Summary of findings 1. Cerebrolysin or Cerebrolysin‐like agents compared to placebo for acute ischaemic stroke.
| Cerebrolysin or Cerebrolysin‐like agents compared to placebo for acute ischaemic stroke | ||||||
| Patient or population: people with acute ischaemic stroke Settings: inpatient health facilities Intervention: Cerebrolysin or Cortexin added to standard therapy Comparison: placebo added to standard therapy | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Certainty of the evidence (GRADE) | ||
| Assumed risk | Corresponding risk | |||||
| Placebo | Cerebrolysin/Cortexin | |||||
| All‐cause death (follow‐up period up to 90 days) |
61 per 1000 47/767 (6.1%) |
58 per 1000 53/922 (5.7%) 3 fewer per 1000 (from 22 fewer to 22 more) |
RR 0.96 (0.65 to 1.41) | 1689 (6 RCTs) | ⊕⊕⊕⊝ Moderatea |
|
| Non‐death attrition |
145 per 1000 111/767 (14.5%) |
87 per 1000 80/922 (8.7%) 58 fewer per 1000 (from 39 fewer to 152 more) |
RR 0.72 (0.38 to 1.39) |
1689 (6 RCTs) | ⊕⊝⊝⊝ Very lowa,c | |
| Total number of people with SAEs** | Follow‐up period up to 90 days |
75 per 1000 50/668 (7.5%) |
87 per 1000 58/667 (8.7%) 12 more per 1000 (from 14 fewer to 47 more) |
RR 1.16 (0.81 to 1.66) |
1335 (3 RCTs) | ⊕⊕⊕⊝ Moderatea |
| Fatal, follow‐up period up to 90 days |
63 per 1000 42/668 (6.3%) |
57 per 1000 38/667 (5.7%) 6 fewer per 1000 (from 26 fewer to 24 more) |
RR 0.90 (0.59 to 1.38) | 1335 (3 RCTs) | ⊕⊕⊕⊝ Moderatea | |
| Non‐fatal, follow‐up period up to 90 days |
12 per 1000 8/668 (1.2%) |
30 per 1000 20/667 (3.0%) 18 more per 1 000 (from 0 fewer to 49 more) |
RR 2.39 (1.10 to 5.23) |
1335 (3 RCTs) | ⊕⊕⊕⊝ Moderatea | |
| Total number of people with adverse events, follow‐up period up to 90 days |
429 per 1000 314/732 (42.9%) |
387 per 1000
339/875 (38.7%) 42 fewer per 1000 (from 38 fewer to 55 more) |
RR 1.03 (0.92 to 1.14) | 1607 (4 RCTs) | ⊕⊕⊝⊝ Lowa,b | |
| Death or dependence, follow‐up period up to 90 days | Not reported | Not reported | ‐ | ‐ | ‐ | |
| Early death (within 2 weeks of stroke onset) | Not reported | Not reported | ‐ | ‐ | ‐ | |
| Quality of life | Not reported | Not reported | ‐ | ‐ | ‐ | |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial: RR: risk ratio; SAE: serious adverse event | ||||||
| GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate. | ||||||
**Results of the subgroup analysis:
Total number of people with SAEs, non‐fatal
A subgroup by Cerebrolysin dose and length of treatment (30 mL for 10 days), at the end of the follow‐up period: assumed risk 12 per 1000 7/600 (1.2%); corresponding risk 33 per 1000 20/589 (3.4%), 22 more per 1000 (from 3 more to 66 more)
RR 2.86 (1.23 to 6.66); number of participants (studies) 1189 (2 RCTs)
Certainty of the evidence ⊕⊕⊕⊝ Moderatea
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aWe downgraded by one level for risk of bias because most information came from studies at low or unclear risk of bias, with high levels of exclusion from the final analyses, retrospective registration, and other methodological flaws as described in Assessment of risk of bias in included studies. The manufacturer of Cerebrolysin supported CASTA 2012 and CERE‐LYSE‐1 2012 by providing services including: provision of Cerebrolysin and placebo, randomisation codes, and statisticians.
bWe downgraded by one level for inconsistency: heterogeneity with I2 = 37% for the overall effect estimate owing to the opposite direction of effect estimate in the Ladurner 2005 study (high cumulative dose of Cerebrolysin), and heterogeneity with I2 = 65% in the subgroup of two multicentre studies with the same dosing schedule (CASTA 2012; CERE‐LYSE‐1 2012).
cWe downgraded by one level for inconsistency and by one level for imprecision. Five trials contributed to the outcome non‐death attrition; we detected heterogeneity, with I2 = 57% for the overall effect estimate and I2 = 66% for subgroup differences, and heterogeneity with I2 = 47% in the subgroup of two multicentre studies with the same dosing schedule (CASTA 2012; CERE‐LYSE‐1 2012). The confidence intervals were wide.