SWIFT DIRECT Trial: Thrombectomy Alone vs Alteplase Plus Thrombectomy
In patients presenting directly to a comprehensive stroke center within 4.5 hours with anterior circulation proximal LVO, does stent-retriever thrombectomy alone produce outcomes non-inferior to alteplase 0.9 mg/kg plus thrombectomy?
Fischer et al. (Lancet 2022) · doi:10.1016/S0140-6736(22)00537-2 · 423 patients
Population
Included
- Age 18 to 80
- Direct presentation at a comprehensive stroke center
- Anterior circulation proximal LVO (ICA or M1)
- NIHSS 2 or greater
- Eligible for IV alteplase within 4.5 hours of symptom onset
- Pre-stroke mRS 0 to 2
- Informed consent as documented by signature
- Age ≥ 18
- Clinical signs consistent with an acute ischemic stroke
- Neurological deficit with a NIHSS of ≥ 5 and < 30 (deficits judged to be clearly disabling at presentation)
- Patient is eligible for intravenous thrombolysis
- Patient is eligible for endovascular treatment
- Randomization no later than 4 hours 15 minutes after stroke symptom onset and initiation of IV t-PA must be started within 4 hours 30 minutes of stroke symptoms onset (onset time is measured from the time when the subject was last seen well)
- Occlusion (TICI 0-1) of the intracranial internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or both confirmed by CT or MR angiography, accessible for MT
- Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) greater than or equal to 4 (≥ 4) based on baseline CT or MR imaging (a region has to have diffusion abnormality in 20% or more of its volume to be considered MR-ASPECTS positive)
Excluded
- Contraindication to IV alteplase
- Posterior circulation occlusion
- M2 or more distal occlusion
- Age greater than 80
- Transferred from non-EVT center
- Pre-stroke mRS greater than 2
- Acute intracranial hemorrhage
- Any contraindication for IV t-PA
- Pre-treatment with IV t-PA
- In-hospital stroke
- Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.
- Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys
- Known current participation in a clinical trial (investigational drug or medical device)
- Renal insufficiency as defined by a serum creatinine > 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) < 30 mL/min or requirement for hemodialysis or peritoneal dialysis
- Severe comorbid condition with life expectancy less than 90 days at baseline
- Known advanced dementia or significant pre-stroke disability (mRS score of ≥2)
- Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)
- Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
- Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
- Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT
- Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
- Radiological confirmed evidence of cerebral vasculitis
- CTA or MRA evidence of carotid artery dissection
- Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA
Source: ClinicalTrials.gov NCT03192332 (SWIFT DIRECT)· Retrieved 2026-06-08
Non-inferiority design: margin not met
SWIFT DIRECT tested whether thrombectomy alone was acceptably close to alteplase plus thrombectomy (NI margin: -10 pp). Non-inferiority was not demonstrated: the adjusted RD was -7.3% (95% CI -14.0% to -0.6%). The entire confidence interval is negative; even the most optimistic estimate favors bridging therapy.
Primary Outcome — mRS 0-2 at 90 Days (Non-inferiority)
Anterior circulation proximal LVO; direct presenters within 4.5 h
Negligible absolute difference
mRS 0-2 at 90 Days
Study Arms
- Agent
- Stent-retriever thrombectomy (no IV alteplase)
- Route
- Endovascular
- Co-interventions
- Thrombectomy initiated as fast as possible with any commercially available Solitaire stent-retriever; no preceding IV alteplase; balloon guide/distal aspiration catheter strongly encouraged; intra-arterial fibrinolytics prohibited; concomitant care per international standards.
Intervention = thrombectomy alone; Solitaire device in both arms; IA fibrinolysis prohibited (Fischer Lancet 2022 p.106 Procedures).
- Agent
- IV alteplase + stent-retriever thrombectomy
- Dose
- 0.9 mg/kg (max 90 mg)
- Route
- IV (10% bolus, remainder over 60 min) then endovascular
- Co-interventions
- IV alteplase 0.9 mg/kg (max 90 mg) over 60 min with 10% bolus, started as early as possible; complete dose administered unless major contraindication; then Solitaire thrombectomy; balloon guide/distal aspiration encouraged; IA fibrinolytics prohibited.
Control = bridging alteplase before Solitaire thrombectomy (Fischer Lancet 2022 p.104,106).
Trial Design
Type
- European and Canadian randomized noninferiority trial
- Thrombectomy alone vs alteplase plus thrombectomy
- Direct presenters at endovascular centers
- Primary endpoint: mRS 0-2 at 90 days
Timeline
Enrolled 2017-2021
N
423
Enrollment
423 patients across European and Canadian comprehensive stroke centers. Open-label randomized non-inferiority trial. Enrolled 2018 to 2021. Stent-retriever technique per protocol. Published Lancet 2022.
ClinicalTrials.gov
NCT03192332Bedside Pearl
Give IV alteplase 0.9 mg/kg before thrombectomy in eligible anterior-circulation LVO. SWIFT DIRECT showed an 8-point absolute reduction in mRS 0-2 and 5-point lower TICI 2b-3 without alteplase, with the entire confidence interval favoring bridging therapy.