ESCAPE (Stroke)

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Goyal M, et al. "Randomized assessment of rapid endovascular treatment of ischemic stroke". The New England Journal of Medicine. 2015. 372(11):1019-1030.
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Clinical Question

Does endovascular thrombectomy benefit acute ischemic stroke patients with a small infarct, a proximal vessel occlusion, and appropriate collateral circulation?

Bottom Line

Acute ischemic stroke patients with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation benefit from endovascular thrombectomy in the context of fast and efficient workflow, innovative imaging, and effective thrombectomy devices.

Major Points

The PROACT II study [1] demonstrated a benefit to endovascular thrombectomy for patients with occlusion of the middle cerebral artery. However, several subsequent trials (IMS III, SYNTHESIS, MR RESCUE) did not corroborate this benefit [2] [3] [4]. More recently, some trials have shown that endovascular thrombectomy is beneficial in context of proof of proximal vessel occlusion[5], small infarct core [6] [7] [8], fast recanalization, [9] [10] and high reperfusion rates [11] [12] [13]. These recent studies also suggest that modern retrievable stents are better than the previous generation of devices [14] [15].

This study aimed to determine whether endovascular thrombectomy would be beneficial with the use of modern retrievable stents and careful patient selection. The trial was stopped early because of efficacy. In total, 238 acute ischemic stroke patients with a small infarct, proximal intracranial occlusion in the anterior circulation, and appropriate collateral circulation were randomized to receive standard care plus endovascular thrombectomy or standard care alone. In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. Endovascular thrombectomy resulted in better functional outcome and reduced mortality. The rate of symptomatic intracerebral hemorrhage did not differ. In summary, among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular thrombectomy is beneficial.

Limitations of the study include early discontinuation of the trial and small sample size, a very rigorous selection criteria that impairs generalizability, slow enrolment, and efficiency/expertise that is difficult to generalize to most centers.

Guidelines

2015 AHA/ASA Focused Update of the 2013 Guidelines [16]
  • Endovascular therapy with a stent retriever is recommended for patients who meet all of the following criteria (Class I; Level of Evidence A):
    • (a) prestroke mRS 0 to 1,
    • (b) acute ischemic stroke receiving intravenous r-tPA within 4.5 hours of onset,
    • (c) causative occlusion of the internal carotid artery or proximal MCA (M1),
    • (d) age ≥18 years,
    • (e) NIHSS score ≥6,
    • (f) ASPECTS ≥6, and
    • (g) treatment can be initiated within 6 hours of symptom onset

Design

  • Multicenter, prospective, randomized controlled trial
  • N=315
    • Intervention (n=165)
    • Control (n=150)
    • One participant who was randomized to the control group received thrombectomy. 14 participants who were randomized to thrombectomy did not receive intervention.
  • Setting: 22 centers: Canada (11 centers), United States (6), South Korea (3), Ireland (1), and United Kingdom (1)
  • Enrollment: February 2013 through October 2014
  • Primary outcome: Modified Rankin scale score at 90 days
  • Secondary outcomes and adverse events: Early recanalization and reperfusion, intracranial hemorrhage, angiographic complications, neurologic disability at 90 days, and death.
  • Follow-up: 4 participants (1.3%) were lost to follow-up.

Full protocol published in 2014 [17]

Population

Inclusion Criteria

Clinical Criteria

  • Acute ischemic stroke
  • Age ≥18
  • Time since onset <12 hours.
  • NIHSS >5
  • Pre-stroke modified Barthel Index >90.
    • From an independent living arrangement.

Imaging Criteria

  • Symptomatic occlusion at:
    • Carotid T/L, M1, or M1-equivalent (2 or more M2s).
  • Initiation of endovascular treatment within 60 minutes and time to first recanalization of 90 minutes of imaging.

