Stroke, Acute IschemicPhase 3NEWLINENCT07727395
INtra-arterial AltEplase folloWing successfuL reperfusIoN After mEchanical Thrombectomy
A Phase 3 study testing Alteplase and Endovascular thrombectomy in people with Stroke, Acute Ischemic and Large Vessel Occlusion, run by 115 People's Hospital at 11 sites in Vietnam.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Acute Ischemic, Large Vessel Occlusion, Thrombectomy
- What is being tested?
- Alteplase and Endovascular thrombectomy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 416 participants
- Where
- 11 sitesVietnam
- Study dates
- 1 Aug 2026to 31 Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old.
- No significant pre-stroke functional disability (pre-stroke mRS 0-1)
- Clinical diagnosis of acute ischemic stroke with anterior LVO
- 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).
- Baseline NIHSS of 6 - 25
- 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
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- 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)
- 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.
- Informed consent obtained from patient or acceptable patient surrogate.
Who cannot join
- mRS score ≥ 2 before stroke onset
- Anticipated advanced comorbid disease with life expectancy < 12 months
- Acute head trauma
- Severe hypertension with SBP > 185 mmHg or DBP > 110 mmHg and refractory to treatment.
- Any active or recent major bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 30 days.
- Contraindication to recombinant human tissue plasminogen activator (rt-PA) (except time to therapy).
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- Women who are pregnant at stroke onset.
- Recent intracranial surgery in the past 30 days.
- Known genetic or acquired bleeding disposition with anticoagulation factor deficiency.
- Coagulation disorder with INR > 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset).
- Platelet count < 50 G/L.
- Blood glucose < 2,8 mmol/L (50 mg/dl) or > 22,2 mmol/L (400 mg/dl)
- Known severe renal insufficiency with glomerular filtration rate < 30 ml/min or blood creatinine > 220 µmol/L (2,5 mg/dl).
- Requiring hemodialysis or peritoneal dialysis
- Suspected vascular occlusion as a result of infective endocarditis
- Suspected cerebral vasculitis based on medical history and/or angiographic evaluation.
- Suspected aortic dissection
- Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast, heparin.
- Acute ischemic stroke with significant mass effect or evidence of midline shift on baseline neuroimaging, or clinical signs of brain herniation
- Suspected acute ischemic stroke involving multiple vascular territories or occlusion of two or more distinct vascular systems on neuroimaging
- Evidence of intracranial hemorrhage (including hemorrhagic transformation) on neuroimaging
- Brain tumor (with significant mass effect)
- Stent placement and other situations during the EVT procedure that requires antiplatelet therapy or anti coagulation within the first 24 hours.
- Extracranial segment occlusion of the ICA and post-procedural etiology suggests vascular dissection.
- Intravenous heparin administration (however, heparinised saline flushes are allowed)
- Procedure time > 90 min
- Number of thrombectomy passes > 5
- Complications occur during EVT: Vascular rupture, dissection, or contrast extravasation
- Complete clinical recovery after rapid recanalization.
- Participation in other interventional randomized clinical trials that may confound the outcome assessment of the study.
- 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).
- Unlikely to be available for 90-day follow-up
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
Vietnam11 sites, 11 recruiting
- Recruiting
Chau Doc General Hospital
An Giang, 90000
Duc Minh Ha, Dr, +84918752382, drstroke1977@gmail.com
- Recruiting
Can Tho Central General Hospital
Can Tho, 900000
Duc T Ha, PhD, 0989216130, hatanduc@gmail.com
- Recruiting
Da Nang Hospital
Da Nang, 550000
Hai Q Duong, 0983091309, quanghaidr.icu@gmail.com
Thien Q Le, Dr
- Recruiting
Hanoi Medical University Hospital
Hà Nội, 100000
Hai H Bui, Assoc. Prof, 0984128080, hoangbuihai@hmu.edu.vn
Hung D Vu, MsC, hunghmu10101989@gmail.com
- Not yet recruiting
Military Hospital 103
Hà Nội, 100000
Thuan D Do, Assoc., 0982583597, Dothuanvien103@gmail.com
Hai D Nguyen, MsC
- Recruiting
Viet Tiep Friendship Hospital
Haiphong, 180000
Lam D Phung, PhD, 0915727288, duclam1971@gmail.com
Duong B Dao, MsC
- Not yet recruiting
175 Military Hospital
Ho Chi Minh City, 700000
Nghia TT Hoang, PhD, 0976035999, dr.hnghia@gmail.com
- Recruiting
People's Hospital 115
Ho Chi Minh City, 700000
Thang H Nguyen, Assoc. Prof, 0909982115, nguyenhuythang115@gmail.com
Binh N Pham, PhD, 0909333538, pnbinh@gmail.com
- Recruiting
Thong Nhat Hospital
Ho Chi Minh City, 700000
Yen MH Trang, MsC, (+84) 908060098, trangmonghaiyen@gmail.com
Nga TP Nguyen, Dr, +84908190633, drngatk70@yahoo.com
- Not yet recruiting
University Medical Center
Ho Chi Minh City, 700000
Thang Ba Nguyen, PhD, +84913888010, thangnb72@gmail.com
Suong Thi Ngoc Le, MsC, +84973877791, lengocsuongtg@gmail.com
- Recruiting
Hue Central Hospital
Huế, 530000
Huynh V Le, Msc, 0944971509, Levuhuynh01@gmail.com
About this study
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.
