Multi-arm Optimization of Stroke Thrombolysis

Summary

The primary efficacy objective of the MOST trial is to determine if argatroban (100µg/kg bolus followed by 3µg/kg per minute for 12 hours) or eptifibatide (135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours) results in improved 90-day modified Rankin scores (mRS) as compared with placebo in acute ischemic stroke (AIS) patients treated with standard of care thrombolysis (0.9mg/kg IV rt-PA or 0.25mg/kg IV tenecteplase or TNK) within three hours of symptom onset. Patients may also receive endovascular thrombectomy (ET) per usual care. Time of onset is defined as the last time the patient was last known to be well.

Timeline

Start

2019-10-15

Primary completion

2023-12-01

Completion

2024-10-31

Publications

• Roy A, Elm J, Ingles JR, Sabagha N, Huang JF, Bentho O, Ranasinghe T, Streib C, Concha M, Khatri P, Vagal A, Wintermark M, Derdeyn CP, Broderick JP, Barreto AD, Adeoye O, Grotta JC. Thrombolysis Alone vs With Argatroban or Eptifibatide: A Prespecified Subgroup Analysis of the MOST Trial. Neurology. 2025 Nov 11;105(9):e214228. doi: 10.1212/WNL.0000000000214228. Epub 2025 Oct 10.
• Rines I, Adeoye O, Barreto AD, Broderick J, Carrozzella J, Chen H, Concha M, Elm J, Grotta JC, Jasne AS, Khatri P, Roy A, Vagal A, Wintermark M, Yoo AJ, Derdeyn CP; MOST Investigators. Intravenous Argatroban or Eptifibatide in Patients Undergoing Mechanical Thrombectomy: A Subgroup Analysis of the MOST Randomized Clinical Trial. JAMA Neurol. 2025 Aug 18;82(10):1004-12. doi: 10.1001/jamaneurol.2025.2794. Online ahead of print.
• Shawkat A, Barreto AD, Broderick JP, Derdeyn CP, Grotta JC, Khatri P, Pizzella S, Rines I, Roy A, Wilson A, Wintermark M, Adeoye OM. Comparison of Local and Centrally Adjudicated Modified Rankin Scale Scores in the MOST Trial. Stroke. 2025 May;56(5):1280-1284. doi: 10.1161/STROKEAHA.124.049825. Epub 2025 Mar 24.
• Adeoye O, Broderick J, Derdeyn CP, Grotta JC, Barsan W, Bentho O, Berry S, Concha M, Davis I, Demel S, Elm J, Gentile N, Graves T, Hoffman M, Huang J, Ingles J, Janis S, Jasne AS, Khatri P, Levine SR, Majjhoo A, Panagos P, Pancioli A, Pizzella S, Ranasinghe T, Sabagha N, Sivakumar S, Streib C, Vagal A, Wilson A, Wintermark M, Yoo AJ, Barreto AD. Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke. N Engl J Med. 2024 Sep 5;391(9):810-820. doi: 10.1056/NEJMoa2314779.
• Romano JG, Rundek T. Expanding Treatment for Acute Ischemic Stroke beyond Revascularization. N Engl J Med. 2023 Jun 1;388(22):2095-2096. doi: 10.1056/NEJMe2303184. No abstract available.
• Deeds SI, Barreto A, Elm J, Derdeyn CP, Berry S, Khatri P, Moy C, Janis S, Broderick J, Grotta J, Adeoye O. The multiarm optimization of stroke thrombolysis phase 3 acute stroke randomized clinical trial: Rationale and methods. Int J Stroke. 2021 Oct;16(7):873-880. doi: 10.1177/1747493020978345. Epub 2020 Dec 9.

Drugs

Indications