The Efficacy and Safety of Tirofiban Enhanced Antiplatelet Therapy in the Treatment of Ruptured Intracranial Aneurysms With Stent

NCT07818083 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: MRCTA,ECFAH of FMU[2026]6572023ZD0505102
• Study Type: interventional
• Target: 622
• Locations: 0 countries
• Sites: N/A

Brief Summary

This multicenter prospective randomized controlled study will enroll patients with ruptured intracranial aneurysms receiving stent-assisted coiling across multiple Chinese medical centers. The investigators aim to evaluate the efficacy and safety of tirofiban-enhanced antiplatelet therapy versus conventional dual antiplatelet treatment on the 90-day neurological prognosis and major adverse cerebrovascular events of enrolled subjects.

Conditions

Ruptured Intracranial Aneurysms; Subarachnoid Hemorrhage, Aneurysmal

Keywords

Subarachnoid Hemorrhage; Ruptured Intracranial Aneurysms; Tirofiban; Dual Antiplatelet Therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days After Endovascular Treatment

  90 days after stent-assisted embolization

Secondary Outcomes (6)

• Incidence of new cerebral infarction within 7 days after treatment

  Within 7 days after treatment

• Incidence of extracranial thromboembolic events within 7 days after treatment

  Within 7 days after treatment

• Rate of complete aneurysm occlusion after endovascular treatment

  Immediately after procedure

• Aneurysm recurrence rate at 3 months after treatment

  3 months after treatment

• Functional outcome assessed by the modified Rankin Scale at 30 days

  30 days after treatment

Study Arms (2)

Enhanced Antiplatelet Group

EXPERIMENTAL

All subjects receive oral aspirin 300mg plus clopidogrel 300mg 2 hours before operation. After stent deployment, tirofiban 5μg/kg is intravenously bolus injected within 20 seconds, followed by continuous intravenous infusion at 0.075μg/(kg·min) for 24 hours. Long-term oral aspirin 100mg and clopidogrel 75mg daily are administered for 90 days after bridging antiplatelet therapy.

Drug: Tirofiban+Oral Dual Antiplatelet Therapy

Conventional Antiplatelet Group

PLACEBO COMPARATOR

All subjects receive oral aspirin 300mg plus clopidogrel 300mg 2 hours before operation. After stent deployment, equal volume normal saline is intravenously bolus injected and continuously pumped for 24 hours with the same duration. Long-term oral aspirin 100mg and clopidogrel 75mg daily are maintained for 90 days.

Drug: Dual Antiplatelet Therapy plus Normal Saline

Interventions

Tirofiban+Oral Dual Antiplatelet Therapy DRUG

Preoperative oral loading dose: Aspirin 300 mg and Clopidogrel 300 mg. After stent deployment, tirofiban 5 μg/kg intravenous bolus, then continuous infusion at 0.075 μg/(kg・min) for 24 hours. Postoperative maintenance: oral Aspirin 100 mg and Clopidogrel 75 mg once daily for 90 days.

Enhanced Antiplatelet Group

Dual Antiplatelet Therapy plus Normal Saline DRUG

Aspirin 300 mg and Clopidogrel 300 mg. After stent deployment, equal volume normal saline is given via intravenous bolus and continuous infusion for 24 hours. Postoperative maintenance: oral Aspirin 100 mg and Clopidogrel 75 mg once daily for 90 days.

Conventional Antiplatelet Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years; Acute subarachnoid hemorrhage confirmed by head CT, with a WFNS grade of 1-4; DSA-confirmed aneurysmal SAH treated with successful stent deployment; Surgical intervention performed within 72 hours after symptom onset.

You may not qualify if:

• Blood blister-like aneurysms or recurrent aneurysms; Abnormal coagulation profiles (INR \>1.5 or platelet count \<100 × 10⁹/L); Pregnancy, peripartum status, or lactation; Secondary aneurysm rupture due to infection, trauma, tumor invasion, vascular malformation, moyamoya disease, or other pathological causes; Concomitant intracranial hemorrhage; Hypersensitivity to amikacin, ceftriaxone, or related drugs; Autoimmune diseases (e.g., systemic lupus erythematosus); Severe comorbidities, life expectancy ≤3 months, or other investigator-determined reasons precluding enrollment.

