TWIST Trial: Wake-Up Stroke Treated with Tenecteplase Selected by Non-Contrast CT
In wake-up stroke patients selected by non-contrast CT alone, does tenecteplase 0.25 mg/kg administered within 4.5 hours of awakening improve 90-day functional outcome compared with no thrombolysis?
Roaldsen MB, et al. (Lancet Neurol 2023) · doi:10.1016/S1474-4422(22)00484-7 · 578 patients
Population
Included
- Wake-up stroke or stroke with unwitnessed onset
- Treatable within 4.5 hours of awakening or recognition
- ASPECTS 4 or higher on non-contrast CT
- Age 18 to 80
- Aged 18 years or older
- Acute ischaemic stroke symptoms upon awakening that were not present before sleep
- Limb weakness
- A National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher, or aphasia
- Ability to receive tenecteplase within 4.5 hours of awakening
- A non-contrast CT examination of the head was a prerequisite for inclusion
Excluded
- Known time of symptom onset (wake-up criterion not met)
- Early ischemic changes beyond one-third MCA territory on NCCT
- Standard thrombolysis contraindications
- Intracranial haemorrhage on acute non-contrast CT
- Infarct comprising hypoattenuation in more than a third of the middle cerebral artery territory on acute non-contrast CT
- Standard contraindications to intravenous thrombolysis (complete list provided in the trial appendix)
Source: Roaldsen et al., Lancet Neurology 2023· Retrieved 2026-06-09
Primary Outcome — mRS Distribution at 90 Days
All randomized patients (578 patients, non-contrast CT selection)
Study Arms
- Agent
- Tenecteplase
- Dose
- 0.25 mg/kg (maximum 25 mg)
- Route
- Intravenous
- Frequency
- Single bolus
- Co-interventions
- Thrombectomy was allowed in both treatment groups.
Given within 4.5 hours of awakening. Bodyweight assessed per local routine practice.
- Agent
- No thrombolytic agent
- Co-interventions
- Thrombectomy was allowed in both treatment groups.
Patients did not receive tenecteplase or any other thrombolytic agent.
Trial Design
Type
- Investigator-initiated, multicenter, open-label randomized trial
- Wake-up stroke selected with non-contrast CT only
- Tenecteplase vs no thrombolysis
Timeline
Ten countries; June 2017 to September 2021
N
578
Enrollment
Randomized June 2017 to September 2021 across 10 countries. Investigator-initiated, multicenter, open-label trial. Wake-up stroke or unwitnessed onset; selected by NCCT alone (ASPECTS 4 or higher).
ClinicalTrials.gov
NCT03181360Bedside Pearl
TWIST is a negative trial for non-contrast CT-only selection of wake-up stroke for tenecteplase. Numerically more patients achieved mRS 0-1 with tenecteplase (45% vs 38%) but the ordinal shift was not significant. The take-home is imaging-specific: NCCT alone cannot reliably select patients likely to benefit. MRI DWI-FLAIR mismatch (WAKE-UP trial) or CTP penumbra remain the evidence-based selection strategies where available.
See also