Exclusion Criteria

  • Moderate/large infarct core
  • No or minimal collateral circulation
  • Groin puncture is not possible within 60 minutes
  • No femoral pulses or very difficult endovascular access
  • Pregnancy
  • Severe contrast allergy
  • Suspected intracranial dissection
  • Chronic intracranial occlusion
  • Severe or fatal comorbid illness

Baseline Characteristics

Comparisons are intervention vs. control

  • Demographic characteristics:
    • Age (yr):
      • Median: 71 vs. 70
      • Interquartile range: 60–81 vs. 60–81
    • Female sex: 86 (52.1%) vs. 79 (52.7%)
    • White race: 144 (87.3%) vs. 131 (87.3%)
  • Medical history:
    • Hypertension: 105 (63.6%) vs. 108 (72.0%)
    • Diabetes mellitus: 33 (20.0%) vs. 39 (26.0%)
    • Atrial fibrillation: 61 (37.0%) vs. 60 (40.0%)
  • Clinical characteristics:
    • NIHSS score:
      • Median: 16 vs. 17
      • Interquartile range: 13–20 vs. 12–20
    • Systolic blood pressure (mm Hg):
      • Median: 147 vs. 146
      • Interquartile range: 131–159 vs. 125–169
    • Glucose level (mmol/liter):
      • Median: 6.6 vs. 6.7
      • Interquartile range: 5.8–7.7 vs. 5.7–7.8
  • Imaging characteristics:
    • ASPECTS on CT: median (interquartile range): 9 (8–10) vs. 9 (8–10)
    • Location of occlusion on CTA:
      • ICA with involvement of the M1 segment: 45/163 (27.6%) vs. 39/147 (26.5%)
      • M1 or all M2 segments: 111/163 (68.1%) vs. 105/147 (71.4%)
      • Single M2 segment: 6/163 (3.7%) vs. 3/147 (2.0%)
    • Ipsilateral cervical carotid occlusion: 21 (12.7%) vs. 19 (12.7%)
  • Process times (min):
    • Stroke onset to randomization:
      • Median: 169 vs. 172
      • Interquartile range: 117–285 vs. 119–284
    • Stroke onset to study CT:
      • Median: 134 vs. 136
      • Interquartile range: 77–247 vs. 76–238
    • Stroke onset to start of IV alteplase:
      • Median: 110 vs. 125
      • Interquartile range: 80–142 vs. 89–183
    • Study CT to groin puncture:
      • Median: 51 vs. NA
      • Interquartile range: 39–68 vs. NA
    • Study CT to first reperfusion:
      • Median: 84 vs. NA
      • Interquartile range: 65–115 vs. NA
    • Stroke onset to first reperfusion:
      • Median: 241 vs. NA
      • Interquartile range: 176–359 vs. NA
  • Treatment with IV alteplase: 120 (72.7%) vs. 118 (78.7%)

Interventions

  • Participants in both groups received intravenous alteplase within 4.5 hours if eligible.
  • The control group received the current standard of care as described in the Canadian or local guidelines for the management of acute stroke.
  • Participants in the intervention group underwent rapid cerebral angiogram, and thrombectomy by a neurointerventionist using retrievable stents and suction through a balloon guide catheter whenever possible.

Outcomes

Comparisons are thrombectomy vs. control

Primary Outcomes

Modified Rankin score at 90 days
Common odds ratio 3.1; 95% CI 2.0–4.7

Secondary Outcomes

Modified Rankin score of 0–2 at 90 days
87/164 (53.0%) vs. 43/147 (29.3%) (Difference 23.8; 95% CI 13.2–34.4) (Rate ratio 1.7; 95% CI 1.3–2.2)
NIHSS score of 0–2 at 90 days
79/153 (51.6%) vs. 31/134 (23.1%) (Difference 28.4; 95% CI 17.8–39.2) (Rate ratio 2.1; 95% CI 1.5–3.0)
Barthel Index score of 95–100 at 90 days
94/163 (57.7%) vs. 49/146 (33.6%) (Difference 24.1; 95% CI 13.3–34.9) (Rate ratio 1.7; 95% CI 1.3–2.2)
TICI score of 2b or 3 at final angiogram
113/156 (72.4%) vs. NA
Modified AOL score of 2 or 3
NA vs. 43/138 (31.2%)
NIHSS score at 24 hours, median (interquartile range)
6 (3–14) vs. 13 (6–18) (Beta coefficient 4.1; 95% CI 2.6–5.6)
NIHSS score at 90 days, median(interquartile range)
2 (1–8) vs. 8 (3–19) (Beta coefficient 6.5; 95% CI 3.5–9.6)
EQ-5D visual-analogue scale score at 90 days, median (interquartile range)
80 (60–90) vs. 65 (50–80) (Beta coefficient 9.9; 95% CI 3.8–16.0)

