Multi-arm Optimization of Stroke Thrombolysis (MOST)

January 23, 2025 updated by: Opeolu Makanju Adeoye, Washington University School of Medicine

Multi-arm Optimization of Stroke Thrombolysis (MOST): a Single Blinded, Randomized Controlled Adaptive, Multi-arm, Adjunctive-thrombolysis Efficacy Trial in Ischemic Stroke

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
514

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama Hospital
    • California
      • Fullerton, California, United States, 92835
        • St. Jude Medical Center
      • La Jolla, California, United States, 92037
        • UCSD Health La Jolla
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Orange, California, United States, 92868
        • UC Irvine Medical Center
      • San Diego, California, United States, 92103
        • UCSD Medical Center - Hillcrest Hospital
      • San Francisco, California, United States, 94110
        • San Francisco General Hospital
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
      • Santa Barbara, California, United States, 93105
        • Santa Barbara Cottage Hospital
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Hospital
      • Jacksonville, Florida, United States, 32207
        • Baptist Medical Center Jacksonville
      • Miami, Florida, United States, 33136
        • Jackson Memorial Hospital
      • Sarasota, Florida, United States, 34239
        • Sarasota Memorial Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Grady Memorial Hospital
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University Of Chicago Medical Center
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Rockford, Illinois, United States, 61114
        • Javon Bea Hospital - Riverside
      • Winfield, Illinois, United States, 60190
        • Central DuPage Hospital
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Hospital
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan University Hospital
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Flint, Michigan, United States, 48532
        • McLaren Flint
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Saint Mary's
    • Minnesota
      • Edina, Minnesota, United States, 55425
        • Fairview Southdale Hospital
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital
      • Saint Louis, Missouri, United States, 63110
        • Barnes Jewish Hospital
      • Saint Louis, Missouri, United States, 63108
        • St. Louis University Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Hospital
    • New York
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10003
        • Mount Sinai Beth Israel
      • Syracuse, New York, United States, 13210
        • SUNY Upstate University Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Wake Forest Baptist Medical Center
      • Winston-Salem, North Carolina, United States, 27103
        • Forsyth Medical Center
    • Ohio
      • Akron, Ohio, United States, 44307
        • Cleveland Clinic Akron General
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
      • Cincinnati, Ohio, United States, 45236
        • The Jewish Hospital
      • Cincinnati, Ohio, United States, 45211
        • Mercy Health West Hospital
      • Columbus, Ohio, United States, 43210
        • OSU Wexner Medical Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
        • St. John Medical Center
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Presbyterian Hospital
      • Pittsburgh, Pennsylvania, United States, 15219
        • UPMC Mercy Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Greenville Memorial Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • Memorial Hermann-Texas Medical Center
      • McAllen, Texas, United States, 78503
        • South Texas Health System McAllen
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Healthcare
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • UVA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Acute ischemic stroke patients
  2. 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
  3. Age ≥ 18
  4. NIHSS score ≥ 6 prior to IV thrombolysis
  5. Able to receive assigned study drug within 60 minutes but no later than 75 minutes of initiation of IV thrombolysis

Exclusion Criteria:

  1. Known allergy or hypersensitivity to argatroban or eptifibatide
  2. Previous stroke in the past 90 days
  3. Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation
  4. Clinical presentation suggested a subarachnoid hemorrhage, even if initial CT scan was normal
  5. Any surgery, or biopsy of parenchymal organ in the past 30 days
  6. Trauma with internal injuries or ulcerative wounds in the past 30 days
  7. Severe head trauma in the past 90 days
  8. Systolic blood pressure persistently >180mmHg post-IV thrombolysis despite antihypertensive intervention
  9. Diastolic blood pressure persistently >105mmHg post-IV thrombolysis despite antihypertensive intervention
  10. Serious systemic hemorrhage in the past 30 days
  11. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >1.5
  12. Positive urine or serum pregnancy test for women of child bearing potential
  13. Glucose <50 or >400 mg/dl
  14. Platelets <100,000/mm3
  15. Hematocrit <25 %
  16. Elevated pre-thrombolysis PTT above laboratory upper limit of normal
  17. Creatinine > 4 mg/dl
  18. Ongoing renal dialysis, regardless of creatinine
  19. Received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) in full dose within the previous 24 hours
  20. Abnormal PTT within 48 hours prior to randomization after receiving heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, dabigatran or lepirudin)
  21. Received Factor Xa inhibitors (such as Fondaparinaux, apixaban or rivaroxaban) within the past 48 hours
  22. Received glycoprotein IIb/IIIa inhibitors within the past 14 days
  23. Pre-existing neurological or psychiatric disease which confounded the neurological or functional evaluations e.g., baseline modified Rankin score >3

