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TWIST

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

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Year of Publication: 2023

Authors: Melinda B Roaldsen MD, Agnethe Eltoft MD, Prof Tom Wilsgaard PhD, ..., Prof Gian Marco De Marchis MD

Journal: The Lancet Neurology

Citation: The Lancet Neurology, Volume 22, Issue 2, February 2023, Pages 117-126. https://doi.org/10.1016/S1474-4422(22)00484-7

Link: https://www.sciencedirect.com/science/ar...474442222004847

Clinical Question

To determine whether thrombolytic treatment with intravenous tenecteplase given within 4.5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT.

Bottom Line

In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. Current evidence does not support treatment with tenecteplase in this patient population.

Major Points

  • TWIST was a multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries.
  • 578 patients were enrolled and randomly assigned to a tenecteplase group or a control group. The trial was underpowered and did not reach its planned target of 600 patients.
  • The primary outcome of functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days, showed no significant difference between the groups (adjusted OR 1.18, 95% CI 0.88-1.58; p=0.27).
  • Mortality at 90 days was similar between the tenecteplase group (10%) and the control group (8%).
  • The risk of symptomatic intracranial haemorrhage and any intracranial haemorrhage was similar in both groups and consistent with findings from previous wake-up stroke trials.
  • The trial used non-contrast CT as a screening tool, which is widely available, but non-inferiority to selection using advanced imaging techniques could not be established.

Design

Study Type: Investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment.

Randomization: 1

Blinding: Endpoint assessors and research personnel were masked to treatment allocation. The trial was open-label for participants and treating clinicians.

Enrollment Period: June 12, 2017, to Sept 30, 2021.

Follow-up Duration: 90 days.

Centers: 77

Countries: Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, UK

Sample Size: 578

Analysis: Intention-to-treat population; ordinal logistic regression for primary outcome; binary logistic regression and Cox proportional hazard regression for secondary outcomes. Analyses were adjusted for age, baseline NIHSS score, and time from wake-up to randomisation.

Inclusion Criteria

  • Patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening.
  • Limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia.
  • A non-contrast CT examination of the head.
  • Ability to receive tenecteplase within 4.5 h of awakening.

Exclusion Criteria

  • Intracranial haemorrhage or infarct comprising hypoattenuation in more than a third of the middle cerebral artery territory on acute non-contrast CT.
  • A complete list of exclusion criteria is in the appendix.

Baseline Characteristics

CharacteristicControlActive
Age, years (mean/median)72.9 (11.6)/73.3 (65.8-82.0).72.7 (11.3)/73.9 (66.4-80.8).
Male168 (58%).164 (57%).
Atrial fibrillation31 (11%).55 (21%).
Premorbid mRS score 0191 (66%).188 (65%).
Median NIHSS score6 (5-10).6 (5-11).
Large vessel occlusion83/226 (37%).69/231 (30%).

Arms

FieldTenecteplase GroupControl
InterventionSingle intravenous bolus of tenecteplase 0.25 mg per kg of body weight (maximum 25 mg).No thrombolysis.
DurationSingle dose90 days follow-up

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Functional outcome assessed by the modified Rankin Scale (mRS) at 90 days.PrimaryMedian mRS score 2 (IQR 1-3).Median mRS score 2 (IQR 1-3).0.27.
Excellent functional outcome (mRS score of 0-1) at 90 days.Secondary111 (38%).130 (45%).1.34.null (95% CI 0.95-1.88).
Good functional outcome (mRS score of 0-2) at 90 days.Secondary173 (60%).177 (61%).1.07.null (95% CI 0.75-1.54).
Death within 90 days.Secondary23 (8%).28 (10%).1.29 (HR).0.37.
Symptomatic intracranial haemorrhage (SITS-MOST definition).Secondary3 (1%).6 (2%).2.17 (OR).0.28.
Any intracranial haemorrhage.Secondary30 (10%).33 (11%).1.14 (OR).0.64.
Death within 90 daysAdverse23 (8%).28 (10%).1.29 (HR).0.37.
Symptomatic intracranial haemorrhage (SITS-MOST definition)Adverse3 (1%).6 (2%).2.17 (OR).0.28.
Any intracranial haemorrhageAdverse30 (10%).33 (11%).1.14 (OR).0.64.

Subgroup Analysis

No treatment effect of tenecteplase was found in the subgroup of patients undergoing thrombectomy.

Based on: TWIST (The Lancet Neurology, 2023)

Authors: Melinda B Roaldsen MD, Agnethe Eltoft MD, Prof Tom Wilsgaard PhD, ..., Prof Gian Marco De Marchis MD

Citation: The Lancet Neurology, Volume 22, Issue 2, February 2023, Pages 117-126. https://doi.org/10.1016/S1474-4422(22)00484-7

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