EXTEND-IA Trial: Perfusion-Selected EVT After Alteplase
In patients with anterior circulation LVO and CT-perfusion mismatch who had received IV alteplase, does adding Solitaire FR thrombectomy improve early reperfusion and neurological recovery compared with alteplase alone?
Campbell et al. (NEJM 2015) · doi:10.1056/NEJMoa1414792 · 70 patients
Population
Included
- Age 18 years or older
- Acute ischemic stroke with anterior circulation large-vessel occlusion (intracranial ICA or M1 or M2 MCA) on CTA or MRA
- IV alteplase started within 4.5 hours of symptom onset
- Endovascular thrombectomy achievable within 6 hours of onset
- CT perfusion or MRI perfusion-diffusion mismatch confirming salvageable tissue (ischemic core less than 70 mL, mismatch ratio greater than 1.2, mismatch volume greater than 10 mL)
- Pre-stroke functional independence (mRS 0 to 1)
Clinical inclusion
- Patients presenting with anterior circulation acute ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset
- Patient, family member or legally responsible person has given informed consent
- Patient's age is ≥18 years
- Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset
Imaging inclusion criteria: dual target
- Arterial occlusion on CTA or MRA of the ICA, M1 or M2
- Mismatch (using CT or MRI with a Tmax >6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume): (a) Mismatch ratio greater than 1.2, and (b) Absolute mismatch volume greater than 10 ml, and (c) Infarct core lesion volume less than 70 mL
Excluded
- Large established infarct core (greater than 70 mL)
- No perfusion mismatch (target mismatch profile not met)
- Severe pre-stroke disability
- Standard contraindications to endovascular treatment
- Posterior circulation stroke
- Intracranial haemorrhage (ICH) identified by CT or MRI
- Rapidly improving symptoms at the discretion of the investigator
- Pre-stroke mRS score of ≥2 (indicating previous disability)
- Inability to access the cerebral vasculature in the opinion of the neurointerventional team
- Contraindication to imaging with MR with contrast agents
- Participation in any investigational study in the previous 30 days
- Any terminal illness such that patient would not be expected to survive more than 1 year
- Any condition that, in the judgment of the investigator, could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study
- Pregnant women
- Previous stroke within last three months
- Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator
- Current use of oral anticoagulants and a prolonged prothrombin time (INR >1.6)
- Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated partial thromboplastin time exceeding the upper limit of the local laboratory normal range
- Use of glycoprotein IIb–IIIa inhibitors within the past 72 hours. Prior use of single or dual agent oral platelet inhibitors (clopidogrel and/or low-dose aspirin) is permitted
- Clinically significant hypoglycaemia
- Uncontrolled hypertension defined by a blood pressure >185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of "aggressive treatment" is left to the discretion of the responsible Investigator
- Hereditary or acquired haemorrhagic diathesis
- Gastrointestinal or urinary bleeding within the preceding 21 days
- Major surgery within the preceding 14 days which poses risk in the opinion of the investigator
- Exposure to a thrombolytic agent within the previous 72 hrs
Source: ClinicalTrials.gov NCT01492725· Retrieved 2026-06-08
Secondary outcome: mRS 0-2 at 90 days
Co-primary endpoint note: Both co-primary endpoints were met: reperfusion at 24 hours (100% vs 37%, P less than 0.001) and early neurological improvement at day 3 (80% vs 37%, P less than 0.001). The chart below shows the secondary functional outcome (mRS 0 to 2 at 90 days) for bedside context.
mRS 0-2 at 90 Days (Secondary Outcome)
Study Arms
- Agent
- Solitaire FR (Flow Restoration) retrievable stent (Covidien), deployed at the site of intracranial-vessel occlusion and removed under negative-pressure aspiration. If no lesion amenable to thrombectomy was found, the procedure was terminated.
- Route
- Endovascular
- Frequency
- Single procedure. Endovascular therapy initiated (groin puncture) within 6 h of onset and completed within 8 h; initiated at a median of 210 minutes after onset.
- Duration
- One-time procedure
- Co-interventions
- + IV alteplase 0.9 mg/kg as standard care, given to ALL patients in both groups (within 4.5 h of onset). Conscious sedation or general anesthesia at the neurointerventionist's discretion.
Device, 6 h/8 h targets, both-arm alteplase from Campbell NEJM 2015 p.1010-1011. 1:1 stratified by occlusion site. Solitaire FR only by protocol; does not generalize to other devices. Covidien supplied the device + unrestricted grant, no role in design/conduct. Source: NCT01492725.
- Agent
- IV alteplase alone, no endovascular therapy ('alteplase-only group')
- Route
- IV (medical management)
- Co-interventions
- IV alteplase 0.9 mg/kg as standard care, given to ALL patients in both groups (within 4.5 h of onset). No protocol-mandated endovascular therapy.
Control = continue alteplase alone with no further therapy (Campbell NEJM 2015 p.1011). Both arms received identical IV alteplase; the trial isolates the added effect of Solitaire FR thrombectomy. Control-arm BP/glucose/antithrombotic targets appendix-deferred. Source: NCT01492725.
Trial Design
Type
- Randomized trial after IV alteplase
- Perfusion-imaging selection for salvageable tissue
- Solitaire FR thrombectomy vs alteplase alone
- Occlusion in ICA or MCA with core <70 mL
Timeline
Stopped early for efficacy
N
70
Enrollment
Investigator-initiated multicenter RCT enrolling 70 patients in Australia and New Zealand between August 2012 and October 2014 (Campbell NEJM 2015). Stopped early for efficacy after 70 of 100 planned patients.
ClinicalTrials.gov
NCT01492725Bedside Pearl
When CT perfusion shows a small core and a large penumbra in an LVO patient who has just received alteplase, EXTEND-IA supports moving immediately to thrombectomy. The reperfusion gap (100% vs 37%) is the mechanistic anchor for the functional benefit; the mRS gain (71% vs 40%) is the bedside number to quote.
See also