Table 2.
Randomized controlled trials targeting immune cells in human ischemic stroke.
| Treatment | Mechanism | Author | Year | Study place | Sample Size | Intervention | Outcome | Reference | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Time window, duration | Drug dose | Administration route | mRS/ΔSSS/mBI at day 90 | Mortality rate | Infarct volume at day 5/NIHSS score at 1 week | Adverse event | |||||||
| Anti-ICAM-1 (Enlimomab) | Inhibiting leukocytes infiltration | Enlimomab Acute Stroke Trial Investigators | 2001 | USA Europe | Enlimomab (n=317) placebo (n=308) | Within 6 hours after onset; 5 days | LB: 160mg; MB: 40mg | Intravenously | worse | Higher | -* | More infections and fever | (214) |
| Anti-Mac-1(UK-279,276) | Inhibiting leukocytes infiltration | Krams | 2003 | UK | 966 patients randomly treated | Once within 6 hours after onset | 1 of 15 doses (dose range, 10 to 120 mg) | Intravenously | Not significant | Similar | – | More headache | (215) |
| Anti-α4 integrin (natalizumab) | Inhibiting lymphocyte infiltration | Elkins | 2017 | USA Europe | Natalizumab (n=79) Placebo (n=82) | Once up to 9 h after onset | 300 mg | Intravenously | More good outcome | – | Similar | Similar | (225) |
| Anti-α4 integrin (natalizumab) | Inhibiting lymphocyte infiltration | Elkind | 2020 | USA Europe | 300mg Natalizumab (n=91) 600mg Natalizumab (n=92) Placebo(n=94) | ≤9 or >9 to ≤24 hours | 300 or 600 mg | Intravenously | Similar | Similar | – | Similar | (226) |
| S1PR agonist (fingolimod) | Inhibiting lymphocyte infiltration | Fu | 2014 | China | Fingolimod (n=11) Control (n=11) | Within 72 hours after onset; 3 days | 0.5mg | Orally | More good outcome | No | Less | No serious event | (227) |
| S1PR agonist (fingolimod) | Inhibiting lymphocyte infiltration | Zhu | 2015 | China | Fingolimod (n=25) Control (n=22) | Within 4.5 hours after onset; 3 days | 0.5mg | Orally | More good outcome | – | Less | No serious event | (228) |
| S1PR agonist (fingolimod) | Inhibiting lymphocyte infiltration | Tian | 2018 | China | Fingolimod (n=23) Control (n=23) | 4.5-6 hours after onset; 3 days | 0.5mg | Orally | More good outcome | No death | Less | No serious event | (226) |
| Resveratrol | Regulating lymphocyte subsets | Chen | 2016 | China | Resveratrol (n=154) Placebo (n=158) | Within 4 hours after onset | 2.5 mg/kg | Intravenously | Only 24 hours NIHSS score is evaluated, Resveratrol reduce NIHSS score at 24 hours | (229) | |||
| Atorvastatin | Regulating lymphocyte subsets | Muscari | 2011 | Italy | Atorvastatin (n=31) Placebo (n=31) | Within 24 hours after onset; 7 days | 80mg | Orally | More good outcome | Similar | Similar | Similar | (230) |
| Rosuvastatin | Inhibiting microglia activation | Heo | 2016 | Korea | Rosuvastatin (n=155) Placebo (n=159) | Within 66 hours after onset; 14 days | 20 mg | Orally | – | Similar | Similar | Similar | (231) |
| Minocycline | Inhibiting immune cells activation | Westphal | 2007 | Israel | Minocycline (n=74) Placebo (n=77) | 6-24 hours after stroke onset; 5 days | 200 mg | Orally | More good outcome | Similar | – | Similar | (232) |
| IL-1 receptor antagonist (rhIL-1ra) | Inhibiting IL-1 | Emsley | 2005 | UK | rhIL-1ra (n=17) Placebo (n=17) | Within 6 hours after onset; 3 days | LB: 100mg; MB: 2mg/kg/h | Intravenously | More good outcome in cortical infarcts patients | Similar | Less in cortical infarcts patients | Similar | (233) |
| IL-1 Receptor Antagonist (IL-1Ra) | Inhibiting IL-1 | Smith | 2018 | UK | IL-1Ra (n=39) Placebo (n=41) | Within 5 hours after onset; 3 days | 100 mg twice daily | subcutaneously | Similar | Similar | Similar | Similar | (234) |
*not mentioned in the study.
AIS, acute ischemic stroke; mRS, modified ed Rankin Scale; ΔSSS, the Scandinavian Stroke Scale; mBI, modified Barthel Index; NIHSS, the National Institute of Health Stroke Scale; ICAM-1, intercellular adhesion molecule-1; USA, The United States of America; LB, loading bonus; MB: maintenance bolus; RCT, Randomized Controlled Trial; MAC-1, macrophage-1 antigen; UK, The United Kingdom; S1PR, sphingosine 1-phosphate receptor; rhIL-1ra, recombinant interleukin-1 receptor antagonist.