Ischemic Stroke
Conditions
Brief summary
The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?
Interventions
DRUGIntravenous recombinant tissue plasminogen activator (rtPA) Alteplase
IV Alteplase 0.9mg/kg (max 90mg) bolus + 1h infusion
IV Tenecteplase 0.25mg/kg (max 25mg) single bolus
Sponsors
University of Glasgow
University of Edinburgh
Oxford University Hospitals NHS Trust
NHS Greater Glasgow and Clyde
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eligible for intravenous thrombolysis. * Male or non-pregnant female ≥18 years of age. * \<4.5h after symptom onset. * Consent of patient or legal representative. * Independent prior to the stroke (estimated modified Rankin Scale 0-2).
Exclusion criteria
* Eligible for intravenous thrombolysis: Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg Central Nervous System neoplasm) on pre-treatment computerised tomography (CT) scan; Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment computerised tomography (CT) scan consistent with recent cerebral ischaemia other than the presenting event; Systolic blood pressure more than 185 or diastolic blood pressure more than 110 mmHg, or aggressive management (intravenous pharmacotherapy) necessary to reduce blood pressure to these limits; Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on computerised tomography (CT) scan; High risk of haemorrhage, including major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days; Arterial puncture at a non-compressible site within the previous 7 days; Prolonged cardiopulmonary resuscitation (\> 2 minutes) within the previous 14 days; Acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; Active peptic ulceration; Known history of haemorrhagic stroke; Known defect of clotting or platelet function (other than antiplatelet therapy); Hypo- or hyperglycaemia (blood glucose \<2 mmol/l or \>18 mmol/l) sufficient to account for neurological symptoms; Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain computerised tomography (CT) scan, computerised tomography angiography (CTA) scan confirmed arterial occlusion); Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation); Inadequate haemostasis: Taking warfarin and international normalised ratio (INR) \>1.3, Taking a Direct Oral Anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) unless known to be \>12 hours since last dose and with normal coagulation assays, Low molecular weight heparin (at doses other than prophylaxis of venous thromboembolism) administered within the preceding 48 hours, Unfractionated heparin administered within the previous 48 hours and activated partial thromboplastin time (APTT) is prolonged. * Any major medical condition likely to limit survival to day 90. * Unavailable for day 90 follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| modified Rankin Scale | Day 90 (+/- 7) | modified Rankin Scale (mRS) at day 90, determined by the Rankin Focused Assessment (RFA) method using centralised telephone interview, analysed by ordinal distribution (shift) analysis of the scores in intervention and control groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Full neurological recovery (modified Rankin Scale 0-1 versus 2-6). | Day 90 (+/- 7) | Full neurological recovery (modified Rankin Scale 0-1 versus 2-6). |
| Independent recovery (modified Rankin Scale score 0-2 versus 3-6). | Day 90 (+/- 7) | Independent recovery (modified Rankin Scale score 0-2 versus 3-6). |
| Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s). | 24 hours | Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s). |
| Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D) | Day 90 (+/- 7) | Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D) |
| Barthel Index score | Day 90 (+/- 7) | Barthel Index score |
| Need for thrombectomy | 24 hours | Need for thrombectomy |
Other
| Measure | Time frame | Description |
|---|---|---|
| Imaging scan up to 36 hours, combined with a neurological deterioration NIHSS≥4 points from baseline (or lowest NIHSS value baseline-24 h), or leading to death (Safe Implementation of Thrombolysis in Stroke-Monitoring study definition). | 36 hours | Imaging scan up to 36 hours, combined with a neurological deterioration NIHSS≥4 points from baseline (or lowest NIHSS value baseline-24 h), or leading to death (Safe Implementation of Thrombolysis in Stroke-Monitoring study definition). |
| Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke Study) ECASS-2 and ECASS-3 definitions. | up to day 90 | Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke |
| Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised tomography (CT) scan up to 36 hours after treatment. | 36 hours | Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised |
| Intracranial haemorrhage | 22-36 hours | Any intracranial haemorrhage on 22-36 hours computerised tomography (CT) scan |
| Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of ≥20mg/l in the 36h after treatment). | 36 hours | Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of ≥20mg/l in the 36h after treatment). |
| Mortality | Day 90 (+/- 7) | Mortality |
Countries
United Kingdom
Outcome results
None listed