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Multi-arm Optimization of Stroke Thrombolysis (MOST)

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ClinicalTrials.gov Identifier: NCT03735979
Recruitment Status : Recruiting
First Posted : November 8, 2018
Last Update Posted : August 3, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Opeolu Makanju Adeoye, Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Drug: Argatroban Drug: Eptifibatide Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-arm Optimization of Stroke Thrombolysis (MOST): a Single Blinded, Randomized Controlled Adaptive, Multi-arm, Adjunctive-thrombolysis Efficacy Trial in Ischemic Stroke
Actual Study Start Date : October 15, 2019
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Placebo Comparator: Placebo Drug: Placebo
IV placebo solution




Primary Outcome Measures :
  1. 90-day modified Rankin scores (mRS) [ Time Frame: 90 days after randomization ]

Secondary Outcome Measures :
  1. proportion of participants with NIHSS less than or equal to 2 at 24 hours [ Time Frame: 2 at 24 hours after randomization ]
  2. change from baseline to 24-hour NIHSS [ Time Frame: 24 hours after randomization ]
  3. proportion of participants with 90-day mRS 0-1 (or return to their historical mRS) [ Time Frame: 90 days after randomization ]
  4. proportion of participants with 90-day mRS 0-2 (or return to their historical mRS) [ Time Frame: 90 days after randomization ]
  5. 90-day ordinal analysis of the mRS [ Time Frame: 90 days after randomization ]
  6. 90-day EQ-5D [ Time Frame: 90 days after randomization ]
  7. proportion of participants who have thrombectomy [ Time Frame: baseline ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03735979


Contacts
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Contact: Opeolu Adeoye, MD 314-747-4156 adeoye@wustl.edu
Contact: Andrew Barreto, MD 713-500-7002 Andrew.d.barreto@uth.tmc.edu

Locations
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Sponsors and Collaborators
Washington University School of Medicine
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Opeolu Adeoye, MD Washington University School of Medicine
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Opeolu Makanju Adeoye, Professor and Chair, Department of Emergency Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03735979    
Other Study ID Numbers: 2018-1464
1U01NS100699-01A1 ( U.S. NIH Grant/Contract )
First Posted: November 8, 2018    Key Record Dates
Last Update Posted: August 3, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Argatroban
Eptifibatide
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Platelet Aggregation Inhibitors