← Back
NeuroTrials.ai
Neurology Clinical Trial Database

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

Share Share Copied! Compare

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.

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

Content summarized and formatted by NeuroTrials.ai.