Tirzepatide in Thrombectomy-Treated Acute Ischemic Stroke: A Randomized Trial

NCT07734792 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: JD-LK2026069-A01
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 1

Brief Summary

Acute ischemic stroke caused by blockage of a large artery in the brain is one of the leading causes of death and long-term disability worldwide. For patients with this type of stroke, endovascular thrombectomy (EVT), a procedure that removes the blood clot and restores blood flow to the brain, has become the standard treatment. However, even when blood flow is successfully restored, many patients continue to experience disability because of ongoing brain injury caused by inflammation, oxidative stress, and damage to brain cells after the stroke. This study aims to evaluate whether tirzepatide, a medication that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) pathways, can improve recovery in patients with acute ischemic stroke caused by large vessel occlusion who receive thrombectomy. Tirzepatide is currently approved for the treatment of conditions such as type 2 diabetes and obesity. Previous studies have shown that tirzepatide can improve blood sugar control, reduce body weight, and provide beneficial effects on cardiovascular health. Laboratory studies and early clinical evidence suggest that medications targeting GLP-1 and GIP pathways may also have protective effects on the brain by reducing inflammation, protecting brain cells, improving blood vessel function, and supporting recovery after stroke. In this study, eligible patients with acute ischemic stroke caused by blockage of a major brain artery will be randomly assigned to receive either tirzepatide plus standard stroke care or standard stroke care alone. Participants will receive two subcutaneous injections of tirzepatide: the first dose before the thrombectomy procedure and the second dose 7 days after the procedure. The study will include multiple hospitals and will use independent assessment of outcomes to ensure reliable evaluation of treatment effects. The primary purpose of this study is to determine whether early treatment with tirzepatide can improve functional recovery 90 days after stroke, measured by the patient's ability to perform daily activities and live independently. The study will also evaluate whether tirzepatide is safe in patients with acute ischemic stroke by monitoring adverse events, complications, and other clinical outcomes. The findings from this study may provide important evidence for a new treatment approach to improve recovery after thrombectomy and reduce disability among patients with severe ischemic stroke.

Conditions

Acute Ischemic Stroke (AIS)

Keywords

acute ischemic stroke; endovascular thrombectomy; large vessel occlusion; tirzepatide; GLP-1/GIP

Outcome Measures

Primary Outcomes (2)

• The primary efficacy outcome: Proportion of patients achieving an excellent functional outcome

  A excellent functional outcome is defined as modified Rankin Scale (mRS) score of 0-1 at 90 days. The Modified Rankin Scale ranges from 0 to 6, where 0 indicates no symptoms, 1 indicates symptoms without significant disability, 2 indicates slight disability, 3 indicates moderate disability, 4 indicates moderately severe disability, 5 indicates severe disability, and 6 indicates death. Higher scores indicate worse functional outcomes.

  90 ± 7 days after randomization

• The primary safety outcome: All-cause mortality

  death from any cause within 90 days

  90 ± 7 days

Secondary Outcomes (3)

• The secondary efficacy outcome: Distribution of mRS scores at 90 days after randomization

  90 ± 7 days

• The secondary efficacy outcome: Proportion of patients achieving an good functional outcome

  90 ± 7 days

• The secondary safety outcome: Symptomatic intracranial hemorrhage (sICH)

  within 48 hours after thrombectomy

Other Outcomes (8)

• Early neurological improvement

  7 ± 2 Days

• Recanalization rate of the target LVO vessel

  at 7 days after EVT or hospital discharge

• Health-related quality of life

  90 ± 7 days

Study Arms (2)

Tirzepatide Intervention Group

EXPERIMENTAL

Participants will receive two subcutaneous injections of tirzepatide: the first administered before EVT and the second administered 7 days after EVT, in addition to standard medical care

Drug: Tirzepatide; Other: Standard Medical Care (SMC)

Control Group

ACTIVE COMPARATOR

Participants will receive EVT and standard medical care without tirzepatide.

Other: Standard Medical Care (SMC)

Interventions

Tirzepatide DRUG

Participants will receive two subcutaneous injections of tirzepatide (5 mg each): the first administered before EVT and the second administered 7 days after EVT, in addition to standard medical care

Also known as: Mounjaro

Tirzepatide Intervention Group

Standard Medical Care (SMC) OTHER

Participants will receive EVT and standard medical care without tirzepatide.

