Historical Reference Page
This is a historical reference page. This trial preceded the modern evidence base. It is presented as a predecessor reference. See ESCAPE (2015) for the modern successor trial that established EVT as standard of care.
IMS-III Trial: Endovascular Therapy After IV Alteplase for Acute Ischemic Stroke
In patients with moderate-to-severe acute ischemic stroke (NIHSS 8 or greater) treated with IV alteplase within 3 hours, does adding endovascular therapy improve 90-day functional independence compared with IV alteplase alone?
Broderick et al. (NEJM 2013) · doi:10.1056/NEJMoa1214300 · 656 patients
Population
Included
- Age 18 to 82 years
- Acute ischemic stroke with onset within 3 hours
- IV alteplase initiated (0.9 mg/kg standard dose)
- NIHSS 8 to 29 (moderate to severe stroke)
- CT or MRI excluding hemorrhage
Age and time window
- 18 to 82 years of age
- Receipt of intravenous t-PA within 3 hours after symptom onset
Neurologic severity
- Moderate-to-severe neurologic deficit, defined as an NIHSS score of 10 or higher
- After approval of amendment 3, an NIHSS score of 8 to 9 with CT angiographic evidence of an occlusion of the first segment of the middle cerebral artery (M1), internal carotid artery, or basilar artery
Consent
- Written informed consent obtained from the patient or a legal representative
Excluded
- Rapidly improving neurological status (NIHSS below 8 at randomization)
- Intracranial hemorrhage on baseline imaging
- Major contraindication to alteplase or contrast material
- Endovascular treatment not achievable within 7 hours of onset
- Severe pre-stroke disability
Per protocol
- Detailed inclusion and exclusion criteria are provided in Table 1 in the Supplementary Appendix; the full exclusion list is not reproduced in the main publication text
Source: Broderick et al., NEJM 2013· Retrieved 2026-06-09
Primary Outcome — mRS 0-2 at 90 Days
656 patients; endovascular therapy plus IV alteplase vs IV alteplase alone
In 656 patients with moderate-to-severe ischemic stroke (NIHSS 8 or greater) who received IV alteplase within 3 hours, adding endovascular therapy did not improve functional independence at 90 days. mRS 0-2 was achieved in 40.8% of the endovascular group versus 38.7% in the IV-only group (adjusted RR 1.05, 95% CI 0.83 to 1.30), a difference that was not statistically significant. The trial was stopped early at a planned interim analysis for futility; the data safety monitoring board concluded the primary endpoint was very unlikely to be met with full enrollment.
Visualization not shown for predecessor reference pages. See source paper for figures.
Trial Design
IMS-III enrolled patients who received IV alteplase (0.9 mg/kg standard dose) within 3 hours of stroke onset and had an NIHSS of 8 or greater. Patients were randomized within 40 minutes of alteplase infusion start to continue IV alteplase alone or proceed to endovascular therapy. The endovascular arm used intra-arterial tPA and, in many cases, coil-based mechanical devices (MERCI retriever, early Penumbra system). Critically, CTA or MRA confirmation of large-vessel occlusion was not required; a substantial proportion of enrolled patients likely had no retrievable thrombus, diluting any treatment effect.
Safety
Symptomatic intracranial hemorrhage was 6.2% endovascular versus 5.9% IV-only (p=0.83). Mortality at 90 days was 19.1% versus 21.6% (p=0.33). No significant safety difference between arms.