Sponsors & Collaborators

• First Affiliated Hospital of Fujian Medical University: lead

Related Publications (32)

• Liang XD, Wang ZL, Li TX, He YK, Bai WX, Wang YY, Zhou GY. Safety and efficacy of a new prophylactic tirofiban protocol without oral intraoperative antiplatelet therapy for endovascular treatment of ruptured intracranial aneurysms. J Neurointerv Surg. 2016 Nov;8(11):1148-1153. doi: 10.1136/neurintsurg-2015-012055. Epub 2015 Nov 27.

  PMID: 26614492 RESULT

• Reddy D, Fallah A, Petropoulos JA, Farrokhyar F, Macdonald RL, Jichici D. Prophylactic magnesium sulfate for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Neurocrit Care. 2014 Oct;21(2):356-64. doi: 10.1007/s12028-014-9964-0.

  PMID: 24619389 RESULT

• Jeon JS, Sheen SH, Hwang G, Kang SH, Heo DH, Cho YJ. Intravenous magnesium infusion for the prevention of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2012 Aug;52(2):75-9. doi: 10.3340/jkns.2012.52.2.75. Epub 2012 Aug 31.

  PMID: 23091662 RESULT

• Vergouwen MD, de Haan RJ, Vermeulen M, Roos YB. Effect of statin treatment on vasospasm, delayed cerebral ischemia, and functional outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update. Stroke. 2010 Jan;41(1):e47-52. doi: 10.1161/STROKEAHA.109.556332. Epub 2009 Oct 29.

  PMID: 19875741 RESULT

• Shen J, Huang KY, Zhu Y, Pan JW, Jiang H, Weng YX, Zhan RY. Effect of statin treatment on vasospasm-related morbidity and functional outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Neurosurg. 2017 Aug;127(2):291-301. doi: 10.3171/2016.5.JNS152900. Epub 2016 Oct 7.

  PMID: 27715439 RESULT

• Togashi K, Joffe AM, Sekhar L, Kim L, Lam A, Yanez D, Broeckel-Elrod JA, Moore A, Deem S, Khandelwal N, Souter MJ, Treggiari MM. Randomized pilot trial of intensive management of blood pressure or volume expansion in subarachnoid hemorrhage (IMPROVES). Neurosurgery. 2015 Feb;76(2):125-34; discussion 134-5; quiz 135. doi: 10.1227/NEU.0000000000000592.

  PMID: 25549192 RESULT

• Loan JJM, Wiggins AN, Brennan PM. Medically induced hypertension, hypervolaemia and haemodilution for the treatment and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage: systematic review. Br J Neurosurg. 2018 Apr;32(2):157-164. doi: 10.1080/02688697.2018.1426720. Epub 2018 Jan 17.

  PMID: 29338431 RESULT

• Choudhari K. Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study. Neurosurgery. 2002 May;50(5):1170-1; author reply 1171-2. doi: 10.1097/00006123-200205000-00057. No abstract available.

  PMID: 11987280 RESULT

• Lennihan L, Mayer SA, Fink ME, Beckford A, Paik MC, Zhang H, Wu YC, Klebanoff LM, Raps EC, Solomon RA. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial. Stroke. 2000 Feb;31(2):383-91. doi: 10.1161/01.str.31.2.383.

  PMID: 10657410 RESULT

• Tejada JG, Taylor RA, Ugurel MS, Hayakawa M, Lee SK, Chaloupka JC. Safety and feasibility of intra-arterial nicardipine for the treatment of subarachnoid hemorrhage-associated vasospasm: initial clinical experience with high-dose infusions. AJNR Am J Neuroradiol. 2007 May;28(5):844-8.

  PMID: 17494654 RESULT

• Stuart RM, Helbok R, Kurtz P, Schmidt M, Fernandez L, Lee K, Badjatia N, Mayer SA, Lavine S, Meyers P, Connolly ES, Claassen J. High-dose intra-arterial verapamil for the treatment of cerebral vasospasm after subarachnoid hemorrhage: prolonged effects on hemodynamic parameters and brain metabolism. Neurosurgery. 2011 Feb;68(2):337-45; discussion 345. doi: 10.1227/NEU.0b013e318201be47.

