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 0.9mg/kg IV rt-PA 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.



Eligible Ages
Over 18 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  1. Acute ischemic stroke patients
  2. Treated with 0.9mg/kg IV rt-PA within 3 hours of stroke onset or time last known well
  3. Age ≥ 18
  4. NIHSS score ≥ 6 prior to IV rt-PA
  5. Able to receive assigned study drug within 60 minutes of initiation of IV rt-PA

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. 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 >180mmHg post-IV rt-PA
  9. Diastolic blood pressure >105mmHg post-IV rt-PA
  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 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 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, eptifibatide or argatroban therapy was initiated

a. Example: known cirrhosis or clinically significant hepatic disease

25. Current participation in another research drug treatment protocol - 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 Design

Phase 3
Study Type
Intervention Model
Parallel Assignment
Primary Purpose
Double (Participant, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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.
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.
Placebo Comparator
  • Drug: Placebo
    IV placebo solution

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky Hospital
Lexington, Kentucky 40536
Creed Pettigrew, MD

More Details

University of Cincinnati

Study Contact

Opeolu Adeoye, MD


Study information shown on this site is derived from (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.