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MOST: Multi-arm Optimization of Stroke Thrombolysis

Sponsor
Washington University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT03735979
Collaborator
National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
1,200
Enrollment
96
Locations
3
Arms
65.5
Anticipated Duration (Months)
12.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
Anticipated 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 :
Oct 15, 2019
Anticipated Primary Completion Date :
Nov 1, 2024
Anticipated Study Completion Date :
Apr 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. 90-day modified Rankin scores (mRS) [90 days after randomization]

Secondary Outcome Measures

  1. proportion of participants with NIHSS less than or equal to 2 at 24 hours [2 at 24 hours after randomization]

  2. change from baseline to 24-hour NIHSS [24 hours after randomization]

  3. proportion of participants with 90-day mRS 0-1 (or return to their historical mRS) [90 days after randomization]

  4. proportion of participants with 90-day mRS 0-2 (or return to their historical mRS) [90 days after randomization]

  5. 90-day ordinal analysis of the mRS [90 days after randomization]

  6. 90-day EQ-5D [90 days after randomization]

  7. proportion of participants who have thrombectomy [baseline]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. Example: known cirrhosis or clinically significant hepatic disease

  1. Current participation in another research drug treatment or interventional device trial - Subjects could not start another experimental agent until after 90 days

  2. Informed consent from the patient or the legally authorized representative was not or could not be obtained

  3. High density lesion consistent with hemorrhage of any degree

  4. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama Hospital Birmingham Alabama United States 35233
2 Community Regional Medical Center of Fresno Fresno California United States 93721
3 UCSD Health La Jolla La Jolla California United States 92037
4 Kaiser Permanente Los Angeles Medical Center Los Angeles California United States 90027
5 Cedars-Sinai Medical Center Los Angeles California United States 90048
6 Ronald Reagan UCLA Medical Center Los Angeles California United States 90095
7 UC Irvine Medical Center Orange California United States 92868
8 Desert Regional Medical Center Palm Springs California United States 92262
9 UCSD Medical Center - Hillcrest Hospital San Diego California United States 92103
10 San Francisco General Hospital San Francisco California United States 94110
11 UCSF Medical Center San Francisco California United States 94143
12 Santa Barbara Cottage Hospital Santa Barbara California United States 93105
13 Stanford University Medical Center Stanford California United States 94305
14 Harbor UCLA Medical Center Torrance California United States 90502
15 Swedish Medical Center Englewood Colorado United States 80113
16 Yale New Haven Hospital New Haven Connecticut United States 06510
17 UF Health Shands Hospital Gainesville Florida United States 32610
18 Baptist Medical Center Jacksonville Jacksonville Florida United States 32207
19 Mayo Clinic Hospital Jacksonville Florida United States 32224
20 Jackson Memorial Hospital Miami Florida United States 33136
21 Baptist Hospital of Miami Miami Florida United States 33176
22 Sarasota Memorial Hospital Sarasota Florida United States 34239
23 Tampa General Hospital Tampa Florida United States 33606
24 Grady Memorial Hospital Atlanta Georgia United States 30303
25 Rush University Medical Center Chicago Illinois United States 60612
26 University of Chicago Medical Center Chicago Illinois United States 60637
27 Loyola University Medical Center Maywood Illinois United States 60153
28 Central DuPage Hospital Winfield Illinois United States 60190
29 University of Iowa Hospitals & Clinics Iowa City Iowa United States 52242
30 University of Kansas Hospital Kansas City Kansas United States 66160
31 St. Elizabeth Medical Center South Edgewood Kentucky United States 41017
32 St. Elizabeth Hospital Florence Kentucky United States 41042
33 St. Elizabeth Hospital Fort Thomas Fort Thomas Kentucky United States 41075
34 University of Kentucky Hospital Lexington Kentucky United States 40536
35 University of Louisville Hospital Louisville Kentucky United States 40202
36 Ochsner Medical Center New Orleans Louisiana United States 70121
37 Massachusetts General Hospital Boston Massachusetts United States 02114
