One Pass Tirofiban In Management of Ischemic Stroke Thrombectomy In China

Ischemic Stroke Clinical Trial

— OPTIMISTIC  

Official title:

Safety and Efficacy of Tirofiban in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy-A Prospective, Randomized, Controlled, Open-Label, Assessor-Blind, Multicenter Clinical Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04851457
• Other study ID #: 2021-OPTIMISTIC
• Status: Completed
• Phase: Phase 2
• Start date: April 6, 2021
• Est. completion date: October 15, 2023

Study information

• Verified date: January 2024
• Source: Shanghai East Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In recent years, the positive results of trials for mechanical thrombectomy (MT) have brought a new era for large artery occlusion patients, especially those beyond the time window of intravenous thrombolysis. However, interventional procedures can cause endothelial injuries leading to local activation of platelet aggregation and subsequent thromboembolic complications or early re-occlusion.Tirofiban is a specific antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, which is considered highly effective against the final common pathway of platelet aggregation and preventing vascular reocclusion. However, there is no consensus on if AIS patients treated with MT also benefit from intravenous tirofiban. This study aims to evaluate the effectiveness and safety of profiles of tirofiban during MT and provide reliable clinical evidence for the treatment of tirofiban in AIS patients.

Description:

This study is a multicenter, prospective, open-label, randomized controlled, blinded-endpoint trial with two parallel groups and a 3-month follow-up. A total of 200 eligible participants recruited from 4-6 stroke centers will be randomly allocated to either an experimental group (intravenous tirofiban + MT therapy) or a control group (MT alone) in a 1:1 ratio. The primary outcome is a composite endpoint, including the rate of recanalisation after the first embolectomy and the risk of symptomatic intracerebral haemorrhage. The secondary outcomes include clinical and neuroimaging outcomes, procedure-related complications, and adverse events to evaluate the effects of MT in combination with tirofiban treatment compared to MT alone in AIS patients. Intention-to-treat (ITT) analysis will be undertaken in this study, and the full analysis set (FAS) population serves as the primary population for the analysis of efficacy data.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 15, 2023
• Est. primary completion date: July 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age 18-85 years (including 18 and 85);

2. Acute ischemic stroke within 24 hours of onset, and NIHSS >5 points;

3. Acute large vessel occlusion, including internal carotid artery, M1 segment of middle cerebral artery, M2 segment of middle cerebral artery;

4. Multimodal CT/MRI imaging was completed before thrombectomy, and the following criteria were met: penumbra>10ml, infarct core volume <70ml, and mismatch rate >1.2;

5. Planned to receive endovascular treatment;

6. Informed consent was obtained.

Exclusion Criteria:

1. History of atrial fibrillation or atrial flutter, or 12-lead ECG before randomization and after admission showing atrial flutter or atrial fibrillation;

2. Treated with intravenous thrombolysis for this stroke or currently taking new oral anticoagulant drugs, warfarin, ticagrelor and other drugs that may increase the risk of bleeding;

3. Pre-stroke disability (pre-stroke mRS score > 2);

4. Severe comorbidity (such as severe cardiopulmonary dysfunction, or the terminal stage of malignant tumors with expected survival less than 90 days);

5. CT shows hypodensity lesions in more than 1/3 of the territory of the middle cerebral artery;

6. Allergy to tirofiban or having any contraindications to the use of tirofiban (patients with active internal bleeding, history of intracranial hemorrhage, intracranial tumors, arteriovenous malformations, and intracranial aneurysms, or patients resulting in thrombocytopenia from the use of tirofiban previously);

7. Contraindications to the contrast agents used in multimodal CT/MRI examination (such as allergy to the contrast agents, etc.);

8. Pregnant or breastfeeding women;

9. Patients currently participating in other clinical study trials;

10. Other conditions determined by the investigator are not suitable for inclusion in this study.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Intravenous tirofiban combination therapy
Patients will enter the tirofiban treatment protocol immediately within half an hour after randomization and prior to the femoral artery puncture. Tirofiban is administered as an intravenous bolus dose of 10 µg/kg injection within 3 min and then by an intravenous infusion at a rate of 0.1 µg/(kg·min) for 24 hours.

