CEREHETIS Investigators
Neuroprotection with Cerebrolysin could mitigate reperfusion injury and hemorrhagic transformation (HT) in acute ischemic stroke (AIS).
This was a prospective, randomized, open-label, active control, multicenter, 1:2 parallel-group phase IIIb pilot study. Cerebrolysin (30 mL/day/14 days) was started concurrently with alteplase, 0.9 mg/kg in 117 patients, whereas 201 control patients were given alteplase alone. The patients were followed in 24 h (V1), on day 7 (V2), 14 (V3), and 90 (V4). The primary outcome was the rate of any and symptomatic HT at V1-3. The secondary endpoints were evaluation of safety (screening for adverse events at V1-V3) and functional outcome measured with the National Institutes of Health Stroke Scale (NIHSS) at V1-3, and modified Rankin scale (mRS) at V4. The favorable functional outcome was considered as a mRS score of ≤2. Odds ratio (OR) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated.
Any HT: OR, 0.417 (95% CI, 0.200-0.871; p = 0.020); NNT (benefit), 10.86 (95% CI, 5.50-420.68). Symptomatic HT: OR, 0.171 (95% CI, 0.040-0.726; p = 0.017); NNT (benefit), 15.65 (95% CI, 8.33-129.10). No serious adverse event attributed to Cerebrolysin occurred. The groups did not differ in NIHSS score at V1 and V2, but it decreased noticeably in the case arm at V3 (p = 0.032). The mRS score remained similar in both groups at V4.
The early add-on of Cerebrolysin to reperfusion therapy was safe, and decreased the HT rate and neurological deficit, but that was of no impact on functional outcome.
ISRCTN87656744