| Trial name or title |
Tenecteplase in Wake‐up Ischaemic Stroke Trial (TWIST) |
| Methods |
PROBE; prospective, randomised, open, blinded‐endpoint |
| Participants |
500 participants
Inclusion criteria
Stroke symptoms on awakening that were not present before sleep Clinical diagnosis of stroke with limb weakness with an NIHSS score > 5, or dysphasia Treatment with tenecteplase is possible within 4.5 hours of awakening Written consent from the patient, non‐written consent from the patient (witnessed by non‐participating healthcare personnel), or written consent from the nearest family member
Exclusion criteria
Age < 18 years NIHSS score > 25 or NIHSS consciousness score > 2, or seizures during stroke onset Findings on plain CT that indicate that the patient is unlikely to benefit from treatment: infarction comprising more than > 1/3 of the middle cerebral artery territory on plain CT or CT perfusion Intracranial haemorrhage, structural brain lesions that can mimic stroke (e.g. cerebral tumour) Patient will be treated with intra‐arterial interventions for proximal cerebral artery occlusion Active internal bleeding of high risk of bleeding, e.g. major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non‐compressible site within the previous 7 days. Any known defect in coagulation, e.g. current use of vitamin K antagonist with an INR > 1.7 or prothrombin time > 15 seconds, or use of direct thrombin inhibitors or direct factor Xa inhibitors during the last 24 hours (unless reversal of effect can be achieved by agents such as idarucizumab or andexanet) or with elevated sensitive laboratory tests (such as aPTT, INR, platelet count, ecarin clotting time, thrombin time, or appropriate factor Xa activity assays), or heparins during the last 24 hours or with an elevated aPTT greater than the upper limit of normal, known defect of clotting or platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents may be included), ischaemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury, or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation, or aneurysm Contraindications to tenecteplase, e.g. acute bacterial endocarditis or pericarditis; acute pancreatitis; severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension; active hepatitis; systemic cancer with increased bleeding risk; haemostatic defect including secondary to severe hepatic, renal disease; organ biopsy; prolonged cardiopulmonary resuscitation > 2 min (within 2 weeks) Persistent blood pressure elevation (systolic ≥ 185 mmHg or diastolic ≥ 110 mmHg), despite blood pressure‐lowering treatment Blood glucose < 2.7 or > 20.0 mmol/L (use of finger‐stick measurement devices is acceptable) Pregnancy, positive pregnancy test, childbirth during last 10 days, or breastfeeding. In any woman of childbearing potential, a pregnancy test must be performed and the result assessed before trial entry Other serious or life‐threatening disease before the stroke: severe mental or physical disability (e.g. Mini Mental Status score < 20 or mRS score ≥ 3), or life expectancy less than 12 months Patient unavailable for follow‐up (e.g. no fixed address)
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| Interventions |
Tenecteplase + best standard treatment or no tenecteplase + best standard treatment Tenecteplase is given as a 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), administered as a bolus over approximately 10 seconds |
| Outcomes |
Primary outcome measures
Secondary outcome measures
Symptomatic intracranial haemorrhage during the first 7 days. Symptoms (neurological deterioration, new headache, new acute hypertension, new nausea or vomiting, or sudden decrease in conscious level). Intracranial haemorrhage on brain MRI or CT. Asymptomatic intracranial haemorrhage during the first 7 days. Intracranial haemorrhage on brain MRI or CT without: neurological deterioration, new headache, new acute hypertension, new nausea or vomiting, or sudden decrease in consciousness level Recurrent ischaemic stroke during the first 7 days. Neurological deterioration (increase of ≥ 2 on the NIHSS, after exclusion of other causes for neurological deterioration) occurring after 72 hours will be considered as a recurrent stroke. A recurrent stroke will be classified as ischaemic if imaging has excluded haemorrhage Death from all causes (time frame: first 7 days). Death will be classified according to cause: initial stroke, recurrent stroke, myocardial infarction, pneumonia, or other Death from all causes (time frame: 3 months). Death will be classified according to cause: initial stroke, recurrent stroke, myocardial infarction, pneumonia, or other Barthel Index score (time frame: 3 months). Ordinal scale for measuring performance in activities of daily living EuroQol Score (EQ‐5D) (time frame: 3 months). Measure of health‐related quality of life Mini Mental State Examination (time frame: 3 months). 30‐point questionnaire for measurement of cognitive impairment Health‐economic variables. Costs related to length of hospital stay, nursing home care after discharge, rehospitalisations during first 3 months Functional outcome at 3 months. Functional outcome assessed by dichotomised mRS score; values 0 to 1 vs 2 to 6
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| Starting date |
June 2017 |
| Contact information |
Trial Manager: Melinda B Roaldsen; e‐mail: melinda.b.roaldsen@uit.no or twist@uit.no |
| Notes |
ClinicalTrials.gov identifier NCT03181360
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