ORIGINAL Trial: Tenecteplase vs Alteplase for Acute Ischemic Stroke (0–4.5 Hours)
In Chinese patients with acute ischemic stroke within 4.5 hours of onset, is intravenous tenecteplase 0.25 mg/kg noninferior to intravenous alteplase 0.9 mg/kg for mRS 0–1 at 90 days?
Meng X et al. (JAMA 2024) · doi:10.1001/jama.2024.14721 · 1,465 patients
Population
Included
- Age ≥18
- Acute ischemic stroke eligible for IV thrombolysis within 4.5h
- NIHSS 1–25 (with measurable motor deficit if NIHSS <4)
- Noncontrast CT to exclude ICH
- Chinese adults (aged 18 years or older)
- Acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of 1 to 25
- Measurable neurologic deficit
- Symptomatic for at least 30 minutes without significant improvement
- Able to receive thrombolytic therapy within 4.5 hours of symptom onset
- Individuals with an NIHSS score of less than 4 were required to have a measurable deficit in motor function score for the arms or legs of at least 1
- Individuals in whom endovascular thrombectomy was planned were eligible
- Noncontrast computed tomography was used at screening to exclude patients presenting with intracranial hemorrhage
Excluded
- Standard IV thrombolysis contraindications
- Treatment >4.5h from symptom onset
- Pre-stroke significant disability
- Intracranial hemorrhage on screening noncontrast computed tomography
- Symptomatic for less than 30 minutes or with significant improvement before treatment
- Unable to initiate thrombolytic therapy within 4.5 hours of symptom onset
- NIHSS score outside the 1 to 25 range
- Standard contraindications to intravenous thrombolysis (full exclusion list provided in the trial supplement)
Source: Meng et al., JAMA 2024· Retrieved 2026-06-09
Primary Outcome — Non-inferiority
Non-inferiority design: The trial asks whether TNK is at least as good as alteplase within a pre-specified margin (RR ≥0.937), not whether TNK is better. NI margin met: RR 1.03 (95% CI 0.97–1.09). Do not derive an NNT from this trial — the design does not establish a superiority effect size.
Small absolute difference — interpret with caution
mRS 0–1 at 90 Days
Study Arms
- Agent
- Tenecteplase
- Dose
- 0.25 mg/kg (maximum 25 mg)
- Route
- Intravenous
- Frequency
- Single bolus over 5 to 10 seconds
Administered within 4.5 hours of ischemic stroke symptom onset.
- Agent
- Alteplase
- Dose
- 0.9 mg/kg (maximum 90 mg)
- Route
- Intravenous
- Frequency
- 10% as an initial bolus, remainder as an infusion over 1 hour
Active comparator. Administered within 4.5 hours of ischemic stroke symptom onset.
Safety
Symptomatic ICH (ECASS III definition)
1.2%
1.2%
Identical safety: 1.2% in both arms (RR 1.01, 95% CI 0.37–2.70). TNK 0.25 mg/kg does not increase ICH risk vs alteplase 0.9 mg/kg.
90-day mortality
4.6%
5.8%
4.6% TNK vs 5.8% alteplase (RR 0.80, 95% CI 0.51–1.23). Numerically lower with TNK but not statistically significant.
Trial Design
Type
- Multicenter randomized open-label blinded-endpoint (PROBE) trial
- Active-controlled noninferiority design
- 1:1 allocation (Tenecteplase 0.25 mg/kg vs Alteplase 0.9 mg/kg)
- 55 neurology clinics and stroke centers in China
Timeline
Enrolled July 2021 – July 2023
N
1,465
Enrollment
1,465 patients (732 TNK / 733 alteplase) at 55 stroke centers in China. Enrolled July 2021 – July 2023. Published JAMA 2024;332(17):1437–1445.
ClinicalTrials.gov
NCT04915729Bedside Pearl
For acute ischemic stroke within 4.5 hours, tenecteplase 0.25 mg/kg (single IV bolus) is noninferior to alteplase 0.9 mg/kg (1-hour infusion). AHA/ASA 2026 §4.6.2: either agent is recommended (COR 1). Single-bolus TNK simplifies drip-and-ship workflow.
See also