MR CLEAN-LATE
(2023)Objective
To assess the efficacy and safety of endovascular treatment in patients with anterior circulation ischemic stroke presenting 6-24 hours from symptom onset or last seen well, selected on the basis of collateral flow on CT angiography (CTA).
Study Summary
• All-cause mortality at 90 days did not differ significantly (24% vs 30%; adjusted OR 0.72, 95% CI 0.44-1.18)
• Symptomatic intracranial hemorrhage was more frequent with endovascular treatment (7% vs 2%; adjusted OR 4.59, 95% CI 1.49-14.10)
• Collateral flow on CTA alone is a viable, pragmatic selection criterion for late-window thrombectomy
Intervention
Endovascular treatment (thrombectomy) plus best medical treatment vs best medical treatment alone in the late window (6-24 h).
Inclusion Criteria
Age ≥18 years; ischemic stroke with anterior circulation large-vessel occlusion; presentation 6-24 h from symptom onset or last seen well; collateral flow on CTA (grades 1-3); NIHSS ≥2; not eligible for late-window endovascular treatment per Dutch national guidelines (DAWN/DEFUSE-3 criteria).
Study Design
Arms: Endovascular treatment + best medical treatment (n=255) vs Best medical treatment alone (n=247)
Patients per Arm: 255 vs 247
Outcome
• All-cause mortality: 24% (62/255) vs 30% (74/247); adjusted OR 0.72 (95% CI 0.44-1.18), not statistically significant
• Symptomatic intracranial hemorrhage: 7% (17/255) vs 2% (4/247); adjusted OR 4.59 (95% CI 1.49-14.10)
Bottom Line
In patients with anterior circulation ischemic stroke presenting 6-24 h from symptom onset or last seen well who were not eligible for treatment under DAWN/DEFUSE-3 criteria, endovascular treatment selected by the presence of collateral flow on CTA improved functional outcomes at 90 days, supporting a more pragmatic and inclusive selection strategy that does not require perfusion imaging.
Major Points
- Endovascular treatment produced a favorable shift in 90-day mRS (adjusted common OR 1.67, 95% CI 1.20-2.32)
- Median mRS was 3 (IQR 2-5) with endovascular treatment vs 4 (IQR 2-6) with best medical treatment alone
- Symptomatic intracranial hemorrhage was significantly more common with endovascular treatment (7% vs 2%; adjusted OR 4.59, 95% CI 1.49-14.10)
- All-cause 90-day mortality was numerically lower but not statistically different (24% vs 30%; adjusted OR 0.72, 95% CI 0.44-1.18)
- Selection using CTA collateral flow alone is a viable, pragmatic alternative to perfusion imaging for late-window thrombectomy eligibility
- Findings support extending late-window thrombectomy indications beyond current DAWN/DEFUSE-3 criteria, particularly where perfusion imaging is limited
Study Design
- Study Type
- Multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial (PROBE design)
- Randomization
- Yes
- Blinding
- Open-label with blinded endpoint assessment (PROBE design)
- Sample Size
- 535
- Follow-up
- 90 days
- Centers
- 18
- Countries
- Netherlands
Primary Outcome
Definition: Modified Rankin Scale (mRS) score distribution (ordinal shift analysis)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS 4 (IQR 2-6) | Median mRS 3 (IQR 2-5) | 1.67 (1.20-2.32) |
Limitations & Criticisms
- Open-label design (though endpoint assessment was blinded) may introduce bias in management decisions
- Conducted entirely in the Netherlands, limiting generalisability to other health systems and populations
- Increased risk of symptomatic intracranial hemorrhage with endovascular treatment must be weighed against functional benefit
- Enrollment excluded patients eligible under DAWN/DEFUSE-3 criteria, so results apply to a complementary (not overlapping) population
Citation
Lancet 2023; 401: 1371-80