Multi-arm Optimization of Stroke Thrombolysis

NCT03735979 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2018-14641U01NS100699-01A1
• Study Type: interventional
• Target: 514
• Locations: 1 country
• Sites: 61

Brief 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.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• 90-day Utility Weighted Modified Rankin Scores (UW-mRS)

  The modified Rankin scale is a 7 point ordinal scale ranging from 0="no symptoms" to 6="death" . For the primary analysis, the scale was analyzed with patient-centered utility weights. We assigned the following utility weights to the seven levels: 10, 9.1,, 7.6, 6.5, 3.3, 0, 0 (with higher scores indicating a better outcome).

  90 days after randomization

Secondary Outcomes (8)

• Percentage of Participants With NIHSS Less Than or Equal to 2 at 24 Hours

  24 hours after randomization

• Change From Baseline to 24-hour NIHSS

  24 hours after randomization

• Percentage of Participants With 90-day mRS 0 or 1 (or Return to Their Historical mRS)

  90 days after randomization

• Percentage of Participants With 90-day mRS 0, 1 or 2 (or Return to Their Historical mRS)

  90 days after randomization

• 90-day mRS

  90 days after randomization

Other Outcomes (4)

• Symptomatic Intracranial Hemorrhage Within 36 Hours (Primary Safety Outcome)

  36 hours after randomization

• Type 1 or Type 2 Parenchymal Hemorrhage Within 36 Hours (Safety Outcome)

  36 hours after randomization

• Any Intracranial Hemorrhage Within 36 Hours (Safety Outcome)

  36 hours after randomization

Study Arms (3)

Argatroban

EXPERIMENTAL

100µg/kg bolus followed by 3µg/kg per minute for 12 hours

Drug: Argatroban

Eptifibatide

EXPERIMENTAL

135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours

Drug: Eptifibatide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Argatroban DRUG

Direct Thrombin Inhibitor - Argatroban is a derivative of arginine that competitively binds to the active site of thrombin thereby preventing fibrin deposition. With a half-life of 30 minutes, argatroban has an immediate anticoagulant effect after IV administration which is rapidly reversed with discontinuation of the drug.

Argatroban

Eptifibatide DRUG

GP 2b/3a Receptor Inhibitor - The final step of platelet aggregation is mediated via the GP2b/3a receptor. Eptifibatide was specifically developed to ensure rapid inhibition of platelet aggregation (within 15 minutes), a short half-life (\~2 hours) and rapid dissociation from platelets with 50% restoration of platelet function within 2-4 hours of discontinuation.

Eptifibatide

Placebo DRUG

IV placebo solution

Placebo

Eligibility Criteria

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

You may qualify if:

• Acute ischemic stroke patients
• Treated with 0.9mg/kg IV rt-PA or 0.25mg/kg IV TNK within 3 hours of stroke onset or time last known well
• Age ≥ 18
• NIHSS score ≥ 6 prior to IV thrombolysis
• Able to receive assigned study drug within 60 minutes but no later than 75 minutes of initiation of IV thrombolysis

You may not qualify if:

• Known allergy or hypersensitivity to argatroban or eptifibatide
• Previous stroke in the past 90 days
• Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation
• Clinical presentation suggested a subarachnoid hemorrhage, even if initial CT scan was normal
• Any surgery, or biopsy of parenchymal organ in the past 30 days
• Trauma with internal injuries or ulcerative wounds in the past 30 days
• Severe head trauma in the past 90 days
• Systolic blood pressure persistently \>180mmHg post-IV thrombolysis despite antihypertensive intervention
• Diastolic blood pressure persistently \>105mmHg post-IV thrombolysis despite antihypertensive intervention
• Serious systemic hemorrhage in the past 30 days
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \>1.5
• Positive urine or serum pregnancy test for women of child bearing potential
• Glucose \<50 or \>400 mg/dl
• Platelets \<100,000/mm3
• Hematocrit \<25 %

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (61)

University of Alabama Hospital

Birmingham, Alabama, 35233, United States

Location

St. Jude Medical Center

Fullerton, California, 92835, United States

Location

UCSD Health La Jolla

La Jolla, California, 92037, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

UCSD Medical Center - Hillcrest Hospital

San Diego, California, 92103, United States

Location

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Santa Barbara Cottage Hospital

Santa Barbara, California, 93105, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Baptist Medical Center Jacksonville

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Javon Bea Hospital - Riverside

Rockford, Illinois, 61114, United States

Location

Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

University of Kentucky Hospital

Lexington, Kentucky, 40536, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

UMASS Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan University Hospital

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

McLaren Flint

Flint, Michigan, 48532, United States

Location

Trinity Health Saint Mary's

Grand Rapids, Michigan, 49503, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55425, United States

Location

University of Minnesota Medical Center Hospital

Minneapolis, Minnesota, 55455, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

St. Louis University Hospital

St Louis, Missouri, 63108, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

SUNY Upstate University Hospital

Syracuse, New York, 13210, United States

Location

Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Cleveland Clinic Akron General

Akron, Ohio, 44307, United States

Location

Mercy Health West Hospital

Cincinnati, Ohio, 45211, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

The Jewish Hospital

Cincinnati, Ohio, 45236, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

St. John Medical Center

Tulsa, Oklahoma, 74104, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prisma Health Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

Location

Vanderbilt University Hospital

Nashville, Tennessee, 37232, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Memorial Hermann-Texas Medical Center

Houston, Texas, 77030, United States

Location

South Texas Health System McAllen

McAllen, Texas, 78503, United States

Location

University of Utah Healthcare

Salt Lake City, Utah, 84132, United States

Location

UVA Medical Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (6)

• 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.

  PMID: 41071964 DERIVED

• 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.

  PMID: 40824660 DERIVED

• 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.

  PMID: 40123511 DERIVED

• 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.

  PMID: 39231343 DERIVED

• 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.

  PMID: 37256980 DERIVED

• 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.

  PMID: 33297893 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

argatroban; Eptifibatide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Jordan J. Elm, PhD
• Organization: Medical University of South Carolina

elmj@musc.edu

843-876-1605

Study Officials

• Opeolu Adeoye, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Emergency Medicine

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 8, 2018
• Study Start: October 15, 2019
• Primary Completion: December 1, 2023
• Study Completion: October 31, 2024
• Last Updated: February 7, 2025
• Results First Posted: November 19, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (61)