Table 1.
Summary of Endovascular Trials.
| Trial | Study Design | Study Population | Main Results |
|---|---|---|---|
| PROACT 230 | PROBE, IA r-proUK + heparin vs heparin only | AIS <6 hours from onset, age 18-85, angiographically proven MCA occlusion, no hemorrhage or major early infarction signs; n = 180 | 40% of r-proUK vs 25% control had mRS ≤2 at 90 days (P = .04), mortality 27% r-proUK vs 25% control, MCA recanalization 66% r-proUK vs 18% control (P < .001), sICH at 24 hours 10% r-proUK vs 2% control (P = .06) |
| MR RESCUE56 | PROBE, IA mechanical thrombectomy (Merci Retriever or Penumbra System) vs standard care | AIS <8 hours from onset, age 18-85, NIHSS 6-29, large artery anterior circulation, including “tPA failure” if persistent target occlusion identified; n = 118 | Mean 90-day mRS did not differ embolectomy vs standard care (3.9 vs 3.9, P = .99). No interaction between pretreatment imaging (“penumbra”) and outcome between groups (P = .14) |
| IMS39 | Multicenter open-label, single-arm pilot of feasibility, and safety of combined IV and IA tPA as compared to NINDS patient data | AIS <3 hours from onset age 18-80, NIHSS ≥10, reduced-dose tPA in all patients (0.6 mg/kg, max 60 mg) and IA tPA 22 mg infusion if clot identified in any intracranial large artery; n = 80 | Three-month mortality 16% in IMS-treated patients vs 24% and 21% in placebo and tPA NINDS patients (nonsignificant). sICH was 6.3% in IMS-treated patients, similar to NINDS tPA (6.6%). As compared to NINDS placebo, IMS-treated patients 90-day mRS 0-1 (OR 2.26, 95% CI 1.15-4.47) and mRS 0-2 (OR 2.18, 95% CI 1.20-3.99). As compared to NINDS tPA, IMS-treated patients 90-day mRS 0-1 (OR 1.00, 95% CI 0.51-1.96) and mRS 0-2 (OR 1.28, 95% CI 0.70-2.33) |
| IMS II57 | Multicenter open-label, single-arm pilot of feasibility, and safety of combined IV and IA tPA as compared to NINDS patient data; only difference from IMS was the use of an ultrasound-emitting microcatheter | AIS <3 hours from onset age 18-80, NIHSS ≥10, reduced-dose tPA in all patients (0.6 mg/kg, max 60 mg) and IA tPA 22 mg infusion if clot identified in any intracranial large artery; n = 80 | Three-month mortality 16% in IMS-treated patients vs 24% and 21% in placebo and tPA NINDS patients (nonsignificant). sICH was not statistically significantly different in IMS-treated patients (9.9%) compared to NINDS tPA (6.6%). As compared to NINDS placebo, IMS-treated patients 90-day mRS 0-1 (OR 2.78, 95% CI 1.46-5.31) and mRS 0-2 (OR 2.82, 95% CI 1.54-5.16). As compared to NINDS tPA, IMS-treated patients 90-day mRS 0-1 (OR 1.36, 95% CI 0.72-2.56) and mRS 0-2 (OR 1.74, 95% CI 0.95-3.19) |
| IMS III26 | Phase III, international, multicenter, randomized, open-label, and blinded outcome combined IV and IA tPA (including ultrasound-emitting microcatheter) as compared to standard tPA (2:1) | AIS <3 hours from onset age 18-82, NIHSS ≥10 (NIHSS ≥8 with CTA evidence of large artery clot), IV + IA tPA per IMS/IMS II vs standard dose tPA; n = 656 | Ninety-day mRS not different treatment (40.8%) vs control (38.7%), 95% CI (-6.1-9.7). 90-Day mortality was similar between treatment and control groups (19.1% vs 21.6%, P = .52). sICH within 30 hours of tPA was similar between treatment and control groups (6.2% vs 5.9%, P = .83) |
