Neuroprotection in Acute Ischaemic Stroke
Aim: This multicentre, double-blind, placebo-controlled trial was conducted to assess the efficacy and safety of an adjuvant administration of Cerebrolysin® (CERE) in patients suffering from acute ischaemic stroke. Methods: Patients with a first acute ischaemic stroke of the middle cerebral artery were randomised to IV therapy either with placebo (n=68) or with CERE 50ml/day (n=78), for 21 days. Both groups were treated also with acetylsalicylic acid 250mg/day PO and pentoxifylline 300mg/day IV. Treatment was initiated within 24h (mean 12.9±8.1h) after onset of first symptoms. Patients were investigated on treatment days 1, 3, 7, 21 and a follow-up investigation was carried out 3 months after start of treatment. Clinical outcome was recorded on the Canadian Neurological Scale (CNS), Barthel Index (BI) and Clinical Global Impressions (CGI). CERE is a peptide preparation with proven neuroprotective (calpain and caspase inhibitor) and neurotrophic action, produced by a standardised enzymatic breakdown of lipid-free brain proteins. Results: Patients in the CERE group showed a significant improvement in motor functions (CNS, section A1) at the end of therapy (t-test p<0.05) when compared to the placebo group. CERE patients treated within 6 hours after onset of stroke showed a significant improvement in the CGI in the acute treatment phase (t-test p<0.05; CERE n=16, placebo n=14). In the subgroup of patients with a right-sided stroke, CERE patients had a significantly better performance in the BI than placebo patients (Mantel-Haenszel test p<0.001). CERE and placebo were well tolerated and safe. Three patients died in the placebo group, and 2 patients in the CERE group. Conclusion: CERE seems to be an effective adjuvant treatment for acute ischaemic stroke. Motor functions were significantly better, and subgroup evaluation showed that early CERE treatment was related to improved clinical outcome. Adjuvant CERE demonstrated a fast onset of action and offered the possibility for an accelerated rehabilitation probably due to its neuroprotective effect. Large clinical trials are needed to confirm these results.