Clinical trial NCT03735979: Multi-arm Optimization of Stroke Thrombolysis
Official title: Multi-arm Optimization of Stroke Thrombolysis (MOST): a Single Blinded, Randomized Controlled Adaptive, Multi-arm, Adjunctive-thrombolysis Efficacy Trial in Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2018-11-08
Enrollment: 514
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 90-day Utility Weighted Modified Rankin Scores (UW-mRS)
timeFrame: 90 days after randomization
Secondary outcomes:
measure: Percentage of Participants With NIHSS Less Than or Equal to 2 at 24 Hours
timeFrame: 24 hours after randomization
measure: Change From Baseline to 24-hour NIHSS
timeFrame: 24 hours after randomization
measure: Percentage of Participants With 90-day mRS 0 or 1 (or Return to Their Historical mRS)
timeFrame: 90 days after randomization
measure: Percentage of Participants With 90-day mRS 0, 1 or 2 (or Return to Their Historical mRS)
timeFrame: 90 days after randomization
measure: 90-day mRS
timeFrame: 90 days after randomization
measure: 90-day EQ-5D
timeFrame: 90 days after randomization
measure: Pre-thrombectomy Modified TICI Score of 2B.
timeFrame: baseline
measure: Post-thrombectomy Modified TICI Score of 2B or 3
timeFrame: baseline
Other outcomes:
measure: Symptomatic Intracranial Hemorrhage Within 36 Hours (Primary Safety Outcome)
timeFrame: 36 hours after randomization
measure: Type 1 or Type 2 Parenchymal Hemorrhage Within 36 Hours (Safety Outcome)
timeFrame: 36 hours after randomization
measure: Any Intracranial Hemorrhage Within 36 Hours (Safety Outcome)
timeFrame: 36 hours after randomization
measure: Other Major Hemorrhage Other Than Intracranial Hemorrhage Within 7 Days (Safety Outcome)
timeFrame: 7 days after randomization
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital
state: Alabama
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: La Jolla
country: United States
facility: UCSD Health La Jolla
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center - Hillcrest Hospital
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist Medical Center Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Rockford
country: United States
facility: Javon Bea Hospital - Riverside
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Hospital
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan University Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: McLaren Flint
state: Michigan
city: Grand Rapids
country: United States
facility: Trinity Health Saint Mary's
state: Michigan
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate University Hospital
state: New York
city: Winston-Salem
country: United States
facility: Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Cleveland Clinic Akron General
state: Ohio
city: Cincinnati
country: United States
facility: Mercy Health West Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: The Jewish Hospital
state: Ohio
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Tulsa
country: United States
facility: St. John Medical Center
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Mercy Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Greenville Memorial Hospital
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Hospital
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann-Texas Medical Center
state: Texas
city: McAllen
country: United States
facility: South Texas Health System McAllen
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Healthcare
state: Utah
city: Charlottesville
country: United States
facility: UVA Medical Center
state: Virginia
Study officials:
affiliation: Washington University School of Medicine
name: Opeolu Adeoye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.