INtra-arterial AltEplase folloWing successfuL reperfusIoN After mEchanical Thrombectomy

NCT07727395 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: HSA-NEWLINE-2026-001
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 9

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.

Conditions

Stroke, Acute Ischemic; Large Vessel Occlusion; Thrombectomy

Keywords

Intra-artery thrombolysis; successful reperfusion

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  24hours post EVT

Secondary Outcomes (8)

• The shift analysis of 90-day mRS

  day 90 post treatment

• SAFETY OUTCOME: Mortality at 90 days

  Day 90 post endovascular treatment

• Quality of life at 90 days

  day 90 post treatment

• NIHSS at 24h

  24 ±12 hours post EVT

• mRS 0-2 at 90 day

  90 day post EVT

Study Arms (2)

Standard medical treatment

ACTIVE COMPARATOR

Endovascular thrombectomy + Best Medical Management

Device: Endovascular thrombectomy

Adjunct intra-arterial thrombolysis following successful thrombectomy

EXPERIMENTAL

Endovascular thrombectomy + Adjunct intra-arterial alteplase + Best Medical Management

Drug: Alteplase; Device: Endovascular thrombectomy

Interventions

Alteplase DRUG

Intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) administered immediately after successful endovascular thrombectomy in addition to best medical management.

Adjunct intra-arterial thrombolysis following successful thrombectomy

Endovascular thrombectomy DEVICE

Endovascular thrombectomy performed according to current international and local guidelines using approved endovascular techniques and devices.

Adjunct intra-arterial thrombolysis following successful thrombectomy; Standard medical treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• 115 People's Hospital: lead
• Ho Chi Minh City Stroke Association: collaborator

Study Sites (9)

Can Tho Central General Hospital

Can Tho, 900000, Vietnam

Location

Da Nang Hospital

Da Nang, 550000, Vietnam

Location

Viet Tiep Friendship Hospital

Haiphong, 180000, Vietnam

Location

Hanoi Medical University Hospital

Hà Nội, 100000, Vietnam

Location

Military Hospital 103

Hà Nội, 100000, Vietnam

Location

175 Military Hospital

Ho Chi Minh City, 700000, Vietnam

Location

People's Hospital 115

Ho Chi Minh City, 700000, Vietnam

Location

Thong Nhat Hospital

Ho Chi Minh City, 700000, Vietnam

Location

Hue Central Hospital

Huế, 530000, Vietnam

Location

Related Publications (4)

• 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.

  PMID: 39500603 RESULT

• Huo 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.

  PMID: 39357896 RESULT

• Renu 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.

  PMID: 35143603 RESULT

• Renu 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.

  PMID: 41339082 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Central Study Contacts

Thang H Nguyen, Assoc. Prof.

CONTACT

+84909982115; nguyenhuythang115@gmail.com

Trung Q Nguyen, MsC

CONTACT

+84938477516; quoctrungyds09@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Stroke Neurologist

Model Details: An investigator-initiated, prospective, multicenter, randomized,open-label, parallel-group, blinded-endpoint assessment (PROBE) clinical trial.

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 27, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 12 months after publication of the primary study results and continuing for 10 years.
• Access Criteria: Qualified researchers with a methodologically sound research proposal may request access to de-identified individual participant data and supporting documents. Requests will be reviewed and approved by the Steering Committee. Access will be granted after execution of a data-sharing agreement and provided through a secure data-sharing platform or secure file transfer.

Locations

VN (9)