Subgroup Analysis

Prespecified subgroups included age, sex, baseline NIHSS score, baseline ASPECTS, location of vessel occlusion, and alteplase treatment. All subgroups favored the intervention, but the proportion of good outcomes varied among subgroups.

Adverse Events

Death
17/164 (10.4%) vs. 28/147 (19.0%) (Difference 8.6; 95% CI 0.8-16.6) (Rate Ratio 0.5; 95% CI 0.3-0.8)
Large or malignant MCA stroke
8 (4.8%) vs. 16 (10.7%) (Difference 5.8; 95% CI 0.1-11.7) (Rate Ratio 0.3; 95% CI 0.1-0.7)
Symptomatic intracerebral hemorrhage
6 (3.6%) vs. 4 (2.7%) (Difference 1.0; 95% CI −2.9 to 4.8) (Rate Ratio 1.2; 95% CI 0.3-4.6)
Hematoma at access site
3 (1.8%) vs. 0
Perforation of MCA
1 (0.6%) vs. 0

Criticisms

  • The trial had early discontinuation, a small sample size, and slow enrolment
  • The study did not document screening logs so it is unknown how many patients were deemed ineligible based on the strict inclusion criteria.
  • The treatment centers offer advanced workflow and imaging techniques that aren't generalizable to all tertiary care centers.

Funding

The trial was funded by Covidien, the University of Calgary, Alberta Innovates–Health Solutions, the Heart and Stroke Foundation of Canada, and Alberta Health Services.

ClinicalTrials.gov Identifier: NCT01778335 [18]

Further Reading

  1. Furlan A et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 1999. 282:2003-11.
  2. Broderick JP et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N. Engl. J. Med. 2013. 368:893-903.
  3. Ciccone A & Valvassori L Endovascular treatment for acute ischemic stroke. N. Engl. J. Med. 2013. 368:2433-4.
  4. Kidwell CS et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N. Engl. J. Med. 2013. 368:914-23.
  5. Demchuk AM et al. Recanalization and clinical outcome of occlusion sites at baseline CT angiography in the Interventional Management of Stroke III trial. Radiology 2014. 273:202-10.
  6. Menon BK et al. Multiphase CT Angiography: A New Tool for the Imaging Triage of Patients with Acute Ischemic Stroke. Radiology 2015. 275:510-20.
  7. von Kummer R et al. Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol 1994. 15:9-15; discussion 16-8.
  8. Yoo AJ et al. Infarct volume is a pivotal biomarker after intra-arterial stroke therapy. Stroke 2012. 43:1323-30.
  9. Goyal M et al. Evaluation of interval times from onset to reperfusion in patients undergoing endovascular therapy in the Interventional Management of Stroke III trial. Circulation 2014. 130:265-72.
  10. Menon BK et al. Optimal workflow and process-based performance measures for endovascular therapy in acute ischemic stroke: analysis of the Solitaire FR thrombectomy for acute revascularization study. Stroke 2014. 45:2024-9.
  11. Saver JL et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012. 380:1241-9.
  12. Nogueira RG et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012. 380:1231-40.
  13. Pereira VM et al. Prospective, multicenter, single-arm study of mechanical thrombectomy using Solitaire Flow Restoration in acute ischemic stroke. Stroke 2013. 44:2802-7.
  14. Saver JL et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012. 380:1241-9.
  15. Nogueira RG et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012. 380:1231-40.
  16. Powers WJ et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015. 46:3020-35.
  17. Demchuk AM et al. Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE) trial: methodology. Int J Stroke 2015. 10:429-38.
  18. https://www.clinicaltrials.gov/ct2/show/NCT01778335?term=NCT01778335&rank=1