| SYNTHESIS55 | “Pragmatic” multicenter, open-label blinded end point of primary IA therapy (tPA, mechanical, or both) vs IV tPA | AIS <4.5 hours from onset age 18-80; n = 362 | Three-month mRS 0-1 no difference between IA (30.4%) vs IV tPA (34.8%), OR 0.71 95% CI (0.44-1.14). Onset to start of treatment 3.75 hours for IA vs 2.75 hours for IV tPA (P < .001) |
| MR CLEAN40 | “Pragmatic” PROBE, IA intervention (thrombolysis and/or mechanical extraction) plus usual care (including IV tPA) vs usual care alone. | AIS <6 hours from onset, age 18+, Dutch population, angiographically proven anterior circulation occlusion, NIHSS ≥2; n = 500 | Ninety-day mRS 0-2 in 32.6% of intervention vs 19.1% of usual care patients (95% CI 5.9-21.2). No significant differences in mortality or sICH between groups. 89% of patients received IV tPA and retrievable stents were used in 81.5% of patients assigned to intervention |
| EXTEND-IA43 | Investigator-initiated PROBE, IA intervention + IV tPA vs IV tPA alone (1:1) | AIS within 4.5 hours (for IV tPA) of onset, IA initiated within 6 hours of onset and completed within 8 hours of onset, age ≥18, ICA or M1/M2 MCA occlusion, and penumbra imaging pattern; n = 70 | Three-day early recovery (80% vs 37%) and mRS 0-2 (71% vs 40%, P = .01) favored interventional group, no significant differences in rates of death or sICH |
| SWIFT PRIME44–46 | Global multicenter PROBE, IA intervention (Solitaire) + IV tPA vs IV tPA alone (1:1) | AIS within 4.5 hours of onset, IA initiated within 6 hours of onset, intracranial ICA or M1 MCA occlusion, age 18-80, premorbid mRS ≤1, NIHSS 8-29; n = 196 | Ninety-day mRS 0-2 in 60.2% intervention + tPA vs 35.5% in tPA alone (P = .0002), sICH 1% intervention vs 3.1% tPA alone, death at 90 days 9.2% intervention vs 12.4% tPA alone (P = .50) |
| ESCAPE41,42 | Multicenter PROBE, 1:1 endovascular treatment + guideline-based care vs guideline-based care alone | AIS within 12 hours of onset, age ≥18, premorbid BI ≥90, intracranial ICA or M1 MCA occlusion, ASPECTS 6-10; n = 316 | Ninety-day mRS 0-2 53% intervention vs 29.3% control (P < .001), mortality 10.4% intervention vs 19% control (P = .04), sICH 3.6% intervention vs 2.7% control (P = .75). Median time from study CT to first reperfusion = 84 min in intervention group. |
Abbreviations: PROBE, prospective, randomized, open-label, blind end point; IA, intra-arterial; r-proUK, recombinant pro-urokinase; AIS, acute ischemic stroke; MCA, middle cerebral artery; mRS, modified Rankin Scale; sICH, symptomatic intracranial hemorrhage; CI, confidence interval; MR RESCUE, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy; NIHSS, National Institutes of Health Stroke Scale; IV tPA, intravenous tissue plasminogen activator; ICA, internal carotid artery; M1, first segment of MCA; M2, second segment of MCA; BI, Barthel Index; SYNTHESIS Expansion, a Randomized Controlled Trial on Intra-arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke; MR CLEAN, Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; ESCAPE, Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke; EXTEND-IA, Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial; SWIFT PRIME, Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment; NINDS, National Institute of Neurological Disorders and Stroke; CT, computed tomographic; PROACT, Prourokinase in Acute Cerebral Thromboembolism; IMS III, Third Interventional Management of Stroke; OR, odds ratio; ASPECTS, Alberta Stroke Program Early Computed Tomography Score.