Multi-arm Optimization of Stroke Thrombolysis

Acute Ischemic Stroke Clinical Trial

— MOST  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03735979
• Other study ID #: 2018-1464
• Secondary ID: 1U01NS100699-01A
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 15, 2019
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 514
• Est. completion date: April 2025
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemic Stroke
• Stroke

Intervention

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.
• 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
IV placebo solution

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	University of New Mexico Hospital	Albuquerque	New Mexico
United States	University of Michigan University Hospital	Ann Arbor	Michigan
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	University of Alabama Hospital	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	UVA Medical Center	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Mercy Health West Hospital	Cincinnati	Ohio
United States	The Jewish Hospital	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	McLaren Flint	Flint	Michigan
United States	St. Jude Medical Center	Fullerton	California
United States	Trinity Health Saint Mary's	Grand Rapids	Michigan
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Houston Methodist Hospital	Houston	Texas
United States	Memorial Hermann-Texas Medical Center	Houston	Texas
United States	Baptist Medical Center Jacksonville	Jacksonville	Florida
United States	Mayo Clinic Hospital	Jacksonville	Florida
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	University of Kansas Hospital	Kansas City	Kansas
United States	UCSD Health La Jolla	La Jolla	California
United States	University of Kentucky Hospital	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	South Texas Health System McAllen	McAllen	Texas
United States	Jackson Memorial Hospital	Miami	Florida
United States	University of Minnesota Medical Center Hospital	Minneapolis	Minnesota
United States	Vanderbilt University Hospital	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Mount Sinai Beth Israel	New York	New York
United States	UC Irvine Medical Center	Orange	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	UPMC Mercy Hospital	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Javon Bea Hospital - Riverside	Rockford	Illinois
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	St. Louis University Hospital	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	San Francisco General Hospital	San Francisco	California
United States	UCSF Medical Center	San Francisco	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	SUNY Upstate University Hospital	Syracuse	New York
United States	Tampa General Hospital	Tampa	Florida
United States	St. John Medical Center	Tulsa	Oklahoma
United States	Central DuPage Hospital	Winfield	Illinois
United States	Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90-day modified Rankin scores (mRS)		90 days after randomization
Secondary	proportion of participants with NIHSS less than or equal to 2 at 24 hours		2 at 24 hours after randomization
Secondary	change from baseline to 24-hour NIHSS		24 hours after randomization
Secondary	proportion of participants with 90-day mRS 0-1 (or return to their historical mRS)		90 days after randomization
Secondary	proportion of participants with 90-day mRS 0-2 (or return to their historical mRS)		90 days after randomization
Secondary	90-day ordinal analysis of the mRS		90 days after randomization
Secondary	90-day EQ-5D		90 days after randomization
Secondary	proportion of participants who have thrombectomy		baseline