  PMID: 21135735 RESULT

• Shankar JJ, dos Santos MP, Deus-Silva L, Lum C. Angiographic evaluation of the effect of intra-arterial milrinone therapy in patients with vasospasm from aneurysmal subarachnoid hemorrhage. Neuroradiology. 2011 Feb;53(2):123-8. doi: 10.1007/s00234-010-0720-7. Epub 2010 Jun 5.

  PMID: 20549498 RESULT

• Linfante I, Delgado-Mederos R, Andreone V, Gounis M, Hendricks L, Wakhloo AK. Angiographic and hemodynamic effect of high concentration of intra-arterial nicardipine in cerebral vasospasm. Neurosurgery. 2008 Dec;63(6):1080-6; discussion 1086-7. doi: 10.1227/01.NEU.0000327698.66596.35.

  PMID: 19057319 RESULT

• Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008 Mar;39(3):893-8. doi: 10.1161/STROKEAHA.107.492447. Epub 2008 Jan 31.

  PMID: 18239182 RESULT

• Feng L, Fitzsimmons BF, Young WL, Berman MF, Lin E, Aagaard BD, Duong H, Pile-Spellman J. Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience. AJNR Am J Neuroradiol. 2002 Sep;23(8):1284-90.

  PMID: 12223366 RESULT

• Badjatia N, Topcuoglu MA, Pryor JC, Rabinov JD, Ogilvy CS, Carter BS, Rordorf GA. Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. AJNR Am J Neuroradiol. 2004 May;25(5):819-26.

  PMID: 15140728 RESULT

• Al-Mufti F, Amuluru K, Damodara N, Dodson V, Roh D, Agarwal S, Meyers PM, Connolly ES Jr, Schmidt MJ, Claassen J, Park S. Admission neutrophil-lymphocyte ratio predicts delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. J Neurointerv Surg. 2019 Nov;11(11):1135-1140. doi: 10.1136/neurintsurg-2019-014759. Epub 2019 Apr 12.

  PMID: 30979846 RESULT

• Aoki R, Shimoda M, Oda S, Imai M, Shigematsu H, Matsumae M. Clinical Significance of the CSF Pulsation Flow Sign in the Foramen of Monro on FLAIR in Patients with Aneurysmal SAH -Preliminary Report. Neurol Med Chir (Tokyo). 2019 Jul 15;59(7):271-280. doi: 10.2176/nmc.oa.2018-0294. Epub 2019 May 9.

  PMID: 31068544 RESULT

• Schmidt JM, Wartenberg KE, Fernandez A, Claassen J, Rincon F, Ostapkovich ND, Badjatia N, Parra A, Connolly ES, Mayer SA. Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage. J Neurosurg. 2008 Dec;109(6):1052-9. doi: 10.3171/JNS.2008.109.12.1052.

  PMID: 19035719 RESULT

• Rabinstein AA, Friedman JA, Weigand SD, McClelland RL, Fulgham JR, Manno EM, Atkinson JL, Wijdicks EF. Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke. 2004 Aug;35(8):1862-6. doi: 10.1161/01.STR.0000133132.76983.8e. Epub 2004 Jun 24.

  PMID: 15218156 RESULT

• Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. doi: 10.1161/STROKEAHA.110.589275. Epub 2010 Aug 26.

  PMID: 20798370 RESULT

• Macdonald RL, Hunsche E, Schuler R, Wlodarczyk J, Mayer SA. Quality of life and healthcare resource use associated with angiographic vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2012 Apr;43(4):1082-8. doi: 10.1161/STROKEAHA.111.634071. Epub 2012 Feb 9.

  PMID: 22328549 RESULT

• Ten Brinck MFM, de Vries J, Bartels RHMA, Grotenhuis JA, Boogaarts HD. NeuroForm Atlas Stent-Assisted Coiling: Preliminary Results. Neurosurgery. 2019 Jan 1;84(1):179-189. doi: 10.1093/neuros/nyy048.

