SKIP Trial: Mechanical Thrombectomy Without vs With IV Thrombolysis
In Japanese patients with LVO stroke eligible for IV thrombolysis, does mechanical thrombectomy alone produce outcomes non-inferior to low-dose alteplase plus thrombectomy at 90 days?
Suzuki et al. (JAMA 2021) · doi:10.1001/jama.2020.23522 · 204 patients
Population
Included
- Age 18 or older
- Acute ischemic stroke with LVO of intracranial ICA, M1, M2, or basilar artery
- NIHSS 6 to 29
- Eligible for IV thrombolysis
- Treatment within 4.5 hours of last known well
- Pre-stroke mRS 0 or 1
- Age 18 to 85 years
- Acute ischemic stroke with internal carotid artery (ICA) or M1 occlusion evaluated by MRA or CTA
- Baseline ASPECTS 6 to 10, or DWI-ASPECTS 5 to 10
- Initial NIHSS score 6 or greater
- Functionally independent prior to stroke (modified Rankin Scale 0 to 2)
- Met Japanese-guideline criteria for treatment with lower-dose alteplase 0.6 mg/kg as intravenous thrombolysis within 4.5 hours from onset
Excluded
- Contraindication to IV alteplase
- Pre-stroke mRS greater than 1
- NIHSS less than 6 or greater than 29
- Presentation beyond 4.5 hours from last known well
- Detailed inclusion and exclusion criteria are provided in eBox 1 of Supplement 3 (not reproduced in the primary publication main text)
Source: Suzuki et al., JAMA 2021 (SKIP); reg. UMIN000021488· Retrieved 2026-06-08
Non-inferiority design: margin not met
SKIP tested whether direct EVT was acceptably close to low-dose alteplase (0.6 mg/kg) plus EVT (NI margin: OR lower CI greater than 0.75). Non-inferiority was not demonstrated: the lower CI bound (0.72) fell below the margin. Similar point estimates (59.4% vs 57.3%) do not establish equivalence.
Primary Outcome — mRS 0-2 at 90 Days (Non-inferiority)
LVO stroke within 4.5 h; Japanese low-dose alteplase (0.6 mg/kg) comparator
Small absolute difference — interpret with caution
mRS 0-2 at 90 Days
Study Arms
- Agent
- Mechanical thrombectomy (any device approved by the Japanese Ministry of Health, Labour and Welfare)
- Route
- Endovascular
- Co-interventions
- No intravenous alteplase. Balloon guide catheter selected as the guiding catheter; concomitant stenting/angioplasty of cervical and intracranial ICA lesions permitted without device restrictions; thrombectomy required to start within 30 minutes from randomization.
Direct-EVT arm, n=101. Suzuki JAMA 2021 p.245.
- Agent
- Alteplase
- Dose
- 0.6 mg/kg (low-dose; the only dose approved by the Japanese government)
- Route
- Intravenous
- Co-interventions
- Low-dose alteplase 0.6 mg/kg, followed by mechanical thrombectomy with any approved device; rt-PA infusion continued during thrombectomy; balloon guide catheter; thrombectomy required to start within 30 minutes from randomization.
Bridging arm, n=103. LOW-DOSE 0.6 mg/kg (NOT 0.9). Suzuki JAMA 2021 p.244-245.
Trial Design
Type
- Investigator-initiated Japanese noninferiority trial
- Mechanical thrombectomy alone vs low-dose alteplase plus thrombectomy
- LVO stroke without large ischemic core
- Open-label with randomized allocation
Timeline
Enrolled 2017-2019 across 23 networks
N
204
Enrollment
204 patients at 23 stroke networks across Japan. Open-label randomized non-inferiority trial. Enrolled 2017 to 2019. IV alteplase at Japanese approved dose of 0.6 mg/kg (not the 0.9 mg/kg dose used in European and American trials). Published JAMA 2021.
Bedside Pearl
Do not skip alteplase before thrombectomy on the basis of SKIP. Even with low-dose Japanese alteplase as comparator, non-inferiority failed. Give standard-dose IV thrombolysis in eligible LVO patients while activating the EVT pathway in parallel.