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Acute Ischemic StrokePhase 3MOSTNCT03735979

Multi-arm Optimization of Stroke Thrombolysis

A Phase 3 study testing Argatroban and Eptifibatide in people with Acute Ischemic Stroke, run by Washington University School of Medicine at 61 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Ischemic Stroke
What is being tested?
Argatroban and Eptifibatide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
514 participants
Where
61 sitesUnited States
Study dates
15 Oct 2019to 31 Oct 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 29Show fewer
  • 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 %
  • Elevated pre-thrombolysis PTT above laboratory upper limit of normal
  • Creatinine > 4 mg/dl
  • Ongoing renal dialysis, regardless of creatinine
  • Received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) in full dose within the previous 24 hours
  • Abnormal PTT within 48 hours prior to randomization after receiving heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, dabigatran or lepirudin)
  • Received Factor Xa inhibitors (such as Fondaparinaux, apixaban or rivaroxaban) within the past 48 hours
  • Received glycoprotein IIb/IIIa inhibitors within the past 14 days
  • Pre-existing neurological or psychiatric disease which confounded the neurological or functional evaluations e.g., baseline modified Rankin score >3
  • 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
  • Example: known cirrhosis or clinically significant hepatic disease
  • Current participation in another research drug treatment or interventional device trial - Subjects could not start another experimental agent until after 90 days
  • Informed consent from the patient or the legally authorized representative was not or could not be obtained
  • High density lesion consistent with hemorrhage of any degree
  • 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

Trial locations and contacts

61 sites in 1 country.

61 sites in 1 country

United States61 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • University of New Mexico Hospital

    Albuquerque, New Mexico, 87106

  • University of Michigan University Hospital

    Ann Arbor, Michigan, 48109

  • Grady Memorial Hospital

    Atlanta, Georgia, 30303

  • University of Alabama Hospital

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • UVA Medical Center

    Charlottesville, Virginia, 22908

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Mercy Health West Hospital

    Cincinnati, Ohio, 45211

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • The Jewish Hospital

    Cincinnati, Ohio, 45236

  • OSU Wexner Medical Center

    Columbus, Ohio, 43210

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Fairview Southdale Hospital

    Edina, Minnesota, 55425

  • McLaren Flint

    Flint, Michigan, 48532

  • St. Jude Medical Center

    Fullerton, California, 92835

  • Trinity Health Saint Mary's

    Grand Rapids, Michigan, 49503

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • Memorial Hermann-Texas Medical Center

    Houston, Texas, 77030

  • Baptist Medical Center Jacksonville

    Jacksonville, Florida, 32207

  • Mayo Clinic Hospital

    Jacksonville, Florida, 32224

  • University of Kansas Hospital

    Kansas City, Kansas, 66160

  • Saint Luke's Hospital

    Kansas City, Missouri, 64111

  • UCSD Health La Jolla

    La Jolla, California, 92037

  • University of Kentucky Hospital

    Lexington, Kentucky, 40536

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • South Texas Health System McAllen

    McAllen, Texas, 78503

  • Jackson Memorial Hospital

    Miami, Florida, 33136

  • University of Minnesota Medical Center Hospital

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Hospital

    Nashville, Tennessee, 37232

  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

  • Mount Sinai Beth Israel

    New York, New York, 10003

  • UC Irvine Medical Center

    Orange, California, 92868

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • UPMC Presbyterian Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC Mercy Hospital

    Pittsburgh, Pennsylvania, 15219

  • Javon Bea Hospital - Riverside

    Rockford, Illinois, 61114

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • University of Utah Healthcare

    Salt Lake City, Utah, 84132

  • UCSD Medical Center - Hillcrest Hospital

    San Diego, California, 92103

  • San Francisco General Hospital

    San Francisco, California, 94110

  • UCSF Medical Center

    San Francisco, California, 94143

  • Santa Barbara Cottage Hospital

    Santa Barbara, California, 93105

  • Sarasota Memorial Hospital

    Sarasota, Florida, 34239

  • St. Louis University Hospital

    St Louis, Missouri, 63108

  • Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • SUNY Upstate University Hospital

    Syracuse, New York, 13210

  • Tampa General Hospital

    Tampa, Florida, 33606

  • St. John Medical Center

    Tulsa, Oklahoma, 74104

  • Central DuPage Hospital

    Winfield, Illinois, 60190

  • Forsyth Medical Center

    Winston-Salem, North Carolina, 27103

  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27103

  • UMASS Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: 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.

Being tested
Argatroban, Eptifibatide, Placebo
Medical subject headings
Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ArgatrobanDrug

    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.

  • EptifibatideDrug

    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.

  • PlaceboDrug

    IV placebo solution

Study groups in NCT03735979
Study groupRoleWhat they receive
ArgatrobanExperimental100µg/kg bolus followed by 3µg/kg per minute for 12 hours
Receives: Drug: Argatroban
EptifibatideExperimental135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours
Receives: Drug: Eptifibatide
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 90 days after randomization

Secondary outcomes (8)

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

    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.

    Measured: 24 hours after randomization

  2. Change From Baseline to 24-hour NIHSS

    National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit.

    Measured: 24 hours after randomization

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

    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.

    Measured: 90 days after randomization

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

    modified Rankin scale is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes.

    Measured: 90 days after randomization

  5. 90-day mRS

    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.

    Measured: 90 days after randomization

  6. 90-day EQ-5D

    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.

    Measured: 90 days after randomization

  7. Pre-thrombectomy Modified TICI Score of 2B.

    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.

    Measured: baseline

  8. Post-thrombectomy Modified TICI Score of 2B or 3

    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

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2018
  2. Study start15 Oct 2019
  3. Primary completion1 Dec 2023
  4. Study completion31 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
514 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03735979
Sponsor's protocol ID
2018-1464
Other IDs
1U01NS100699-01A1
Acronym
MOST
Status last verified
Jan 2025
First submitted
7 Nov 2018
Last updated
7 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 41071964

  • 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.

    PubMed 40824660

  • 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.

    PubMed 40123511

  • 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.

    PubMed 39231343

  • 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.

    PubMed 37256980

  • 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.

    PubMed 33297893

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Argatroban and Eptifibatide in people with Acute Ischemic Stroke, run by Washington University School of Medicine at 61 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

90-day Utility Weighted Modified Rankin Scores (UW-mRS) (time frame: 90 days after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03735979, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2025; AzTrials last refreshed its copy on 30 Oct 2026.

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