MR CLEAN Trial: Intra-arterial Treatment for Anterior Circulation LVO
In patients with proximal anterior circulation large-vessel occlusion treatable within 6 hours, does intra-arterial treatment added to usual care improve functional outcome at 90 days compared with usual care alone?
Berkhemer et al. (NEJM 2015) · doi:10.1056/NEJMoa1411587 · 500 patients
Population
Included
- Age 18 years or older
- Acute ischemic stroke with NIHSS of 2 or more
- Proximal arterial occlusion in the anterior circulation (intracranial ICA, M1 or M2 of MCA, A1 or A2 of ACA) confirmed on CTA, MRA, or DSA
- Intra-arterial treatment feasible within 6 hours of symptom onset
- Pre-stroke functional independence (mRS 0 to 2 by history)
- Age 18 years or older (no upper age limit)
- Acute ischemic stroke caused by an intracranial arterial occlusion in the anterior circulation
- A proximal intracranial occlusion of the distal intracranial ICA, MCA (M1 or M2), or anterior cerebral artery (A1 or A2), established with CTA, MRA, or DSA
- A score of 2 or higher on the NIHSS (range 0 to 42)
- Intra-arterial treatment possible within 6 hours after symptom onset
- Inclusion of patients with an additional extracranial ICA occlusion or dissection left to the treating physician's judgment
- Written informed consent provided by all patients or their legal representatives before randomization
Excluded
- Onset of stroke symptoms more than 6 hours before groin puncture
- No demonstrable proximal anterior circulation occlusion on vessel imaging
- Severe pre-existing dependency (mRS greater than 2)
- Pregnancy or breastfeeding
- Standard contraindications to endovascular treatment, including uncorrectable coagulopathy
- Detailed enumerated exclusion criteria are specified in the study protocol / Supplementary Appendix and are not reproduced in the main-text Methods.
Source: Berkhemer et al., NEJM 2015;372:11-20 (MR CLEAN); NTR1804 / ISRCTN10888758· Retrieved 2026-06-08
Primary Outcome — mRS Distribution at 90 Days
All randomized patients (anterior circulation LVO)
mRS 0-2 at 90 Days
Study Arms
- Agent
- Intra-arterial therapy at interventionist's discretion: mechanical thrombectomy (retrievable stent, thrombus retraction, aspiration, or wire disruption) and/or intra-arterial thrombolysis (alteplase or urokinase). Retrievable stents used in 190/233 (81.5%).
- Route
- Endovascular (intra-arterial)
- Frequency
- Single procedure: microcatheter to the occlusion, then thrombolytic delivery, mechanical thrombectomy, or both. Method left to the local interventionist.
- Duration
- One-time procedure
- Co-interventions
- + usual care, which could include IV alteplase when eligible (89.0% of all randomized received IV alteplase before randomization). If IV alteplase given, IA thrombolytic capped at 30 mg alteplase or 400,000 IU urokinase (otherwise max 90 mg / 1,200,000 IU).
Technique + IA-dose caps from Berkhemer NEJM 2015 p.13. Only approved devices, operator ≥5 prior procedures with that device type. Device-agnostic; heterogeneous device generations (limits generalizability to modern stent retrievers). Any IA therapy 196/233 (84.1%); GA 37.8%; acute cervical carotid stenting 12.9%. Source: NTR1804 / ISRCTN10888758 (no CT.gov NCT).
- Agent
- Usual care per Dutch acute-stroke practice (no protocol-mandated intra-arterial treatment)
- Route
- Medical
- Co-interventions
- + usual care, which could include IV alteplase when eligible (90.6% of control received IV alteplase). No protocol-mandated intra-arterial therapy.
Control = usual care alone (Berkhemer NEJM 2015 p.12). Main text characterizes 'usual care' only as care that could include IV alteplase; granular medical-management (BP/glucose/antithrombotic) is appendix-deferred. 1/267 control (0.4%) crossed over to IA treatment. Source: NTR1804 / ISRCTN10888758.
Trial Design
Type
- Pragmatic phase 3 randomized trial
- Open-label with blinded endpoint assessment
- Intra-arterial therapy plus usual care vs usual care alone
- Treatment possible within 6 hours of onset
Timeline
Enrolled at 16 Dutch centers
N
500
Enrollment
Pragmatic phase 3 RCT enrolling 500 patients across 16 Dutch centers between December 2010 and June 2014 (Berkhemer NEJM 2015).
Bedside Pearl
When CTA confirms a proximal anterior circulation occlusion within 6 hours and the patient was independent before the stroke, MR CLEAN is consistent with proceeding to thrombectomy without waiting for IV alteplase to finish, in line with current AHA/ASA practice. The absolute gain in functional independence was 13.5 percentage points (NNT about 7, derived from the secondary mRS 0-2 outcome; the protocol-defined primary was the ordinal mRS shift).
See also