Tenecteplase in Wake-up Ischaemic Stroke Trial "TWIST"

Recruiting

Phase 3 Results N/A

Trial Description

Stroke is a leading causes of death and disability. At least 20% of strokes occur during sleep, so- called 'wake up stroke'. Thrombolysis with the clot-busting drug alteplase is effective for acute ischaemic stroke, provided that it is given within 4.5 hours of symptom onset. Patients with wake-up stroke are currently ineligible for clot-busting therapy. Previous studies indicate that many wake-up strokes occur just before awakening.
In this study, patients with wake-up stroke will be randomized to thrombolysis with tenecteplase and best standard treatment or to best standard treatment without thrombolysis. Tenecteplase has several potential advantages over alteplase, including very rapid action and that it can be given as a single injection. Prior to thrombolysis, a brain scan must be done to exclude bleeding or significant brain damage as a result from the stroke. We will use a CT scan to inform this decision. CT is used as a routine examination in all stroke patients. Other studies testing clot-busting treatment in wake-up stroke are using alteplase and more complex brain scans, which are not routinely available in the emergency situation in all hospitals.

Detailed Description

Background:
One in five strokes occur during sleep, but patients with "wake-up" stroke are not given thrombolytic therapy because time of stroke onset is unknown. On-going trials are testing alteplase, and use MRI techniques for selection of patients. Tenecteplase has many pharmacological advantages over alteplase: greater fibrin specificity, very rapid action, longer half-life, and single bolus administration. In addition, patient selection based on MRI findings risks excluding many patients that might otherwise benefit. TWIST will test tenecteplase and will not use MRI techniques for selection of patients. Plain CT and CT angiography (if possible) will be performed before randomisation, and CT perfusion will be performed at selected centres, as part of a sub-study.
Study design: TWIST is an international, multi-centre, randomised, open-label, blinded-endpoint trial of tenecteplase for acute ischaemic 'wake-up' stroke.
Study questions:
1. Can tenecteplase given <4.5 hours of awakening improve functional outcome at 3 months?
2. Can findings on cerebral plain CT and CT angiography (and CT perfusion, at selected centres) identify patients who benefit from such treatment, compared to other patients?
Patients eligible for treatment who are able to receive tenecteplase within 4.5 hours of waking, will be randomly allocated to treatment with tenecteplase in addition to best standard treatment, versus best standard treatment.
Randomisation and treatment: Central randomisation (over the internet) to tenecteplase 0.25 mg/mg i.v. (maximum dose 25 mg) plus best medical treatment vs. best medical treatment alone.
Imaging: All patients will undergo CT and CT angiography (CTA, if possible) before randomisation and on day 2. CT perfusion (CTP) will be performed at selected centres, as part of a sub-study.
Follow-up and primary effect variable: Centralised follow-up via telephone or mail at 3 months. The primary effect variable is functional outcome (modified Rankin Scale score).
Study size and centers: 500 patients from centers in Norway, Sweden, Denmark, Finland, Estonia, Lithuania, United Kingdom and Switzerland.

Conditions

Interventions

  • Tenecteplase (TNKase)Drug
    Other Names: Metalyse
    Intervention Desc: Single dose intravenous injection of recombinant fibrin-specific tissue plasminogen activator (tenecteplase) 0.25 mg (200 IU) per kg body weight up to a maximum of 25 mg (5000 IU), given as a bolus over approx. 10 seconds.
    ARM 1: Kind: Experimental
    Label: Tenecteplase
    Description: Tenecteplase + Best standard treatment
  • Control Device
    Intervention Desc: Best standard treatment
    ARM 1: Kind: Experimental
    Label: Control
    Description: No tenecteplase + Best standard treatment

Outcomes

Type Measure Time Frame Safety Issue
Primary Functional outcome at 3 months. 3 months
Secondary Symptomatic intracranial haemorrhage during the first 7 days. First 7 days
Secondary Asymptomatic intracranial haemorrhage during the first 7 days. First 7 days
Secondary Recurrent ischaemic stroke during the first 7 days First 7 days
Secondary Death from all cause First 7 days
Secondary Barthel Index score 3 months
Secondary EuroCol Score 3 months
Secondary Mini Mental State Examination 3 months
Secondary Health-economic variables 3 months
Secondary Functional outcome at 3 months 3 months
Secondary EuroQol Score (EQ-5D) 3 months

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