Effects of simultaneous use of Cerebrolysin and alteplase on hemorrhagic transformation of brain infarction and functional outcome in stroke patients: CEREHETIS, a randomized, multicenter pilot trial

Abstract

The study aimed to assess effects of the simultaneous use of Cerebrolysin and intravenous thrombolysis (Alteplase) on hemorrhagic transformation (HT) and functional outcome as well as to analyze the treatment safety in acute stroke patients. It was a prospective, randomized, open-label, multicenter, parallel-group, active-controlled pilot study (Trial Registration Number: ISRCTN87656744, https://doi.org/10.1186/ISRCTN87656744, Trial registration date: 16/02/2021). The intervention group (n=126) was treated with Cerebrolysin infusion (30 mL) started simultaneously with Alteplase (0.9 mg/kg) via a separate IV line. The Cerebrolysin treatment continued for 14 consecutive days with the baseline therapy along. The control group (n=215) received only Alteplase and the baseline therapy. The primary endpoints were the rate of any and symptomatic hemorrhagic transformation (HT) from admission to day 14. Secondary endpoints were treatment safety and functional outcome measured with the National Institutes of Health stroke scale (NIHSS) in 24 h and on day 14, and with the modified Rankin scale (mRS) on day 90. Treatment with Cerebrolysin resulted in a significant reduction of the symptomatic HT rate with an odds ratio of 0.248 (95% CI: 0.072-0.851; p=0.019). No serious adverse events related to Cerebrolysin were observed. On day 14, the intervention group showed a significant reduction in the NIHSS score (p=0.045). However, no difference in the mRS score was observed on day 90, but there was a trend towards its improvement. The combination of Cerebrolysin and Alteplase was safe and significantly reduced the rate of symptomatic HT and improved early neurological deficit. However, no difference in functional outcome was found on day 90, but there was a trend towards favorable functional outcome.