Large Vessel Occlusion, Stroke, Acute Ischemic, Thrombectomy
Conditions
Keywords
Intra-artery thrombolysis, successful reperfusion
Brief summary
The NEWLINE trial is a multicenter, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether adjunctive low-dose intra-arterial alteplase administered immediately after successful endovascular thrombectomy improves functional outcomes in adults with acute ischemic stroke due to anterior circulation large vessel occlusion. Eligible participants achieving successful reperfusion (eTICI 2b-3) within 24 hours of symptom onset will be randomized 1:1 to receive intra-arterial alteplase plus standard care or standard care alone. The primary outcome is excellent functional outcome (modified Rankin Scale score 0-1) at 90 days.
Detailed description
Acute ischemic stroke caused by anterior circulation large vessel occlusion is commonly treated with endovascular thrombectomy (EVT), which achieves successful reperfusion in approximately 85-90% of treated patients. Despite successful reperfusion, many patients remain functionally disabled because of persistent microvascular obstruction, distal embolization, incomplete tissue reperfusion (the "no-reflow" phenomenon), and ischemia-reperfusion injury. The NEWLINE trial is a prospective, multicenter, randomized, open-label, blinded endpoint (PROBE) trial designed to evaluate whether adjunctive low-dose intra-arterial alteplase administered immediately after successful EVT improves functional outcomes compared with standard medical care alone. Eligible adults with acute ischemic stroke due to anterior circulation large vessel occlusion who achieve successful reperfusion (expanded Thrombolysis in Cerebral Infarction \[eTICI\] grade 2b-3) within 24 hours of symptom onset will be randomly assigned in a 1:1 ratio to receive either adjunctive intra-arterial alteplase plus standard care or standard care alone. The primary efficacy outcome is the proportion of participants achieving excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1, at 90 days after randomization. Key safety outcomes include symptomatic intracranial hemorrhage and all-cause mortality. The trial aims to determine whether adjunctive intra-arterial alteplase enhances neurological recovery after successful EVT without increasing the risk of major hemorrhagic complications or death.
Interventions
DRUGAlteplase
Intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) administered immediately after successful endovascular thrombectomy in addition to best medical management.
DEVICEEndovascular thrombectomy
Endovascular thrombectomy performed according to current international and local guidelines using approved endovascular techniques and devices.
Sponsors
115 People's Hospital
Ho Chi Minh City Stroke Association
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The primary efficacy outcome (modified Rankin Scale \[mRS\] score 0-1 at 90 days) will be assessed by independent central outcome assessors who are blinded to treatment allocation, using a standardized structured interview conducted via video or telephone recording. Imaging outcomes will be evaluated by independent neuroradiologists at the Central Imaging Core Laboratory, who will remain blinded to treatment allocation and all clinical outcome data.
Intervention model description
An investigator-initiated, prospective, multicenter, randomized,open-label, parallel-group, blinded-endpoint assessment (PROBE) clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old. 2. No significant pre-stroke functional disability (pre-stroke mRS 0-1) 3. Clinical diagnosis of acute ischemic stroke with anterior LVO 4. Time from symptom onset to randomization within 24 hours, including wake-up stroke or unwitness stroke; the onset time refers to "Last Known Well" (LKW). 5. Baseline NIHSS of 6 - 25 6. Non-contrast CT (NCCT) or diffusion-weighted imaging (DWI)-MRI Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. For patients with available perfusion imaging (CTP/MRP), additional criteria include: Ischemic core volume ≤ 70mL; Mismatch volume ≥ 15 ml; Mismatch ratio ≥ 1.8 7. Evidence of oclussion of the intracranial segment of the internal carotid artery (ICA), or M1 or M2 segment of the middle cerebral artery (MCA) on CT angiography (CTA) or MR angiography (MRA) 8. Treated with EVT resulting eTICI score of 2b-3. Patients with an eTICI score of 2b-3 on the diagnostic cerebral angiography before MT are also eligible for the study. 9. Informed consent obtained from patient or acceptable patient surrogate.
