MR CLEAN-NO IV Trial: Direct EVT in European Alteplase-Eligible Patients
In patients presenting directly to an EVT-capable center who are eligible for both IV alteplase and thrombectomy, does direct EVT produce superior or non-inferior outcomes to alteplase 0.9 mg/kg plus EVT?
LeCouffe et al. (NEJM 2021) · doi:10.1056/NEJMoa2107727 · 539 patients
Population
Included
- Age 18 or older
- Direct presentation at an EVT-capable center
- Anterior circulation LVO (intracranial ICA, M1, or proximal M2)
- Eligible for IV alteplase within 4.5 hours of symptom onset
- Eligible for endovascular treatment
- Pre-stroke mRS 0 to 2
- Age 18 years or older
- Acute ischemic stroke due to an intracranial proximal occlusion of the anterior circulation (intracranial internal carotid artery, the first segment of the middle cerebral artery [M1], or the proximal second segment [M2]) on CT angiography or MR angiography
- Eligible for both EVT and intravenous alteplase administration within 4.5 hours after symptom onset according to local guidelines
- Admitted directly to a center that performed EVT (directly presenting; mothership)
- Score of 2 or more on the NIHSS (range 0–42)
Excluded
- Contraindication to IV alteplase
- Transferred from a non-EVT center
- Pre-stroke mRS greater than 2
- Presentation beyond 4.5 hours from symptom onset
Per protocol (alteplase contraindications and standard EVT exclusions)
- Any contraindication to intravenous alteplase per current guidelines
- Pre-existing conditions precluding EVT or alteplase as defined in the detailed protocol (full inclusion/exclusion criteria provided in the trial protocol)
Source: LeCouffe et al., NEJM 2021;385:1833-44 (MR CLEAN-NO IV); ISRCTN80619088· Retrieved 2026-06-08
Superiority and non-inferiority: both not demonstrated
MR CLEAN-NO IV tested both superiority and non-inferiority of direct EVT vs alteplase 0.9 mg/kg plus EVT. Neither was met (adjusted common OR 0.84, 95% CI 0.62-1.15, P = 0.28). The point estimate numerically favors bridging therapy; median mRS was 3 (direct EVT) vs 2 (bridging).
Primary Outcome — mRS Ordinal Shift at 90 Days
Direct presenters at EVT-capable centers within 4.5 h
mRS Ordinal Shift at 90 Days
cOR 0.84
95% CI 0.62 to 1.15 · P = 0.28
Median mRS — Direct EVT
3
Median mRS — Bridging
2
Mortality: 20.5% (direct EVT) vs 15.8% (bridging) · sICH: 5.9% vs 5.3%
Study Arms
- Agent
- Endovascular thrombectomy alone (no preceding IV alteplase)
- Route
- Endovascular
- Co-interventions
- EVT without preceding alteplase, with any CE-approved stent retriever; suction catheters allowed as rescue; intra-arterial alteplase permitted at interventionist discretion (max 30 mg); rescue IV alteplase 0.9 mg/kg permitted if incomplete reperfusion (eTICI 0/1/2A) and within 4.5 h of onset.
EVT-alone group; rescue IV alteplase 0.9 mg/kg allowed for incomplete reperfusion within 4.5 h (LeCouffe NEJM 2021 p.1835).
- Agent
- IV alteplase + endovascular thrombectomy
- Dose
- 0.9 mg/kg (max 90 mg)
- Route
- IV (10% bolus, 90% over 1 h) then endovascular
- Co-interventions
- IV alteplase 0.9 mg/kg (max 90 mg), 10% bolus + 90% over 1 h, before EVT; EVT may start before end of infusion per guidelines; any CE-approved stent retriever; suction catheters as rescue; intra-arterial alteplase at discretion (max 30 mg).
Usual-care group received IV alteplase 0.9 mg/kg before EVT (LeCouffe NEJM 2021 p.1835).
Trial Design
Type
- Open-label multicenter European randomized trial
- Direct EVT vs alteplase followed by EVT
- Direct-to-EVT-center patients eligible for both treatments
- Tested superiority and noninferiority of EVT alone
Timeline
Conducted across Europe
N
539
Enrollment
539 patients across European centers. Open-label randomized trial. Enrolled 2017 to 2020. Alteplase dose in bridging arm: 0.9 mg/kg (standard Western dose). Published NEJM 2021.
Bedside Pearl
Even at an EVT-capable center with thrombectomy minutes away, give IV alteplase 0.9 mg/kg first if the patient is eligible. MR CLEAN-NO IV showed numerically worse functional outcomes and higher mortality without alteplase, with the entire point estimate favoring bridging.