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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
416
Intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) administered immediately after successful endovascular thrombectomy in addition to best medical management.
Endovascular thrombectomy performed according to current international and local guidelines using approved endovascular techniques and devices.
Chau Doc General Hospital
An Giang, Vietnam
RECRUITINGCan Tho Central General Hospital
Can Tho, Vietnam
RECRUITINGDa Nang Hospital
Da Nang, Vietnam
RECRUITINGViet Tiep Friendship Hospital
Haiphong, Vietnam
RECRUITINGHanoi Medical University Hospital
Hà Nội, Vietnam
NOT_YET_RECRUITINGMilitary Hospital 103
Hà Nội, Vietnam
NOT_YET_RECRUITING175 Military Hospital
Ho Chi Minh City, Vietnam
NOT_YET_RECRUITINGPeople's Hospital 115
Ho Chi Minh City, Vietnam
RECRUITINGThong Nhat Hospital
Ho Chi Minh City, Vietnam
RECRUITINGHue Central Hospital
Huế, Vietnam
RECRUITINGModified Rankin Scale at day 90
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.
Time frame: 90 days post treatment
SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours.
Symptomatic intracranial hemorrhage (sICH) will be classified according to the Heidelberg Bleeding Classification.
Time frame: 24hours post EVT
The shift analysis of 90-day mRS
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).
Time frame: day 90 post treatment
SAFETY OUTCOME: Mortality at 90 days
Mortality at 90 days
Time frame: Day 90 post endovascular treatment
Quality of life at 90 days
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.
Time frame: day 90 post treatment
NIHSS at 24h
The proportion of NIHSS 0-1 or ≥10 points reduction at 24 ±12 hours
Time frame: 24 ±12 hours post EVT
mRS 0-2 at 90 day
The proportion of mRS 0-2 at 90 ± 15 days
Time frame: 90 day post EVT
Any ICH
Any ICH within 24 ± 12 hours (Heidelberg criteria)
Time frame: 24 hour post EVT
Final eTICI reperfusion grade
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.
Time frame: Immediately after completion of intra-arterial alteplase administration.
To evaluate the incremental cost-effectiveness and cost-utility of adjunctive intra-arterial thrombolysis following successful angiographic reperfusion.
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.
Time frame: 12 months ± 1 month
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