Control Group; Tirzepatide Intervention Group

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Age \>18 years and ≤80 years;
• Acute ischemic stroke with imaging-confirmed anterior large vessel occlusion at:
• Terminal ICA,
• M1 segment of the middle cerebral artery, or
• Dominant M2 segment;
• NIHSS score between 6 and 25 prior to randomization;
• Alberta Stroke Program Early CT Score (ASPECTS) of 6-10 before randomization;
• Time from symptom onset (or last known well) to planned endovascular thrombectomy within 24 hours;
• Pre-stroke mRS score of 0-1;
• Patients presenting within 6 hours of symptom onset are eligible for direct EVT. Patients presenting between 6 and 24 hours after symptom onset must undergo advanced imaging demonstrating a salvageable perfusion mismatch and meet the DEFUSE-3 criteria: an infarct core volume \<70 mL, a mismatch volume \>15 mL, and a mismatch ratio \>1.8;
• Written informed consent provided by the participant or a legally authorized representative.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• Posterior-circulation large vessel occlusion stroke;
• Receipt of intravenous thrombolysis prior to randomization;
• Simultaneous bilateral anterior-circulation occlusions or concurrent anterior- and posterior-circulation occlusions;
• Intracranial hemorrhage on baseline CT or MRI, including subarachnoid hemorrhage or intracerebral hemorrhage; evidence of large established infarction, defined as:
• ASPECTS \<6,
• Ischemic core volume ≥70 mL on CTP, or
• Infarction involving \>1/3 of the middle cerebral artery territory;
• Active bleeding within the previous month (e.g., gastrointestinal, genitourinary, or retinal hemorrhage), major organ surgery or biopsy within 14 days before stroke onset, or known bleeding diathesis;
• Refractory hypertension despite treatment, defined as persistent systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg;
• Severe hepatic or renal impairment, including:
• Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m²,
• Serum creatinine \>200 μmol/L,
• Child-Pugh Class C or higher liver disease,
• Recurrent unexplained hypoglycemia;

Sponsors & Collaborators

• yifang zhu: lead

Study Sites (1)

The Second Afliated Hospital of SooChow University

Suzhou, Jiangsu, 215004, China

Location

Related Publications (19)

• Kruger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, Schunkert H, Wang SV. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092.

  PMID: 40886075 RESULT

• Furihata K, Mimura H, Urva S, Oura T, Ohwaki K, Imaoka T. A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes. Diabetes Obes Metab. 2022 Feb;24(2):239-246. doi: 10.1111/dom.14572. Epub 2021 Nov 18.

  PMID: 34647404 RESULT

• Wang H, Ko H, Leung TW, Huang J, Sai J, Liang Y, Li H, Zhang J, Cao Q, Zang W, Li Y, Ma SH, Lui WT, Choi J, Chan C, Wong J, Kwok AJ, Ma K, Fan F, Chan A, Ip V, Leung H, Soo Y, Wong KT, Lai B, Chu CM, Leung HS, Hui A, Cheung T, Abrigo J, Li SH, Chan L, Yeung J, Pan S, Yip T, Lui LT, Hung T, Tsang SF, Leng X, Lam B, Mok VCT, Chan RHM, Nguyen TN, Hu W, Che F, Ip BY. Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by reperfusion therapy-a phase 2 randomized trial. Nat Commun. 2025 Dec 14;16(1):11274. doi: 10.1038/s41467-025-66167-z.

  PMID: 41392086 RESULT

• Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, Wilding JPH, Perreault L, Zhang S, Battula R, Bunck MC, Ahmad NN, Jouravskaya I; SURMOUNT-1 Investigators. Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med. 2025 Mar 6;392(10):958-971. doi: 10.1056/NEJMoa2410819. Epub 2024 Nov 13.

  PMID: 39536238 RESULT

• Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25.

  PMID: 34170647 RESULT

• Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornoe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11.

  PMID: 37952131 RESULT

• Holscher C. Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer's and Parkinson's disease models. Neuropharmacology. 2018 Jul 1;136(Pt B):251-259. doi: 10.1016/j.neuropharm.2018.01.040. Epub 2018 Jan 31.

  PMID: 29402504 RESULT

• Wang D, Wang J, Li B, Yang S, Guo F, Zheng B, Wang J. Tirzepatide mitigates Stroke-Induced Blood-Brain barrier disruption by modulating Claudin-1 and C/EBP-alpha pathways. Mol Med. 2025 Jul 23;31(1):263. doi: 10.1186/s10020-025-01312-4.