Locations

Country	Name	City	State
China	Gang Li	Shanghai	Shanghai

Sponsors (7)

Lead Sponsor	Collaborator
Shanghai East Hospital	Jinan Central Hospital, Ningbo No. 1 Hospital, Shanghai 6th People's Hospital, Shanghai 7th People's Hospital, Xuchang Central Hospital, Zhangzhou Municipal Hospital of Fujian Province

Country where clinical trial is conducted

China, 

References & Publications (14)

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. — View Citation

Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11. — View Citation

Guo Y, Lin Y, Tang Y, Tang Q, Wang X, Pan X, Zou J, Yang J. Safety and efficacy of early antiplatelet therapy in acute ischemic stroke patients receiving endovascular treatment: A systematic review and meta-analysis. J Clin Neurosci. 2019 Aug;66:45-50. doi: 10.1016/j.jocn.2019.05.028. Epub 2019 May 29. — View Citation

Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17. — View Citation

Kellert L, Hametner C, Rohde S, Bendszus M, Hacke W, Ringleb P, Stampfl S. Endovascular stroke therapy: tirofiban is associated with risk of fatal intracerebral hemorrhage and poor outcome. Stroke. 2013 May;44(5):1453-5. doi: 10.1161/STROKEAHA.111.000502. Epub 2013 Mar 5. — View Citation

Muniz-Lozano A, Rollini F, Franchi F, Angiolillo DJ. Update on platelet glycoprotein IIb/IIIa inhibitors: recommendations for clinical practice. Ther Adv Cardiovasc Dis. 2013 Aug;7(4):197-213. doi: 10.1177/1753944713487781. Epub 2013 Jul 1. — View Citation

Neuberger U, Seker F, Schonenberger S, Nagel S, Ringleb PA, Bendszus M, Pfaff JAR, Mohlenbruch MA. Prediction of intracranial hemorrhages after mechanical thrombectomy of basilar artery occlusion. J Neurointerv Surg. 2019 Dec;11(12):1181-1186. doi: 10.1136/neurintsurg-2019-014939. Epub 2019 Jun 1. — View Citation

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. — View Citation

Sun Y, Guo ZN, Yan X, Wang M, Zhang P, Qin H, Wang Y, Zhu H, Yang Y. Safety and efficacy of tirofiban combined with endovascular therapy compared with endovascular therapy alone in acute ischemic stroke: a meta-analysis. Neuroradiology. 2021 Jan;63(1):17-25. doi: 10.1007/s00234-020-02530-9. Epub 2020 Aug 25. — View Citation

Teng D, Pannell JS, Rennert RC, Li J, Li YS, Wong VW, Chien S, Khalessi AA. Endothelial trauma from mechanical thrombectomy in acute stroke: in vitro live-cell platform with animal validation. Stroke. 2015 Apr;46(4):1099-106. doi: 10.1161/STROKEAHA.114.007494. Epub 2015 Feb 24. — View Citation

Wu Y, Yin C, Yang J, Jiang L, Parsons MW, Lin L. Endovascular Thrombectomy. Stroke. 2018 Nov;49(11):2783-2785. doi: 10.1161/STROKEAHA.118.022919. — View Citation

Yang J, Wu Y, Gao X, Bivard A, Levi CR, Parsons MW, Lin L; INSPIRE Study Groupdagger. Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke. Stroke. 2020 Oct;51(10):2925-2933. doi: 10.1161/STROKEAHA.120.029994. Epub 2020 Sep 16. — View Citation

Yang M, Huo X, Gao F, Wang A, Ma N, Shi H, Chen W, Wang S, Wang Y, Miao Z. Low-dose rescue tirofiban in mechanical thrombectomy for acute cerebral large-artery occlusion. Eur J Neurol. 2020 Jun;27(6):1056-1061. doi: 10.1111/ene.14170. Epub 2020 Mar 17. — View Citation

Zhou J, Gao Y, Ma QL. Safety and efficacy of tirofiban in acute ischemic stroke patients not receiving endovascular treatment: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1492-1503. doi: 10.26355/eurrev_202002_20208. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite rates of target vessel revascularization and no symptomatic intracerebral haemorrhage	Target vessel revascularization is defined as a modified thrombolysis in cerebral infarction (mTICI) grade after onepass thrombectomy procedure over grade 2b. Symptomatic intracerebral haemorrhage is defined according to per Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria.	24-72hours after thrombectomy;
Secondary	Recanalisation rates of the target vessel	Neuroimaging outcomes	24-72 hours after thrombectomy;
Secondary	Dichotomized mRS score/ ordinal mRS score	Functional prognosis of the patient,clinical outcomes	The 90-day after randomisation
Secondary	Symptomatic intracerebral haemorrhage	procedure-related complications and adverse events	By the end of the 90-day follow-up
Secondary	Death	procedure-related complications and adverse events	By the end of the 90-day follow-up
Secondary	The number of thrombectomy times	Treatment information	By the end of the 90-day follow-up