PDF: MR CLEAN
(2015)Objective
To assess whether mechanical thrombectomy treatment in addition to usual care improves functional outcomes in patients with acute ischemic stroke due to proximal anterior circulation occlusion.
Study Summary
Intervention
Mechanical thrombectomy (mainly retrievable stents) with or without intraarterial thrombolytics, in addition to standard care including IV alteplase.
Inclusion Criteria
Adults with acute ischemic stroke caused by intracranial occlusion in the anterior circulation (ICA, M1, M2), confirmed on imaging, eligible for intraarterial therapy within 6 hours of symptom onset.
Study Design
Arms: Mecahnical thrombectomy Treatment + Usual Care vs. Usual Care Alone
Patients per Arm: Intervention: 233, Control: 267
Outcome
Bottom Line
Intraarterial treatment with modern devices significantly improved functional outcomes in patients with anterior circulation large vessel occlusion compared to standard care alone.
Major Points
- First positive RCT demonstrating benefit of endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion — published December 2014, catalyzed 4 subsequent positive trials (ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT).
- Eligible vessels: proximal anterior circulation occlusion — intracranial ICA, MCA M1 segment, or MCA M2 segment — confirmed on CTA, MRA, or DSA.
- 500 patients randomized 1:1 at 16 Dutch centers. 89% of intervention group and 87% of control group received IV tPA — one of the highest co-treatment rates in thrombectomy trials.
- Median time from stroke onset to groin puncture: 260 minutes (4.3 hours). Median onset to randomization: 204 minutes.
- Primary outcome (ordinal mRS shift at 90 days): common OR 1.67 (95% CI 1.21–2.30, P=0.001). Functional independence (mRS 0–2): 32.6% vs 19.1% (absolute difference 13.5%, NNT ≈ 7.4).
- Successful reperfusion (mTICI 2b–3): 58.7%. Recanalization at 24 hours: 58.7% vs 41.9% (P=0.007).
- No significant increase in sICH (7.7% vs 6.4%) or 90-day mortality (18.9% vs 18.4%).
- Devices used: predominantly retrievable stents (Solitaire in ~60%, Trevo in ~15%), with some patients receiving intra-arterial thrombolytics or older devices (Merci, Penumbra).
- Pragmatic design — no advanced imaging selection (CTP or MRI perfusion) required, no ASPECTS cutoff mandated, M2 occlusions included.
Study Design
- Study Type
- Multicenter, randomized, open-label, blinded endpoint (PROBE) trial
- Randomization
- Yes
- Blinding
- Blinded endpoint assessment
- Sample Size
- 500
- Follow-up
- 90 days
- Centers
- 16
- Countries
- Netherlands
Primary Outcome
Definition: Distribution of scores on the modified Rankin Scale (mRS) at 90 days (ordinal shift analysis)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| mRS 0–2 in 19.1% | mRS 0–2 in 32.6% | - (1.14–2.38 (common OR 1.67)) | 0.001 |
Limitations & Criticisms
- Open-label (PROBE) design introduces potential bias despite blinded outcome assessment.
- Relatively long onset-to-groin puncture (260 min median) compared to later trials (ESCAPE: 185 min, SWIFT PRIME: 224 min) — reflects real-world Netherlands workflow in 2010–2014.
- Pragmatic design with no ASPECTS cutoff — included patients with large cores who may not benefit, potentially diluting treatment effect.
- Multiple device types used (stent retrievers, aspiration, IA lytics) — cannot isolate which technique was most effective.
- Only Netherlands sites enrolled — may not generalize to other healthcare systems.
- Lower absolute benefit (13.5%) than ESCAPE (23.7%) or DAWN (36%) — likely due to less stringent imaging selection.
- M2 occlusions included (~8%) but too few for meaningful subgroup analysis.
- No crossover permitted in control group — some control patients may have benefited from rescue thrombectomy.
Citation
Dippel DWJ, Majoie CBLM, Roos YBWEM, et al. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med. 2015;372(1):11–20.