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Research article
Peter Yat-Ming Woo
Kwong Wah Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7345-7904
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
There are limited treatment options for aneurysmal subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia, a major determinant of mortality and morbidity. Cerebrolysin, a brain-specific pleiotropic neuroprotective agent, has been suggested to improve functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of Cerebrolysin for conferring such benefits in SAH patients.
Methods
This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. 50 patients received either daily Cerebrolysin (30ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Score (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the occurrence of adverse effects, six-month mortality, the occurrence of cerebral vasospasm, delayed cerebral ischemia and infarction.
Results
No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 0.53; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for good six-month recovery indicated by a modified Rankin Scale of 0 to 2 (OR: 0.53; 95% CI 0.43-5.17) and a Barthel Index of 70 or more (OR: 0.52; 95% CI: 0.29-12.72) were also similar for both groups. There was a significantly lower risk of three- and six-month mortality for patients that received Cerebrolysin (OR: 0.46; 95% CI: 0.33-0.63). There were no deaths in the Cerebrolysin group, but the morality rate for the control group was 16% (4/25). The commonest cause of death was due to delayed cerebral ischemia. There were no differences in the overall incidence of delayed cerebral ischemia (p-value: 0.78), cerebral vasospasm (p-value: 0.16) and infarction (p-value: 0.77) between the two groups.
Conclusions
Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. Results suggest a benefit in reducing three- and six-month mortality. Due to the exploratory nature of this study and its small sample size, these findings should be confirmed in a larger-scale clinical trial.
Keywords
Aneurysmal subarachnoid hemorrhage, Neuroprotection, Neuroregeneration, Delayed ischemic neurological deficit, Vasospasm
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Peter Yat-Ming Woo
Kwong Wah Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7345-7904
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at BMC Neurology.
Version 1
Posted 16 Dec, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Neurology.
Background
There are limited treatment options for aneurysmal subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia, a major determinant of mortality and morbidity. Cerebrolysin, a brain-specific pleiotropic neuroprotective agent, has been suggested to improve functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of Cerebrolysin for conferring such benefits in SAH patients.
Methods
This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. 50 patients received either daily Cerebrolysin (30ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Score (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the occurrence of adverse effects, six-month mortality, the occurrence of cerebral vasospasm, delayed cerebral ischemia and infarction.
Results
No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 0.53; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for good six-month recovery indicated by a modified Rankin Scale of 0 to 2 (OR: 0.53; 95% CI 0.43-5.17) and a Barthel Index of 70 or more (OR: 0.52; 95% CI: 0.29-12.72) were also similar for both groups. There was a significantly lower risk of three- and six-month mortality for patients that received Cerebrolysin (OR: 0.46; 95% CI: 0.33-0.63). There were no deaths in the Cerebrolysin group, but the morality rate for the control group was 16% (4/25). The commonest cause of death was due to delayed cerebral ischemia. There were no differences in the overall incidence of delayed cerebral ischemia (p-value: 0.78), cerebral vasospasm (p-value: 0.16) and infarction (p-value: 0.77) between the two groups.
Conclusions
Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. Results suggest a benefit in reducing three- and six-month mortality. Due to the exploratory nature of this study and its small sample size, these findings should be confirmed in a larger-scale clinical trial.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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