  PMID: 29579261 RESULT

• Nishido H, Piotin M, Bartolini B, Pistocchi S, Redjem H, Blanc R. Analysis of complications and recurrences of aneurysm coiling with special emphasis on the stent-assisted technique. AJNR Am J Neuroradiol. 2014 Feb;35(2):339-44. doi: 10.3174/ajnr.A3658. Epub 2013 Aug 1.

  PMID: 23907240 RESULT

• Shen G, Jia Z, Zhao L, Lu G, Liu S, Shi H. The safety and efficacy of a low dose of tirofiban for early complications during and after stent-assisted coiling of ruptured intracranial aneurysms: A propensity matching study. Clin Neurol Neurosurg. 2022 Mar;214:107132. doi: 10.1016/j.clineuro.2022.107132. Epub 2022 Jan 15.

  PMID: 35151058 RESULT

• Ma Y, Jia C, Zhang T, Feng Y, Chen X, Zhao W. Safety and efficacy of intravenous tirofiban for stent-assisted coiling in acutely ruptured intracranial aneurysms: A single center experience. Interv Neuroradiol. 2022 Aug;28(4):476-481. doi: 10.1177/15910199211042463. Epub 2021 Sep 13.

  PMID: 34515564 RESULT

• Zanaty M, Allan L, Samaniego EA, Piscopo A, Ryan E, Torner JC, Hasan D. Phase 1/2a Trial of ISPASM. Stroke. 2021 Dec;52(12):3750-3758. doi: 10.1161/STROKEAHA.121.034578. Epub 2021 Sep 2.

  PMID: 34470496 RESULT

• Yoon CH, Lee HW, Kim YS, Lee SW, Yeom JA, Roh J, Baik SK. Preliminary Study of Tirofiban Infusion in Coil Embolization of Ruptured Intracranial Aneurysms. Neurosurgery. 2018 Jan 1;82(1):76-84. doi: 10.1093/neuros/nyx177.

  PMID: 28419294 RESULT

• Tantry US, Gurbel PA. Antiplatelet drug resistance and variability in response: the role of antiplatelet therapy monitoring. Curr Pharm Des. 2013;19(21):3795-815. doi: 10.2174/1381612811319210006.

  PMID: 23286432 RESULT

• Yang H, Li Y, Jiang Y. Insufficient platelet inhibition and thromboembolic complications in patients with intracranial aneurysms after stent placement. J Neurosurg. 2016 Aug;125(2):247-53. doi: 10.3171/2015.6.JNS1511. Epub 2015 Nov 20.

  PMID: 26587657 RESULT

• King B, Vaziri S, Singla A, Fargen KM, Mocco J. Clinical and angiographic outcomes after stent-assisted coiling of cerebral aneurysms with Enterprise and Neuroform stents: a comparative analysis of the literature. J Neurointerv Surg. 2015 Dec;7(12):905-9. doi: 10.1136/neurintsurg-2014-011457. Epub 2014 Oct 28.

  PMID: 25352581 RESULT

• Zi W, Song J, Kong W, Huang J, Guo C, He W, Yu Y, Zhang B, Geng W, Tan X, Tian Y, Liu Z, Cao M, Cheng D, Li B, Huang W, Liu J, Wang P, Yu Z, Liang H, Yang S, Tang M, Liu W, Huang X, Liu S, Tang Y, Wu Y, Yao L, Shi Z, He P, Zhao H, Chen Z, Luo J, Wan Y, Shi Q, Wang M, Yang D, Chen X, Huang F, Mu J, Li H, Li Z, Zheng J, Xie S, Cai T, Peng Y, Xie W, Qiu Z, Liu C, Yue C, Li L, Tian Y, Yang D, Miao J, Yang J, Hu J, Nogueira RG, Wang D, Saver JL, Li F, Yang Q; RESCUE BT2 Investigators. Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion. N Engl J Med. 2023 Jun 1;388(22):2025-2036. doi: 10.1056/NEJMoa2214299.

  PMID: 37256974 RESULT

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Fuxin Lin, MD

CONTACT

+86 13600893154; lfxstudy@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2026
• First Posted: September 14, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 14, 2026

Record last verified: 2026-09