  PMID: 40702450 RESULT

• Li PC, Liu LF, Jou MJ, Wang HK. The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice. BMC Neurosci. 2016 Jun 13;17(1):37. doi: 10.1186/s12868-016-0272-9.

  PMID: 27296974 RESULT

• Goldenberg RM, Cheng AYY, Fitzpatrick T, Gilbert JD, Verma S, Hopyan JJ. Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists. Stroke. 2022 May;53(5):1813-1822. doi: 10.1161/STROKEAHA.121.038151. Epub 2022 Mar 9.

  PMID: 35259929 RESULT

• Kopp KO, Glotfelty EJ, Li Y, Greig NH. Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment. Pharmacol Res. 2022 Dec;186:106550. doi: 10.1016/j.phrs.2022.106550. Epub 2022 Nov 11.

  PMID: 36372278 RESULT

• Wang C, Gu H, Huo X, Yuan B, Li S, Xu J, Jiang Y, Jing J, Yao X, Li Z, Long F, Ma Z, Zhuang X, Xu L, Jin Y, Huang W, Zhang Y, Wen J, Wang A, Pan Y, Ye W, Yu W, Cheng A, Wang M, Dong Q, Xu A, Wang N, Yang Y, Meng X, Liu L, Zhao X, Li H, Miao Z, Li Z, Wang Y; TASTE-2 investigators. Edaravone dexborneol versus placebo on functional outcomes in patients with acute ischaemic stroke undergoing endovascular thrombectomy (TASTE-2): randomised controlled trial. BMJ. 2026 Jan 7;392:e086850. doi: 10.1136/bmj-2025-086850.

  PMID: 41500725 RESULT

• Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. doi: 10.1056/NEJMoa1713973. Epub 2018 Jan 24.

  PMID: 29364767 RESULT

• Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.

  PMID: 29129157 RESULT

• Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.

  PMID: 26898852 RESULT

• Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.

  PMID: 25671797 RESULT

• Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30.

  PMID: 31662037 RESULT

• Wu S, Wu B, Liu M, Chen Z, Wang W, Anderson CS, Sandercock P, Wang Y, Huang Y, Cui L, Pu C, Jia J, Zhang T, Liu X, Zhang S, Xie P, Fan D, Ji X, Wong KL, Wang L; China Stroke Study Collaboration. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019 Apr;18(4):394-405. doi: 10.1016/S1474-4422(18)30500-3.

  PMID: 30878104 RESULT

• Wang W, Jiang B, Sun H, Ru X, Sun D, Wang L, Wang L, Jiang Y, Li Y, Wang Y, Chen Z, Wu S, Zhang Y, Wang D, Wang Y, Feigin VL; NESS-China Investigators. Prevalence, Incidence, and Mortality of Stroke in China: Results from a Nationwide Population-Based Survey of 480 687 Adults. Circulation. 2017 Feb 21;135(8):759-771. doi: 10.1161/CIRCULATIONAHA.116.025250. Epub 2017 Jan 4.

  PMID: 28052979 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Guodong Xiao, MD.PhD

  The Second Afliated Hospital of SooChow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guodong Xiao, MD.PhD

CONTACT

+8618020289268; gdxiao@suda.edu.cn

Shoujiang You, MD.PhD

CONTACT

+8615995738506; 0319503013@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This study will employ a blinded-endpoint assessment design. Outcome measures, including 90-day mRS assessment, EQ-5D-5L questionnaire, neurological deficit evaluations during hospitalization, and imaging assessments, will be performed by trained investigators who are unaware of treatment allocation. Assessments will be conducted through either face-to-face visits or telephone follow-up.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This study is designed as a multicenter, randomized, controlled trial with blinded endpoint assessment. A total of 430 patients with acute ischemic stroke due to anterior-circulation large vessel occlusion (LVO) who are eligible for endovascular thrombectomy (EVT) will be recruited from 30 participating centers across China. Patients will be stratified by study center and centrally randomized in a 1:1 ratio to receive either early tirzepatide intervention or standard care (control). Participants in the intervention group will receive two subcutaneous injections of tirzepatide: the first administered before EVT and the second on day 7 after the procedure. All participants will be followed for 90 days, and the efficacy and safety of early tirzepatide intervention will be evaluated, with functional outcome at 90 days as the primary efficacy endpoint.

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): August 10, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)