Ischemic Stroke, Acute
Conditions
Keywords
rhTNK-tPA, rt-PA, Ischemic stroke, phase III trial, basilar artery occlusion
Brief summary
The trial is a multicentre, prospective, open-label, blinded endpoint (PROBE), phase 3, randomized controlled design. Patients with acute ischemic stroke due to basilar artery occlusion presenting within 24 hours will be randomized 1:1 to intravenous tenecteplase (0.25mg/kg, maximum 25mg) ± thrombectomy or 'best practice'which may be alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion.
Detailed description
The study will be a multicentre, prospective, open-label, blinded endpoint (PROBE), randomized controlled trial (2 arm with 1:1 randomization) in patients with acute ischemic stroke due to basilar artery occlusion presenting to hospital within 24 hours of symptom onset. Patients will be required to have complete or near-complete occlusion of the basilar artery on baseline computed tomography angiography (CTA)/magnetic resonance angiography (MRA), defined as 'potentially retrievable' thrombus in the basilar artery. Thrombectomy is permitted within 24 hours as part of standard care but is not mandatory. Patients will be randomized to treatment with either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg within 4.5 hours from stroke onset) or intravenous tenecteplase (0.25mg/kg, maximum 25mg). Time of onset of symptoms is defined as described by the patient or witness; if unknown, it is considered to be the last time the patient was seen well. In patients presenting with mild (e.g. vertigo, dizziness, headache, diplopia, dysarthria) stuttering symptoms followed by sudden onset of clinical deterioration with decrease in conscious state or moderate to severe motor deficits, the time of deterioration in clinical state is taken as the estimated time of basilar artery occlusion.
Interventions
DRUGTenecteplase
Intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds) within 24 hours ± thrombectomy at treating clinician's discretion
DRUGBest Practice (which may include intravenous Alteplase)
Intravenous alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18. 2. Patients presenting with posterior circulation ischemic stroke symptoms due to near-complete or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well. 3. Presence of a basilar artery occlusion, proven by CT Angiography or MR Angiography. Basilar artery occlusion will be defined as 'potentially retrievable' occlusion at the basilar artery. This can be a near or complete occlusion. 4. Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week). 5. Local legal requirements for consent have been satisfied.
Exclusion criteria
1. Intracerebral haemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging. 2. Posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) \<6 on non-contrast CT (NCCT) or CTA-source images or MRI diffusion weighted imaging (DWI). 3. Significant cerebellar mass effect or acute hydrocephalus. 4. Established frank hypodensity on non-contrast CT indicating subacute infarction. 5. Bilateral extensive brainstem ischemia. 6. Pre-stroke mRS of ≥4 (indicating moderate to severe previous disability). 7. Other standard contraindications to intravenous thrombolysis. 8. Contraindication to imaging with contrast agents. 9. Clinically evident pregnant women. 10. Vessel imaging showing both anterior and posterior circulation large vessel occlusion. 11. Current participation in another research drug treatment protocol. 12. Known terminal illness such that the patients would not be expected to survive a year. 13. Planned withdrawal of care or comfort care measures. 14. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale (mRS) 0-1 or return to baseline mRS | 3 months | The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale (mRS) 0-3 or return to baseline mRS | 3 months | Proportion of patients with Modified Rankin Scale (mRS) 0-3 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death). |
| Ordinal analysis of the Modified Rankin Scale (mRS) | 3 months | Ordinal analysis of the Modified Rankin Scale (mRS), merging category 5-6, at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death). |
| Early neurological improvement | 72 hours | Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour National Institutes of Health Stroke Scale \[NIHSS\] score of ≥8 or 72 hour NIHSS 0-1). |
| Successful reperfusion | initial DSA run prior to thrombectomy | Proportion of patients with complete occlusion at baseline who achieve expanded Thrombolysis In Cerebral Infarction score (eTICI) 2b/3 on initial digital subtraction angiography (DSA) run prior to thrombectomy. |
| Modified Rankin Scale (mRS) 0-2 or return to baseline mRS | 3 months | Proportion of patients with Modified Rankin Scale (mRS) 0-2 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death). |
| All-cause mortality | 90 days | All-cause mortality within 90 days. |
| Severe disability or death | 90 days | Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death). Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death). |
| Clinical deterioration | 24 hours | Proportion of patients with partially occlusive thrombus at baseline who have clinical deterioration within 24 hours leading to further treatment (e.g. endovascular thrombectomy). |
| Vessel recanalization | 24+/-6 hours | Vessel recanalization rate evaluated by CT or MR angiography within 24+/-6 hours (if performed). |
| Symptomatic intracranial hemorrhage (sICH) | 36 hours | Proportion of patients with symptomatic intracranial hemorrhage (sICH) defined as local or remote parenchymal hemorrhage type 2 (PH2) on the 22-36 hours post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 hours, or leading to death. |
Countries
China
Outcome results
None listed