PDF: CARS
(2016)Objective
CARS tested whether Cerebrolysin improves upper limb motor function and global recovery in ischemic stroke patients undergoing early rehabilitation.
Study Summary
• Cerebrolysin significantly improved ARAT score at day 90 (MW=0.71)
• Secondary endpoints (NIHSS, Barthel, mRS) also favored Cerebrolysin
• No increase in serious adverse events; zero deaths in Cerebrolysin group
• Secondary endpoints (NIHSS, Barthel, mRS) also favored Cerebrolysin
• No increase in serious adverse events; zero deaths in Cerebrolysin group
Intervention
30 mL/day IV Cerebrolysin or placebo for 21 days, starting 24–72h post-stroke, with standardized rehab.
Inclusion Criteria
Age 18–80, supratentorial ischemic stroke >4cm³, ARAT<50, prestroke mRS 0–1, good comprehension
Study Design
Arms: Cerebrolysin vs Placebo
Patients per Arm: 104 Cerebrolysin, 104 Placebo
Outcome
• ARAT improvement: +30.7 vs +15.9
• Global outcome MW=0.62 (p<0.0001)
• mRS 0–1 at 90d: 42.3% vs 14.9%
• Global outcome MW=0.62 (p<0.0001)
• mRS 0–1 at 90d: 42.3% vs 14.9%
Bottom Line
Cerebrolysin significantly improved upper limb motor function and global recovery compared to placebo in subacute ischemic stroke patients, with a favorable safety profile.
Major Points
- 208 patients randomized to Cerebrolysin 30 mL/day or placebo, starting 24–72h post-stroke for 21 days
- Primary outcome: ARAT score on day 90; Cerebrolysin group showed significantly higher improvement (MW=0.71, p<0.0001)
- Secondary outcomes also favored Cerebrolysin for NIHSS, Barthel Index, mRS, and quality of life (MW range: 0.56–0.73)
- Global outcome showed small-to-moderate superiority of Cerebrolysin (MW=0.62)
- No increase in serious adverse events; zero deaths in Cerebrolysin group vs 4 in placebo
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled, multicenter trial
- Randomization
- Yes
- Blinding
- Patients, caregivers, assessors, and sponsors were blinded; infusion bags were masked
- Sample Size
- 208
- Follow-up
- 90 days
- Countries
- Romania, Ukraine, Poland
Primary Outcome
Definition: Change in Action Research Arm Test (ARAT) score from baseline to day 90
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Mean change: 15.9 ± 16.8 | Mean change: 30.7 ± 19.9 | - (0.63–0.79) | <0.0001 |
Limitations & Criticisms
- Small phase II sample size limits generalizability
- No central review of outcomes
- Possible imbalance due to limited power
- Limited to Eastern Europe; generalizability needs further testing
Citation
Stroke. 2016;47:151–159. doi:10.1161/STROKEAHA.115.009416