Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

Abstract

Abstract. Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875.

Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials

“… MRI-1 [ 9 ] MRI-2 [ 10 ] Amiri-Nikpour et al 2014 [ 11 ] Xue et al 2016 (individual patient data provided by authors for dropout inclusion) [ 12 ] …”

“…For the present meta-analysis, all sites were included capturing the aggregate data from the integrated clinical study report. For study Xue 2016 [ 12 ], raw data of dropouts were provided by the authors in order to allow LOCF analysis. Besides the sources listed above, no further data have been provided by authors of abstracts or unpublished but registered studies.…”

“…The rate of missing NIHSS values as compared to randomized subjects was below 10% in eight out of nine trials, thus well fulfilling the criteria for class I studies. For the five IPD studies [ 2 , 4 – 8 ] and for one study with aggregate data [ 12 ], replacement of missing values was performed by means of the LOCF technique (for Xue 2016, the authors provided requested raw data in order to allow LOCF imputation). In three studies, only observed cases (OC) data were available for NIHSS evaluation [ 9 – 11 ]; however, the missing rates were well comparable between Cerebrolysin and placebo (7/67 vs. 8/66).…”

L-3-n-Butylphthalide reduces ischemic stroke injury and increases M2 microglial polarization

“…L-3-n-Butylphthalide (NBP) is originally extracted from celery seeds, and was approved for the treatment of ischemic stroke by China Food and Drug Administration (CFDA) in 2002, and clinical studies have demonstrated its efficacy and safety (Xue et al 2016 ). Mechanisms contributing to its efficacy include increasing axonal growth, promoting neurogenesis and neuroplasticity, alleviating oxidative stress, mitigating neuronal injury and suppressing apoptosis of neuronal cells (Sun et al 2017 ; Yang et al 2015 ; Zhang et al 2016a ; Zhao et al 2014 ).…”

Refocusing Neuroprotection in Cerebral Reperfusion Era: New Challenges and Strategies

“…For instance, the DL-3-n-butylphthalide (NBP) may act by improving mitochondria function and energy metabolism ( 39 ), decreasing oxidative damage and apoptosis ( 40 ), reducing inflammatory responses ( 41 ), and enhancing regional blood flow and angiogenesis ( 42 ) to protect against ischemic brain damage and to result in reduction of infarct volume ( 39 , 43 ). Clinical trials have also shown that NBP can improve outcomes of patients with stroke ( 44 , 45 ). In addition to NBP, statins ( 46 , 47 ), citicoline ( 48 ), and stem cells ( 49 ) are also purported to have multiple mechanisms of action for acute ischemic stroke.…”