DIRECT-MT Trial: Thrombectomy Alone vs Bridging Alteplase
In alteplase-eligible patients with anterior circulation LVO presenting within 4.5 hours, is direct endovascular thrombectomy non-inferior to IV alteplase followed by thrombectomy for 90-day functional outcome?
Yang et al. (NEJM 2020) · doi:10.1056/NEJMoa2001123 · 656 patients
Population
Included
- Age 18 years or older
- Acute ischemic stroke with anterior circulation large vessel occlusion (intracranial ICA, M1, or proximal M2)
- Eligible for IV alteplase per Chinese guidelines
- Endovascular treatment initiable within 4.5 hours of last known well
- NIHSS 2 or greater at presentation
- Pre-stroke mRS 0 or 1
- a clinical diagnosis of acute ischemic stroke
- caused by a large vessel occlusion of the anterior circulation (distal intracranial carotid artery or middle M1/proximal M2 cerebral artery) confirmed by CTA
- CT or MRI ruling out intracranial hemorrhage
- eligible for IVT and IAT (within 4.5 hours after symptom onset)
- a score of at least 2 on the NIH Stroke Scale
- age of 18 years or older
- written informed consent
Excluded
- Contraindication to IV alteplase
- Posterior circulation occlusion
- Pre-existing functional disability (mRS 2 or greater)
- Anticipated delay in EVT initiation beyond 4.5 hours
- Pregnancy
- Life expectancy under 6 months
- Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, i.e. mRS >2
- Any contra-indication for IVT, according to guidelines of the American Heart Association, i.e.: arterial blood pressure exceeding 185/110 mmHg; blood glucose less than 2.7 or over 22.2 mmol/L; cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of recent infarction on neuro-imaging; serious head trauma in the previous 3 months; major surgery or serious trauma in the previous 2 weeks; gastrointestinal or urinary tract hemorrhage in the previous 3 weeks; previous intracerebral hemorrhage; use of anticoagulant with INR exceeding 1.7; known thrombocyte count less than 100 × 10⁹/L; treatment with direct thrombin or factor X inhibitors; treatment with heparin (APTT exceeds the upper limit of normal value) in the previous 48 hours
Source: ClinicalTrials.gov NCT03469206· Retrieved 2026-06-08
Primary Outcome — mRS Ordinal Shift at 90 Days (Non-inferiority)
All randomized patients (anterior circulation LVO, eligible for IV alteplase)
Non-inferiority design
This trial tested whether direct EVT is no worse than bridging alteplase, not whether it is better. A non-inferior result supports equivalence, not superiority. The CI just cleared the pre-specified margin.
Negligible absolute difference
mRS 0-2 at 90 Days
Study Arms
- Agent
- Mechanical thrombectomy with a China-FDA-approved device. Stent retriever primary; aspiration devices secondary if initial reperfusion failed.
- Route
- Endovascular
- Frequency
- Single procedure, initiated within 4.5 h of symptom onset. NO alteplase before or during the procedure.
- Duration
- One-time procedure
- Co-interventions
- Intra-arterial alteplase (max 30 mg) or urokinase (max 400,000 U) accepted as RESCUE therapy in BOTH groups, at treating-physician discretion.
From Yang NEJM 2020 p.1983: 'thrombectomy alone had no alteplase administration before or during the procedure.' Successful reperfusion 79.4%. Source: NCT03469206.
- Agent
- IV alteplase per AHA-ASA and local guidelines, followed by mechanical thrombectomy (stent retriever primary, aspiration secondary)
- Dose
- Alteplase 0.9 mg/kg (maximum 90 mg)
- Route
- IV alteplase + endovascular thrombectomy
- Frequency
- Alteplase 10% bolus then 90% infused over 1 hour; infusion could continue DURING thrombectomy even if revascularization was achieved. Thrombectomy within 4.5 h of onset.
- Duration
- Alteplase 1-hour infusion; thrombectomy one-time procedure
- Co-interventions
- Same IA-alteplase (max 30 mg) / urokinase (max 400,000 U) rescue allowance as the direct arm, both groups.
Verbatim from Yang NEJM 2020 p.1983. Successful reperfusion 84.5%; pre-thrombectomy reperfusion 7.0% (vs 2.4% direct). Source: NCT03469206.
Trial Design
Type
- Multicenter Chinese noninferiority trial
- Thrombectomy alone vs alteplase followed by thrombectomy
- Anterior circulation LVO within 4.5 hours
- Primary analysis based on mRS distribution at 90 days
Timeline
Conducted at 41 tertiary centers
N
656
Enrollment
Multicenter Chinese noninferiority RCT enrolling 656 patients at 41 tertiary centers (Yang NEJM 2020). Open-label with blinded endpoint assessment.
ClinicalTrials.gov
NCT03469206Bedside Pearl
DIRECT-MT met non-inferiority for direct EVT vs bridging in Chinese centers with short door-to-puncture times. Do not extrapolate to systems where transfer delays make pre-EVT reperfusion (lost from 7.0% to 2.4%) clinically meaningful. Continue IV thrombolysis per AHA/ASA recommendations unless local data and workflow support omission.