Acute Ischemic Stroke, Large Vessel Occlusion, Transportation of Patients
Conditions
Keywords
interhospital transfer, acute ischemic stroke, anterior circulation large vessel occlusion
Brief summary
This study will address the efficacy and safety of Tenecteplase administered in non-endovascular capable center (nECC) in patients with acute ischemic stroke (AIS) caused by anterior circulation large vessel occlusion (acLVO) who present in the 4.5- to 24-hour time window before interhospital transfer to an endovascular capable center (ECC) for endovascular treatment (EVT). * Primary objective: To evaluate the efficacy and safety of Tenecteplase administration at a nECC before EVT transfer compared with standard of care * Secondary objective: To evaluate the impact of time from needle-to-arterial puncture on clinical outcomes Patients who meet inclusion criteria will be randomized to Tenecteplase (0.25mg/kg, maximum 25mg) before transfer or standard of care. A single bolus dose should be injected over 5 seconds.
Interventions
Tenecteplase at a nECC before EVT transfer
Sponsors
Xuanwu Hospital, Beijing
Boehringer Ingelheim (China) Investment Co., Ltd
Jeffrey Saver
Maarten Lansberg
Thanh N. Nguyen
Pierre Seners
Jens Fiehler
Raul G. Nogueira
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Each ECC/nECC will designate one or more physician(s) to perform the follow-up evaluation at 24 (±12) hours, 7 (±2) days or discharge if earlier who cannot be involved in care of the subjects and must remain blinded to treatment assignment. Blinded assessors must undergo a standardized training and competency validation before delegated by the site principal investigator (PI). Assessment of the primary outcome on the mRS at 90 (±7) days will be performed by a qualified neurologist via structured telephone interview, blinded to both the allocated and actually received treatment. All telephone interviews will be recorded by audio and formed into follow-up reports, which will then be centrally assessed by two experienced and certified physicians. For cases with disagreement between the two assessors, decisions are made by the third experienced neurologist.
Intervention model description
This is a phase Ⅲ, multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of 18 years or older; * AIS symptom onset to treatment initiation within 4.5 to 24 hours, stroke onset is defined as the time the patient was last known to be well (including wake-up stroke and unwitnessed stroke); * Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the internal carotid artery (ICA), M1 or proximal M2 vessels; * Functionally independent (mRS 0-2) prior to stroke onset; * Baseline National Institute of Health Stroke Scale (NIHSS) of 6-25; * Intended to transfer to ECCs for EVT (patient transfer), or intended to transfer a neurointerventionalist from the ECC for EVT (physician transfer); * Written informed consent from patients or legally authorized representatives; * Neuroimaging: large vessel occlusion (ICA, M1, proximal M2) by MRA or CTA AND the target mismatch profile on computed tomography perfusion (CTP) or magnetic resonance perfusion (MRP), defined as an ischemic core volume \<70mL, mismatch volume ≥15mL and mismatch ratio ≥1.8; Alternative neuroimaging (if CTP or MRP is technically inadequate or unavailable): An Alberta Stroke Program Early CT Score (ASPECTS) score ≥7 on NCCT or MRI scan;
Exclusion criteria
* Known hypersensitivity or allergy to any ingredients of Tenecteplase; * Intended to receive IVT as standard-of-care therapy; * Rapidly improving symptoms with NIHSS score \<6 before randomization; * Any contra-indication for IVT except for the time criterion; * Known hereditary or acquired hemorrhagic diathesis; * Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, INR \>1.7 or prothrombin time \>15s; if use of any direct oral anticoagulant within the last 48 hours; if on any full dose heparin/heparinoid within the last 24 hours; * Ischemic stroke or myocardial infarction in previous 3 months * Previous intracranial hemorrhage, active internal bleeding (gastrointestinal or urinary tract hemorrhage) in previous 3 months; * Severe, uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg); * Other serious, advanced or terminal illness with life expectancy less than 6 months; * Baseline blood glucose \<50mg/dl or \>400mg/dl; * Contraindication to imaging with contrast agents; * Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA or MRA (e.g. bilateral MCA occlusions, or an MCA and a basilar artery occlusion); * Extensive early ischemic change on non-contrast CT or MRI-DWI estimated to be \>1/3 MCA territory, or significant hypodensity outside the Tmax\>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria); any CT or MRI findings indicative of a high risk of sICH related to potential intravenous tenecteplase treatment in the judgement of the investigator; * Evidence of intracranial tumor (mass effect), acute intracranial hemorrhage, or arteriovenous malformation; * Current participation in another investigational drug or device study; * Suspected endocarditis; * 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 |
|---|---|---|
| Level of disability (ordinal mRS score) | at 90 (±7) days | the ordinal score on the modified Rankin scale; The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Excellent outcome | at 90 (±7) days | mRS of 0-1 vs. 2-6 |
| Functional independence | at 90 (±7) days | mRS of 0-2 vs. 3-6 |
| Ambulatory and self-care capable | at 90 (±7) days | mRS of 0-3 vs. 4-6 |
| Health-related quality of life | at 90 (±7) days | Score on the EuroQol Group 5-Dimension 5-Level \[EQ-5D-5L\] questionnaire; range, -0.39 to 1, with higher scores indicating better quality of life) |
| Incidence of arterial recanalization | Day 1 | Arterial imaging performed at ECC arrival, either CTA/MRA/or first run of DSA |
| First pass reperfusion | intraoperative, immediately after the first pass | First pass reperfusion refers to achievement of recanalization by single pass, near-complete to complete recanalization of the occlusion site (eTICI 2c or 3) and no need for rescue treatment |
| Successful reperfusion | immediately after the endovascular intervention | successful reperfusion is defined as extended Treatment In Cerebral Ischemia (eTICI) grades of 2b, 2c or 3 |
| Recanalization | at 24 (±12) hours | — |
Countries
China
Contacts
CONTACTGaoting Ma, MD
PRINCIPAL_INVESTIGATORJunwei Hao, MD, PhD
Xuanwu Hospital, Beijing
Outcome results
None listed