Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage

Abstract

Asbtract Background There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. Methods This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). 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): 1.49; 95% confidence interval (CI): 0.43–5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79–15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28–2.59). Conclusions Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. Clinical trial registration Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123. Date of Registration: 8th February 2013.

The neuroprotection of cerebrolysin after spontaneous intracerebral hemorrhage through regulates necroptosis via Akt/ GSK3β signaling pathway

“…In the aneurysmal subarachnoid hemorrhage clinical retrospectively study, CBL injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients 44 , while a recent randomized, placebocontrolled, double-blind, pilot trial demonstrated that daily CBL (30 mL/day) is safe, well-tolerated, and feasible for SAH patients, but it does not improve the six-month global functional performance of patients 45 . In the present study, we found that CBL can improve early brain injury by alleviating brain edema and neuron necroptosis after SAH.…”

Cerebrolysin alleviates early brain injury after traumatic brain injury by inhibiting neuroinflammation and apoptosis via TLR signaling pathway

“…An observational retrospective clinical study also confirmed that CBL may improve the level of consciousness in stroke patients in a minimally conscious state 44 . A recent randomized, placebo-controlled, double-blind trial demonstrated that daily CBL (30 mL/day) is safe, well-tolerated, and feasible for subarachnoid hemorrhage patients, but it does not improve the six-month global functional performance of patients 45 . In the present study, we found that CBL can improve brain injury by alleviating brain edema, neuroinflammation, and neuronal apoptosis after TBI in animals and decrease neuroinflammation in TBI patients.…”

Role of Cerebrolysin® in Rehabilitation in Ischemic Stroke: A Case Report

“…The clinical research on Cerebrolysin ® in the late subacute to chronic phases is still ongoing, with only 1 published retrospective study on the reduction of spasticity, and 1 in patients with minimally conscious state after stroke [ 16 , 17 ]. Additionally, sufficient safety data in several neurological conditions, such as subarachnoid hemorrhage, traumatic brain injury, and mild cognitive impairment and dementia, have been published [ 18 – 20 ].…”