Exclusion criteria
1. mRS score ≥ 2 before stroke onset 2. Anticipated advanced comorbid disease with life expectancy \< 12 months 3. Acute head trauma 4. Severe hypertension with SBP \> 185 mmHg or DBP \> 110 mmHg and refractory to treatment. 5. Any active or recent major bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 30 days. 6. Contraindication to recombinant human tissue plasminogen activator (rt-PA) (except time to therapy). 7. Women who are pregnant at stroke onset. 8. Recent intracranial surgery in the past 30 days. 9. Known genetic or acquired bleeding disposition with anticoagulation factor deficiency. 10. Coagulation disorder with INR \> 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset). 11. Platelet count \< 50 G/L. 12. Blood glucose \< 2,8 mmol/L (50 mg/dl) or \> 22,2 mmol/L (400 mg/dl) 13. Known severe renal insufficiency with glomerular filtration rate \< 30 ml/min or blood creatinine \> 220 µmol/L (2,5 mg/dl). 14. Requiring hemodialysis or peritoneal dialysis 15. Suspected vascular occlusion as a result of infective endocarditis 16. Suspected cerebral vasculitis based on medical history and/or angiographic evaluation. 17. Suspected aortic dissection 18. Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast, heparin. 19. Acute ischemic stroke with significant mass effect or evidence of midline shift on baseline neuroimaging, or clinical signs of brain herniation 20. Suspected acute ischemic stroke involving multiple vascular territories or occlusion of two or more distinct vascular systems on neuroimaging 21. Evidence of intracranial hemorrhage (including hemorrhagic transformation) on neuroimaging 22. Brain tumor (with significant mass effect) 23. Stent placement and other situations during the EVT procedure that requires antiplatelet therapy or anti coagulation within the first 24 hours. 24. Extracranial segment occlusion of the ICA and post-procedural etiology suggests vascular dissection. 25. Intravenous heparin administration (however, heparinised saline flushes are allowed) 26. Procedure time \> 90 min 27. Number of thrombectomy passes \> 5 28. Complications occur during EVT: Vascular rupture, dissection, or contrast extravasation 29. Complete clinical recovery after rapid recanalization. 30. Participation in other interventional randomized clinical trials that may confound the outcome assessment of the study. 31. Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment). 32. Unlikely to be available for 90-day follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale at day 90 | 90 days post treatment | Proportion of participants achieving a Modified Rankin Scale (mRS) score of 0 or 1 at 90 days (±15 days). The Modified Rankin Scale ranges from 0 (no symptoms) to 6 (death). Lower scores indicate better functional outcomes; higher scores indicate worse disability. |
| SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours. | 24hours post EVT | Symptomatic intracranial hemorrhage (sICH) will be classified according to the Heidelberg Bleeding Classification. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The shift analysis of 90-day mRS | day 90 post treatment | Shift analysis of the modified Rankin Scale (mRS) at Day 90 (scores range from 0 to 6, with mRS scores of 5 and 6 combined into a single category representing a very poor outcome; higher scores indicate worse functional outcomes). |
| SAFETY OUTCOME: Mortality at 90 days | Day 90 post endovascular treatment | Mortality at 90 days |
| Quality of life at 90 days | day 90 post treatment | Quality of life at 90 days (±15 days), measured using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. The EQ VAS ranges from 0 (worst imaginable health) to 100 (best imaginable health), with higher scores indicating better health-related quality of life. |
| NIHSS at 24h | 24 ±12 hours post EVT | The proportion of NIHSS 0-1 or ≥10 points reduction at 24 ±12 hours |
| mRS 0-2 at 90 day | 90 day post EVT | The proportion of mRS 0-2 at 90 ± 15 days |
| Any ICH | 24 hour post EVT | Any ICH within 24 ± 12 hours (Heidelberg criteria) |
| Final eTICI reperfusion grade | Immediately after completion of intra-arterial alteplase administration. | Reperfusion will be assessed on the final digital subtraction angiogram using the expanded Thrombolysis in Cerebral Infarction (eTICI) grading scale. The eTICI scale ranges from 0 (no reperfusion) to 3 (complete reperfusion). Higher grades indicate better angiographic reperfusion. |
| To evaluate the incremental cost-effectiveness and cost-utility of adjunctive intra-arterial thrombolysis following successful angiographic reperfusion. | 12 months ± 1 month | Incremental cost-effectiveness and cost-utility of adjunctive intra-arterial thrombolysis following successful angiographic reperfusion, expressed as the incremental cost per quality-adjusted life-year (QALY) gained compared with standard care. |
Countries
Vietnam
Contacts
CONTACTThang H Nguyen, Assoc. Prof.
CONTACTTrung Q Nguyen, MsC
Outcome results
None listed