  24. Other serious, advanced, or terminal illness or any other condition that the investigator felt would pose a significant hazard to the patient if rt-PA, TNK, eptifibatide or argatroban therapy was initiated

    a. Example: known cirrhosis or clinically significant hepatic disease

  25. Current participation in another research drug treatment or interventional device trial - Subjects could not start another experimental agent until after 90 days
  26. Informed consent from the patient or the legally authorized representative was not or could not be obtained
  27. High density lesion consistent with hemorrhage of any degree
  28. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT Scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo
IV placebo solution
Experimental: Argatroban
100µg/kg bolus followed by 3µg/kg per minute for 12 hours
Drug: Argatroban
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.
Experimental: Eptifibatide
135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours
Drug: Eptifibatide
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
90-day Utility Weighted Modified Rankin Scores (UW-mRS)
Time Frame: 90 days after randomization
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With NIHSS Less Than or Equal to 2 at 24 Hours
Time Frame: 24 hours after randomization
National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit. This is a dichotomous analysis with a cutpoint of 0,1,2 defining the event.
24 hours after randomization
Change From Baseline to 24-hour NIHSS
Time Frame: 24 hours after randomization
National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit.
24 hours after randomization
Percentage of Participants With 90-day mRS 0 or 1 (or Return to Their Historical mRS)
Time Frame: 90 days after randomization
The modified Rankin scale (mRS) is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes. For patients with a pre-stroke mRS of greater than 0 or 1, these patients had to return to their historical (pre-stroke) value to be counted as a success.
90 days after randomization
Percentage of Participants With 90-day mRS 0, 1 or 2 (or Return to Their Historical mRS)
Time Frame: 90 days after randomization
modified Rankin scale is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes.
90 days after randomization
90-day mRS
Time Frame: 90 days after randomization
modified Rankin scale is a 7 point ordinal scale ranging from 0="no symptoms at all" to 6="death" where lower scores are better outcomes.
90 days after randomization
90-day EQ-5D
Time Frame: 90 days after randomization
EuroQol Five-Dimension (EQ-5D) is a measure of health-related quality of life ranging from -0.59 to 1 where 1 is the best possible health state.
90 days after randomization
Pre-thrombectomy Modified TICI Score of 2B.
Time Frame: baseline
The modified thrombolysis in cerebral infarction (TICI) score prior to endovascular thrombectomy procedure. The modified pre-thrombectomy TICI score is a 4 point scale with possible values of 0, 1, 2A, and 2B. The values are defined as follows: 0=No flow, 1=Penetration without distal branch filling, 2A=<50% partial reperfusion, and 2B=50%-99% partial reperfusion.
baseline
Post-thrombectomy Modified TICI Score of 2B or 3
Time Frame: baseline
The modified thrombolysis in cerebral infarction (TICI) score prior to endovascular thrombectomy procedure. The modified post-thrombectomy TICI score is a 5 point scale with possible values of 0, 1, 2A, 2B, 3. The values are defined as follows: 0=No flow, 1=Penetration without distal branch filling, 2A=<50% partial reperfusion, 2B=50%-99% partial reperfusion, and 3=Completed reperfusion
baseline

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Symptomatic Intracranial Hemorrhage Within 36 Hours (Primary Safety Outcome)
Time Frame: 36 hours after randomization
Type 2 parenchymal hemorrhage or a parenchymal hemorrhage remote from the area of infarction with neurologic deterioration (defined as an increase of ≥4 points in the NIHSS score)within 36 hours after randomization.
36 hours after randomization
Type 1 or Type 2 Parenchymal Hemorrhage Within 36 Hours (Safety Outcome)
Time Frame: 36 hours after randomization
36 hours after randomization
Any Intracranial Hemorrhage Within 36 Hours (Safety Outcome)
Time Frame: 36 hours after randomization
Symptomatic or asymptomatic intracranial hemorrhage within 36 hours of randomization.
36 hours after randomization
Other Major Hemorrhage Other Than Intracranial Hemorrhage Within 7 Days (Safety Outcome)
Time Frame: 7 days after randomization
Other major hemorrhage other than intracranial hemorrhage (resulting in the transfusion of >2 units of packed red cells).
7 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Opeolu Adeoye, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 15, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 8, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2018-1464
  • 1U01NS100699-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings