ESCAPE

Clinical Question

Does rapid endovascular treatment improve functional outcomes in patients with acute ischemic stroke who have a small infarct core, proximal vessel occlusion, and good collateral circulation?

Inclusion Criteria

• Adult patients (age ≥18, NO upper age limit — ESCAPE was unique in including patients >80 years).
• Acute ischemic stroke with a disabling neurological deficit (no specific NIHSS eligibility cutoff was specified in the protocol).
• Pre-stroke functional independence (Barthel Index ≥90).
• Proximal anterior circulation occlusion confirmed on CTA: intracranial ICA, M1 MCA, or M2 MCA segment.
• Small infarct core: ASPECTS 6–10 on non-contrast CT (no large established infarct).
• Moderate-to-good collateral circulation: ≥50% MCA pial arterial filling on multiphase CTA — ESCAPE was the FIRST major thrombectomy trial to require collateral assessment as an imaging selection criterion.
• Enrollment within 12 hours of symptom onset (though most patients treated within 6 hours).

Exclusion Criteria

• Large infarct core (ASPECTS <6 on non-contrast CT).
• Poor collateral circulation (<50% MCA pial filling on multiphase CTA).
• Posterior circulation occlusion (basilar, vertebral, PCA).
• Distal vessel occlusion not amenable to mechanical thrombectomy (M3 or beyond).
• Inability to meet rapid workflow time targets (CT-to-groin-puncture >60 min goal).
• Inability to achieve femoral access or navigate to the target vessel.
• Pre-existing disability (Barthel Index <90).
• Known contrast allergy or severe renal impairment precluding CTA.
• (Note: Deferred consent was permitted where allowed by jurisdiction; 56 participants [17.8%] were enrolled under deferred consent when they lacked capacity and a legally authorized representative was unavailable.)

Baseline Characteristics

Arms

Outcomes

Criticisms

• Stopped early after 316 of planned 500 patients — while ethically necessary given overwhelming benefit, early stopping may overestimate treatment effect (the 'stopping bias' of interim analyses).
• No screening logs maintained — cannot estimate what proportion of stroke patients were eligible, making it impossible to determine the real-world applicability of ESCAPE's strict imaging criteria.
• Limited to selected endovascular centers with efficient workflows — the median 84-minute CT-to-reperfusion time is exceptionally fast and may not be achievable at most centers, limiting generalizability.
• Imaging protocol violations in 8.3% of participants — some patients were randomized without complete adherence to the ASPECTS + collateral criteria.
• Multiphase CTA for collateral assessment was a novel, non-validated technique at the time — while subsequently adopted widely, the learning curve and inter-reader variability were not fully characterized.
• PROBE design (open-label treatment, blinded outcome assessment) — treating physicians knew allocation, potentially introducing placebo/nocebo effects in post-procedural care decisions.
• Small number treated beyond 6 hours — while the 12-hour window was allowed, most patients were treated within 6 hours. The extended window benefit was later definitively established by DAWN and DEFUSE 3 using different imaging selection.
• Control group received IV alteplase in 78.7% — higher than some other thrombectomy trials. This may have attenuated the treatment difference by providing some recanalization in controls.
• Predominantly stent retriever era — most procedures used Solitaire FR. Modern aspiration techniques, combined approaches, and newer devices may achieve different outcomes.

Funding

Supported by Covidien through an unrestricted grant to the University of Calgary. Also supported by the University of Calgary (Hotchkiss Brain Institute, Department of Clinical Neurosciences and Calgary Stroke Program, Department of Radiology); Alberta Innovates-Health Solutions; the Heart and Stroke Foundation of Canada; and Alberta Health Services.