38 Boston Medical Center Boston Massachusetts United States 02118
39 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
40 UMASS Memorial Medical Center Worcester Massachusetts United States 01655
41 University of Michigan University Hospital Ann Arbor Michigan United States 48109
42 Henry Ford Hospital Detroit Michigan United States 48202
43 McLaren Flint Flint Michigan United States 48532
44 Mercy Health Saint Mary's Grand Rapids Michigan United States 49503
45 Fairview Southdale Hospital Edina Minnesota United States 55425
46 University of Minnesota Medical Center Hospital Minneapolis Minnesota United States 55455
47 Regions Hospital Saint Paul Minnesota United States 55101
48 University of Mississippi Medical Center Jackson Mississippi United States 39216
49 Saint Luke's Hospital Kansas City Missouri United States 64111
50 St. Louis University Hospital Saint Louis Missouri United States 63108
51 Barnes Jewish Hospital Saint Louis Missouri United States 63110
52 University of New Mexico Hospital Albuquerque New Mexico United States 87106
53 North Shore University Hospital Manhasset New York United States 11030
54 Mount Sinai Beth Israel New York New York United States 10003
55 The Mount Sinai Hospital New York New York United States 10029
56 NYP Columbia University Medical Center New York New York United States 10032
57 NYP Weill Cornell Medical Center New York New York United States 10065
58 Lenox Hill Hospital New York New York United States 10075
59 Strong Memorial Hospital Rochester New York United States 14642
60 SUNY Upstate University Hospital Syracuse New York United States 13210
61 Forsyth Medical Center Winston-Salem North Carolina United States 27103
62 Wake Forest Baptist Medical Center Winston-Salem North Carolina United States 27103
63 Akron General Medical Center Akron Ohio United States 44307
64 Mercy Health West Hospital Cincinnati Ohio United States 45211
65 Christ Hospital Cincinnati Ohio United States 45219
66 University of Cincinnati Medical Center Cincinnati Ohio United States 45219
67 Good Samaritan Hospital Cincinnati Ohio United States 45220
68 The Jewish Hospital Cincinnati Ohio United States 45236
69 Bethesda North Hospital Cincinnati Ohio United States 45242
70 Mercy Hospital Anderson Cincinnati Ohio United States 45255
71 OSU Wexner Medical Center Columbus Ohio United States 43210
72 Miami Valley Hospital Dayton Ohio United States 45409
73 Mercy Health Fairfield Hospital Fairfield Ohio United States 45014
74 St. John Medical Center Tulsa Oklahoma United States 74104
75 Abington Memorial Hospital Abington Pennsylvania United States 19001
76 St. Luke's University Hospital Bethlehem Pennsylvania United States 18015
77 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
78 Temple University Hospital Philadelphia Pennsylvania United States 19140
79 UPMC Presbyterian Hospital Pittsburgh Pennsylvania United States 15213
80 UPMC Mercy Hospital Pittsburgh Pennsylvania United States 15219
81 WellSpan York Hospital York Pennsylvania United States 17403
82 Rhode Island Hospital Providence Rhode Island United States 02903
83 Medical University of South Carolina Charleston South Carolina United States 29425
84 Greenville Hospital System Greenville South Carolina United States 29605
85 Vanderbilt University Hospital Nashville Tennessee United States 37232
86 Baylor University Medical Center Dallas Texas United States 75246
87 DHR Health Edinburg Texas United States 78539
88 Valley Baptist Medical Center Harlingen Texas United States 78550
89 Houston Methodist Hospital Houston Texas United States 77030
90 Memorial Hermann-Texas Medical Center Houston Texas United States 77030
91 South Texas Health System McAllen McAllen Texas United States 78503
92 Houston Methodist The Woodlands Hospital The Woodlands Texas United States 77385
93 University of Utah Health Salt Lake City Utah United States 84132
94 UVA Medical Center Charlottesville Virginia United States 22908
95 WVU Healthcare Ruby Memorial Hospital Morgantown West Virginia United States 26506
96 University of Wisconsin University Hospital Madison Wisconsin United States 53792

Sponsors and Collaborators

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

Investigators

  • Principal Investigator: Opeolu Adeoye, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
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
First Posted:
Nov 8, 2018
Last Update Posted:
Jun 7, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Stroke
Ischemic Stroke
Argatroban
Eptifibatide

Study Results

No Results Posted as of Jun 7, 2022