1.57, 3.03)]. Meta-analysis of 6 trials (n=590), in which neurological deficits were assessed by NIHSS, also favored butylphthalide [MD=2.06, 95%CI (0.65, 3.46)]. Adverse events (AEs) were reported in 13 trials. Gastrointestinal discomfort (1.7%~8%) and abnormal liver function including abnormal ALT (1.4%~17.5%) and abnormal AST (1.9%~8.82%) were the two most common AEs. However, no severe adverse events (SAEs) were reported. Numbers of dead and dependent patients at the end of followup (at least three months) were not reported in the 21 included trials. Quality of life was not assessed in any of the trials. Conclusion Dl-3-butylphthalide can improve the neurological function after acute ischemic stroke and appears to be safe. However, further study is needed to confirm its effects for lowering rates of death and dependency.