ATTEST-2 Trial: Tenecteplase vs Alteplase Within 4.5 Hours
In acute ischemic stroke patients eligible for IV thrombolysis within 4.5 hours, is tenecteplase 0.25 mg/kg noninferior to alteplase 0.9 mg/kg for 90-day functional outcome?
Muir KW, et al. (Lancet Neurol 2024) · doi:10.1016/S1474-4422(24)00377-6 · 1777 patients
Population
Included
- Acute ischemic stroke eligible for IV thrombolysis
- Within 4.5 hours of onset
- Age 18 or older
- NIHSS 4 or higher, or disabling deficit
- Previously independent (estimated pre-stroke modified Rankin Scale score of 0 to 2)
- Adults aged 18 years or older
- Acute ischaemic stroke presenting within 4.5 h of last known well
- Eligible for intravenous thrombolysis according to national guidelines
Excluded
- Standard thrombolysis contraindications
- Prior thrombolysis within 3 months
- Significant anticoagulation
- Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (for example a CNS neoplasm) on pre-treatment brain imaging
- Stroke within the previous 14 days
- Thrombolytic therapy within the past 14 days
- Hypodensity on pre-treatment CT scan consistent with recent cerebral ischaemia other than the presenting event
- Systolic blood pressure of more than 185 mm Hg or diastolic blood pressure of more than 110 mm Hg, or intravenous pharmacotherapy (repeated bolus or continuous infusion) necessary to reduce blood pressure to these limits
- Clinical history suggestive of subarachnoid haemorrhage
- Medical conditions representing a high risk of haemorrhage
- Hypoglycaemia (less than 2.8 mmol/L) or hyperglycaemia (more than 22.2 mmol/L)
- Seizure at the onset of symptoms, unless brain imaging identified positive evidence of acute symptomatic brain ischaemia
- Pregnancy
- Inadequate haemostasis, including an International Normalised Ratio of more than 1.3 if on warfarin less than 12 h from the administration of any direct oral anticoagulant
- Use of low molecular weight heparin within 48 h
- Any major medical condition likely to limit survival to day 90
- Anticipated unavailability for day 90 follow-up
Source: Muir KW, et al., Lancet Neurol 2024· Retrieved 2026-06-09
Primary Outcome — mRS Distribution at 90 Days
All treated patients (1777 patients, 39 UK centres)
Study Arms
- Agent
- Tenecteplase
- Dose
- 0.25 mg/kg (max 25 mg)
- Route
- IV
- Frequency
- Single bolus
- Duration
- One-time
- Co-interventions
- Endovascular thrombectomy permitted where clinically indicated; local protocols for blood pressure management followed
- Agent
- Alteplase
- Dose
- 0.9 mg/kg (max 90 mg)
- Route
- IV
- Frequency
- 10% as bolus, then 90% over a 1-h infusion
- Duration
- 60 minutes
- Co-interventions
- Endovascular thrombectomy permitted where clinically indicated; local protocols for blood pressure management followed
Trial Design
Type
- Prospective, randomized, parallel-group, open-label trial with masked endpoints
- Tenecteplase 0.25 mg/kg vs alteplase 0.9 mg/kg
- 39 UK stroke centres
Timeline
United Kingdom; January 2017 to May 2023
N
1777
Enrollment
Randomized January 2017 to May 2023 at 39 UK stroke centres. Open-label, masked-endpoint (PROBE design). Primary analysis was noninferiority in the treated population.
ClinicalTrials.gov
NCT02814409Bedside Pearl
ATTEST-2 is the largest UK trial confirming that tenecteplase 0.25 mg/kg is noninferior to alteplase 0.9 mg/kg for standard-window IVT (NI p<0.0001). The single-bolus dosing advantage is now validated across three major trials (AcT, TRACE-2, ATTEST-2). Symptomatic ICH and mortality were identical in both arms. For centers transitioning to tenecteplase, ATTEST-2 provides reassurance that this is a direct substitution, not a clinical downgrade.