Table 1.
Characteristics of the included studies and outcome events
| Trials | Muresanu et al18 | Chang et al17 | Amiri-Nikpour et al16 | Lang et al15 | Heiss et al14 | Ladurner et al13 |
|---|---|---|---|---|---|---|
| 1. Information on the included trials | ||||||
| Regions | Romania, Ukraine, and Poland | Korea | Iran | Austria, Croatia, UK, Czech Republic, and Slovakia | People’s Republic of China, Hong Kong, South Korea, and Myanmar | Austria, Czech Republic, and Hungary |
| Follow-up | 3 months | 3 months | 3 months | 3 months | 3 months | 3 months |
| Male (%) | 67.3 vs 60.6 | 82.9 vs 72.7 | 54.5 vs 47.6 | 66.7 vs 62.7 | 59.6 vs 60.4 | 60.9 vs 55.3 |
| Age (SD) (years) | 64.9 (9.8) vs 63.0 (10.6) | 64.7 (10.1) vs 63.0 (10.6) | 60 (9.6) vs 60.1 (10) | 65.5 (11.3) vs 67.0 (10.6) | 65.0 (12.2) vs 65.5 (11.7) | 65 (1.17) vs 65 (1.32) |
| NIHSS | 9.1 (3.2) vs 9.2 (3.2) | 8.4 (5.8) vs 7.0 (4.9) | 14 (13, 15) vs 14 (12, 16) | 12.3 (5.39) vs 11.0 (5.44) | 9 (6–33) vs 9 (6–26) | – |
| Stroke location | – | Cortical:subcortical:cortical–subcortical: 7:6:21 vs 8:3:22 | Anterior circulation %: 63.6 vs 76.2 | – | – | Left hemisphere %: 52.6 vs 45.6 |
| 2. Eligibility criteria and study design | ||||||
| Inclusion criteria | Ischemic supratentorial stroke with a volume of >4 cm3, ARAT <50 and GKCS >2, and age between 18 and 80 years | First unilateral infarction within 7 days, moderate-to-severe motor function involvement, and age between 18 and 80 years | Ischemic stroke within 6–24 hours, NIHSS score 6–22, focal neurological injury, and age between 18 and 85 years | Acute ischemic hemispheric stroke with a measurable neurological deficit and age between 18 and 80 years | Acute hemispheric ischemic strokes, NIHSS score 6–22, prestroke mRS 0–1, and age between 18 and 85 years | First acute ischemic stroke, GCS >10 and CNS 4.5–8.0, and age 45–85 years |
| Exclusion criteria | Progressive or unstable stroke, prestroke disability, experienced a stroke within the previous 3 months, alcohol or drug abuse, and expected survival <1 year | Progressive or unstable stroke, preexisting neurological or psychiatric disease, alcohol or drug abuse, and expected survival <1 year | Unstable stroke, seizure, any conditions interfering with neurological examination, prestroke disability, hypertension (>220/120 mmHg), and hemorrhagic stroke | Intracranial hemorrhage, prior stroke within the last 3 months, hypertension (>185/110 mmHg), epilepsy, receiving oral anticoagulants, and prior stroke | Stroke in the brain stem or the cerebellum, hemorrhagic strokes, unstable stroke, preexisting systemic disease, and hypertension (>220/120 mmHg) | Hemorrhagic stroke, transient ischemic attacks, uncontrollable hypertension, severe concomitant diseases, and prior stroke |
| Study design | Cerebrolysin (30 mL/day IV for 21 days) vs placebo add-on to rehabilitation therapy, beginning within 24–72 hours after stroke onset | Cerebrolysin (30 mL/day IV for 21 days) vs placebo add-on to rehabilitation therapy, beginning within 7 days after stroke onset | Cerebrolysin (30 mL/day IV for 10 days) vs placebo add-on to aspirin 100 mg daily, beginning within 6 hours after arriving to the hospital | Cerebrolysin (30 mL/day IV for 10 days) vs placebo, beginning within 1 hour after thrombolytic therapy with rt-PA | Cerebrolysin (30 mL/day IV for 10 days) vs placebo add-on to aspirin 100 mg daily, within 12 hours after stroke onset | Cerebrolysin (50 mL/day IV for 21 days) vs placebo add-on to aspirin 250 mg daily, within 24 hours after stroke onset |
| 3. Outcomes assessments | ||||||
| Primary outcomes | ARAT score at Day 90 | Fugl–Meyer score at Day 90 | NIHSS score at Day 90 | mRS and NIHSS at Day 90 | BI, mRS, and NIHSS at Day 90 | CNS and BI at Day 90 |
| Secondary outcomes | Gait velocity test, nine-hole peg test, NIHSS, mRS, GKCS, line cancellation test, gap detection test, SF-36, and GDS at Days 21 and 90 | DTI, rsfMRI, and laboratory data (hematology, blood chemistry, urinalysis) at Day 90 | Mean flow velocity and pulsatility index of cerebral arteries | BI, GOS, laboratory data, and adverse events at Day 90 | Responder (mRS, BI, and NIHSS), SF-12, overall death rate, time to death, laboratory data, and adverse events at Day 90 | GCS, CGI, MMSE, SST, self-assessment scale, HAMD, laboratory data, and adverse events at Day 90 |
Abbreviations: ARAT, Action Research Arm Test; BI, Barthel Index; CGI, Clinical Global Impression; CNS, Canadian Neurological Scale; DTI, diffusion tensor imaging; GCS, Glasgow Coma Scale; GDS, Geriatric Depression Scale; GKCS, Goodglass and Kaplan Communication Scale; GOS, Glasgow Outcome Scale; HAMD, Hamilton Rating Scale for Depression; IV, intravenous; MMSE, Mini-Mental State Examination; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; rsfMRI, resting-state functional magnetic resonance imaging; rt-PA, recombinant tissue plasminogen activator; SD, standard deviation; SF-12, Short Form 12 items; SF-36, Short Form 36 items; SST, Syndrome Short Test.