Table 1.
Randomized clinical trials
| Study | ATTEST [18] | Australian TNK trial [19] | Haley et al. [20] | EXTEND-IA TNK [24•] | NOR-TEST [23] |
|---|---|---|---|---|---|
| Design | RCT phase II | RCT phase IIB | RCT Phase IIB/III | Phase III open-label blinded endpoint RCT | Phase III open-label blinded endpoint RCT |
| Inclusion criteria | Supratentorial AIS |
CTP: penumbra ≥ 20% core + CTA occlusion |
AIS < 3 h | Evidence of proximal LVO on CTA + eligible for EVT | Clinically suspected AIS with measurable deficit on NIHSS + eligible for EVT |
| N | 104 | 75 | 112 | 202 | 1100 |
| TNK dose (mg/kg) (n) | 0.25 (n = 52) |
0.1 (n = 25) 0.25 (n = 25) |
0.1 (n = 31) 0.25 (n = 31) 0.4 (n = 19) |
0.25 mg/kg | 0.4 mg/kg |
| Treatment window | 4.5 h | 6 h | 3 h | < 4.5 h from LKW | < 4.5 h from LKW or from Awakening |
| Imaging selection | NCCT | CTP and CTA | NCCT | CTA/CTP: perfusion mismatch for anterior circulation strokes on CTP; ratio of > 1.2, absolute difference in volume > 10 ml, ischemic core volume < 70 ml * |
NCCT for < 4.5 h from LKW MRI (DWI/FLAIR) mismatch for < 4.5 h from awakening |
| Primary outcome |
Salvaged penumbra 68% TNK p 0.81 68% alteplase |
Reperfusion 79.3% TNK p 0.004 55.4% alteplase NIHSS improvement 8 TNK p < 0.001 3 Alteplase |
90 Day mRS mRS < 2 TNK 0.1 mg/kg: 45.2% TNK 0.25 mg/kg: 48.4% Alteplase 0.9 mg/kg: 41.9% |
Reperfusion > 50% at time of angiogram OR absence of retrievable thrombus at time of the initial angiogram: 22% TNK vs. 10% Alteplase (P = 0.002 for non-inferiority; P = 0.03 for superiority) |
Excellent functional outcome: mRS score 0–1 at 90 days: 64% TNK vs. 63% Alteplase (P = 0.52) |
| sICH |
2% TNK p 0.5 4% alteplase |
4% TNK p 0.33 12% alteplase |
0% 0.1 mg/kg TNK 6.5% 0.25 mg/kg TNK 8% 0.4 mg/kg TNK 3.2% alteplase |
1% in both groups |
Any ICH at 24–48 h: 9% for both sICH at 24–48 h: 3% for TNK 2% for alteplase |
| Conclusion | Outcomes did not differ between groups | TNK had better reperfusion rates and clinical outcomes | TNK 0.4 mg/kg was discarded as inferior |
TNK associated with improved reperfusion and improved functional outcomes No significant difference in number of patients with no/minimal disability at 90 days (mRS < 2) |
Further studies necessary to establish non-inferiority of TNK and safety/efficacy in moderate/severe strokes |
*This criterion was removed after ~80 patients enrolled due to analysis from other trials demonstrating benefit in patients with larger ischemic core volumes