Read the 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.
- Conditions
- Stroke, Acute Ischemic, Large Vessel Occlusion, Thrombectomy
- Being tested
- Alteplase, Endovascular thrombectomy
- Keywords
- Intra-artery thrombolysis, successful reperfusion
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlteplaseDrug
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 thrombectomyDevice
Endovascular thrombectomy performed according to current international and local guidelines using approved endovascular techniques and devices.
| Study group | Role | What they receive |
|---|---|---|
| Standard medical treatment | Active comparator | Endovascular thrombectomy + Best Medical Management Receives: Device: Endovascular thrombectomy |
| Adjunct intra-arterial thrombolysis following successful thrombectomy | Experimental | Endovascular thrombectomy + Adjunct intra-arterial alteplase + Best Medical Management Receives: Drug: Alteplase; Device: Endovascular thrombectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified 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.
Measured: 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.
Measured: 24hours post EVT
Secondary outcomes (8)
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).
Measured: day 90 post treatment
SAFETY OUTCOME: Mortality at 90 days
Mortality at 90 days
Measured: 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.
Measured: day 90 post treatment
NIHSS at 24h
The proportion of NIHSS 0-1 or ≥10 points reduction at 24 ±12 hours
Measured: 24 ±12 hours post EVT
mRS 0-2 at 90 day
The proportion of mRS 0-2 at 90 ± 15 days
Measured: 90 day post EVT
Any ICH
Any ICH within 24 ± 12 hours (Heidelberg criteria)
Measured: 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.
Measured: 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.
Measured: 12 months ± 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start1 Aug 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Stroke, Acute IschemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An investigator-initiated, prospective, multicenter, randomized,open-label, parallel-group, blinded-endpoint assessment (PROBE) clinical trial.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 416 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 115 People's Hospital
- Sponsor type
- Other government
- Collaborators
- Ho Chi Minh City Stroke Association
- Responsible party
- Principal investigator, Trung Nguyen, 115 People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07727395
- Sponsor's protocol ID
- HSA-NEWLINE-2026-001
- Acronym
- NEWLINE
- Status last verified
- Sep 2026
- First submitted
- 15 Jul 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the results reported in the primary publication will be shared. This includes baseline demographic and clinical characteristics, imaging variables, treatment allocation, efficacy outcomes, safety outcomes, and follow-up data collected through 90 days.
Publications
Yang X, He X, Pan D, Xu Y, Peng H, Li K, Zhang M, Zhu Y, Chen Y, He B, Zhou H, Li J, Hou H, Sun H, Liu Y, Tang Y. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. BMJ Open. 2024 Nov 5;14(11):e091059. doi: 10.1136/bmjopen-2024-091059.
PubMed 39500603Huo X, Luo G, Sun D, Nguyen T, Abdalkader M, Chen W, Yao X, Yuan G, Yi T, Han H, Pan Y, Jovin TG, Liebeskind DS, Liu L, Zhao X, Ren Z, Wang Y, Wang Y, Yan B, Miao Z. Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial. Stroke Vasc Neurol. 2025 Aug 26;10(4):508-513. doi: 10.1136/svn-2024-003318.
PubMed 39357896Renu A, Millan M, San Roman L, Blasco J, Marti-Fabregas J, Terceno M, Amaro S, Serena J, Urra X, Laredo C, Barranco R, Camps-Renom P, Zarco F, Oleaga L, Cardona P, Castano C, Macho J, Cuadrado-Godia E, Vivas E, Lopez-Rueda A, Guimaraens L, Ramos-Pachon A, Roquer J, Muchada M, Tomasello A, Davalos A, Torres F, Chamorro A; CHOICE Investigators. Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial. JAMA. 2022 Mar 1;327(9):826-835. doi: 10.1001/jama.2022.1645.
PubMed 35143603Renu A, de la Riva P, Delgado-Mederos R, Dorado L, Fernandez-Couto MD, Herrera-Isasi M, Lopez Hernandez N, Morales A, Morales-Caba L, Camps-Renom P, Singla A, Terceno M, Vega P, Amaro S, Blasco J, Laredo C, Leira EC, Oleaga L, Serena J, Urra X, Werner M, Hernandez Fernandez F, Valls J, Arenillas Lara JF, Freijo MDM, Perez de la Ossa N, San Roman L, Torres F, Castellanos M, Davalos A, Chamorro A; CHOICE 2 Investigators. Chemical Optimization of Cerebral Embolectomy 2 (CHOICE 2) trial: study protocol. Stroke Vasc Neurol. 2025 Dec 3:svn-2025-004279. doi: 10.1136/svn-2025-004279. Online ahead of print.
PubMed 41339082