Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials.
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ABSTRACT:
SUBMITTER: Bornstein NM
PROVIDER: S-EPMC5884916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cerebrolysin was reported to be effective in the neurological improvement of patients with acute ischemic stroke (AIS) in experimental models, while data from clinical trials were inconsistent. We performed a meta-analysis to explore the efficacy and safety of cerebrolysin for AIS. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials, which intervened within 72 hours after the stroke onset. We investigated the efficacy and safety outcomes, respectively. Risk ratios and mean differences were pooled with fixed-effects model or random-effects model. Seven studies were identified, involving 1779 patients with AIS. The summary results failed to demonstrate significant superiority of cerebrolysin in the assessment of efficacy outcomes of mRS and BI. Similarly, administration of cerebrolysin had neutral effects on safety outcomes compared with placebo, including mortality and SAE. However, the number of included studies was small, especially in the analysis of efficacy outcomes, which might cause publication bias and inaccurate between-studies variance in the meta-analysis. Conclusively, although it seemed to be safe, routine use of cerebrolysin to improve the long-term rehabilitation after stroke could not be supported by available evidence.
| S-EPMC5474547 | biostudies-literature
Project description:We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.
| S-EPMC8708612 | biostudies-literature
Project description:This study conducts a rapid health technology assessment to systematically evaluate the effectiveness, safety, and cost-effectiveness of Cerebrolysin as an adjunctive therapy for acute ischemic stroke to provide evidence-based medicine for clinical decisions of Cerebrolysin. All systematic reviews/meta-analyses, pharmacoeconomic studies, and health technology assessment reports of Cerebrolysin for the treatment of acute ischemic stroke before August 17, 2023, were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Weipu, Sinomed database and the official website of health technology assessment. According to the inclusion and exclusion criteria, 2 researchers independently carried out screening, data extraction, and quality evaluation and descriptively analyzed the results of the included studies. A total of 14 pieces of literature were incorporated, comprising 8 systematic reviews/meta-analyses and 6 pharmacoeconomic studies. In terms of effectiveness, compared to control groups, the use of Cerebrolysin as a treatment for acute ischemic stroke demonstrates certain advantages, including enhancement in total efficacy rate, neurological function, upper limb motor dysfunction, and facilitation of the recovery of activities of daily living. Especially in patients with moderate to severe acute ischemic stroke, Cerebrolysin has demonstrated the ability to enhance neurological function recovery and ameliorate disabilities. Regarding safety, adverse reactions were mild or comparable to those in the control group. The primary findings of economic studies reveal that advocating for the use of Cerebrolysin offers certain cost-effectiveness advantages. Cerebrolysin contributes to improved clinical efficacy and evaluation indexes while demonstrating favorable safety and economic benefits.
| S-EPMC10977584 | biostudies-literature
Project description:The aim of this trial was to investigate whether stroke patients who receive Cerebrolysin show improved motor function in the upper extremities at day 90 compared with patients who receive a placebo.This study was a prospective, randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Patients were treated with Cerebrolysin (30 mL/d) or a placebo (saline) once daily for 21 days, beginning at 24 to 72 hours after stroke onset. The patients also participated in a standardized rehabilitation program for 21 days that was initiated within 72 hours after stroke onset. The primary end point was the Action Research Arm Test score on day 90.The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo (Mann-Whitney estimator, 0.71; 95% confidence interval, 0.63-0.79; P<0.0001). The multivariate effect size on global status, as assessed using 12 different outcome scales, indicated a small-to-medium superiority of Cerebrolysin (Mann-Whitney estimator, 0.62; 95% confidence interval, 0.58-0.65; P<0.0001). The rate of premature discontinuation was <5% (3.8%). Cerebrolysin was safe and well tolerated.Cerebrolysin had a beneficial effect on function and global outcome in early rehabilitation patients after stroke. Its safety was comparable with that of the placebo, suggesting a favorable benefit/risk ratio. Because this study was exploratory and had a relatively small sample size, the results should be confirmed in a large-scale, randomized clinical trial.URL: http://www.clinicaltrialsregister.eu. Unique identifier: 2007-000870-21.
| S-EPMC4689177 | biostudies-literature
Project description:IntroductionThe overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined.Materials and methodsA comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the "Cochrane Handbook for Systematic Reviews of Interventions 5.0.2" were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate.ResultsSix randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD) ?=?24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD ?=?3.53 [-1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD ?=?-3.101 [-5.33, -0.89]; serum calcium: SMD ?=?2.18 [-0.8, 5.16]; serum iPTH: SMD ?=?0.06 [-0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine.ConclusionsThis meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate.
| S-EPMC4180498 | biostudies-literature
Project description:A disruption of white matter connectivity is negatively associated with language (recovery) in patients with aphasia after stroke, and behavioral gains have been shown to coincide with white matter neuroplasticity. However, most brain-behavior studies have been carried out in the chronic phase after stroke, with limited generalizability to earlier phases. Furthermore, few studies have investigated neuroplasticity patterns during spontaneous recovery (i.e., not related to a specific treatment) in the first months after stroke, hindering the investigation of potential early compensatory mechanisms. Finally, the majority of previous research has focused on damaged left hemisphere pathways, while neglecting the potential protective value of their right hemisphere counterparts for language recovery. To address these outstanding issues, we present a longitudinal study of thirty-two patients with aphasia (21 males and 11 females, M = 69.47 years, SD = 10.60 years) who were followed up for a period of 1 year with test moments in the acute (1-2 weeks), subacute (3-6 months) and chronic phase (9-12 months) after stroke. Constrained Spherical Deconvolution-based tractography was performed in the acute and subacute phase to measure Fiber Bundle Capacity (FBC), a quantitative connectivity measure that is valid in crossing fiber regions, in the bilateral dorsal arcuate fasciculus (AF) and the bilateral ventral inferior fronto-occipital fasciculus (IFOF). First, concurrent analyses revealed positive associations between the left AF and phonology, and between the bilateral IFOF and semantics in the acute - but not subacute - phase, supporting the dual-stream language model. Second, neuroplasticity analyses revealed a decrease in connection density of the bilateral AF - but not the IFOF - from the acute to the subacute phase, possibly reflecting post stroke white matter degeneration in areas adjacent to the lesion. Third, predictive analyses revealed no contribution of acute FBC measures to the prediction of later language outcomes over and above the initial language scores, suggesting no added value ofthe diffusion measures for languageprediction. Our study provides new insights on (changes in) connectivity of damaged and undamaged language pathways in patients with aphasia in the first months after stroke, as well as if/how such measures are related to language outcomes at different stages of recovery. Individual results are discussed in the light of current frameworks of language processing and aphasia recovery.
| S-EPMC9723316 | biostudies-literature
Project description: Not available
| S-EPMC7387239 | biostudies-literature
Project description:BackgroundCerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries.ObjectivesTo assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke.Search methodsIn May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma).Selection criteriaRandomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke.Data collection and analysisTwo review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data.Main resultsWe identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events: two trials reported on this outcome, with 90% confidence cerebrolysin increased the risks of serious adverse events by at least one third compared to placebo: 62/589 in cerebrolysin group versus 46/600 in placebo group; RR 1.37 90% CI 1.01 to 1.86 (2 trials, 1189 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence).Authors' conclusionsThe findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence suggesting that serious adverse events may be more common with cerebrolysin use in acute ischaemic stroke.
| S-EPMC6463907 | biostudies-literature
Project description:BackgroundCerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries.ObjectivesTo assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke.Search methodsIn May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma).Selection criteriaRandomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke.Data collection and analysisTwo review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data.Main resultsWe identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events (SAEs): there was no significant difference in the total number of SAEs with cerebrolysin (RR 1.16, 95% CI 0.81 to 1.67). This comprised no difference in fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the number of people with non-fatal SAEs (20/667 with cerebrolysin and 8/668 with placebo: RR 2.47, 95% CI 1.09 to 5.58, P = 0.03) (3 trials, 1335 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence).Authors' conclusionsThe findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total SAEs.
| S-EPMC6478305 | biostudies-literature
Project description: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.
| S-EPMC4840538 | biostudies-literature