Multi-arm Optimization of Stroke Thrombolysis
- Conditions
- Acute Ischemic Stroke
- Interventions
- Registration Number
- NCT03735979
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 514
- Acute ischemic stroke patients
- 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
- Age ≥ 18
- NIHSS score ≥ 6 prior to IV thrombolysis
- Able to receive assigned study drug within 60 minutes but no later than 75 minutes of initiation of IV thrombolysis
-
Known allergy or hypersensitivity to argatroban or eptifibatide
-
Previous stroke in the past 90 days
-
Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation
-
Clinical presentation suggested a subarachnoid hemorrhage, even if initial CT scan was normal
-
Any surgery, or biopsy of parenchymal organ in the past 30 days
-
Trauma with internal injuries or ulcerative wounds in the past 30 days
-
Severe head trauma in the past 90 days
-
Systolic blood pressure persistently >180mmHg post-IV thrombolysis despite antihypertensive intervention
-
Diastolic blood pressure persistently >105mmHg post-IV thrombolysis despite antihypertensive intervention
-
Serious systemic hemorrhage in the past 30 days
-
Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >1.5
-
Positive urine or serum pregnancy test for women of child bearing potential
-
Glucose <50 or >400 mg/dl
-
Platelets <100,000/mm3
-
Hematocrit <25 %
-
Elevated pre-thrombolysis PTT above laboratory upper limit of normal
-
Creatinine > 4 mg/dl
-
Ongoing renal dialysis, regardless of creatinine
-
Received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) in full dose within the previous 24 hours
-
Abnormal PTT within 48 hours prior to randomization after receiving heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, dabigatran or lepirudin)
-
Received Factor Xa inhibitors (such as Fondaparinaux, apixaban or rivaroxaban) within the past 48 hours
-
Received glycoprotein IIb/IIIa inhibitors within the past 14 days
-
Pre-existing neurological or psychiatric disease which confounded the neurological or functional evaluations e.g., baseline modified Rankin score >3
-
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
-
Current participation in another research drug treatment or interventional device trial - Subjects could not start another experimental agent until after 90 days
-
Informed consent from the patient or the legally authorized representative was not or could not be obtained
-
High density lesion consistent with hemorrhage of any degree
-
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Argatroban Argatroban 100µg/kg bolus followed by 3µg/kg per minute for 12 hours Eptifibatide Eptifibatide 135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours
- Primary Outcome Measures
Name Time Method 90-day Utility Weighted Modified Rankin Scores (UW-mRS) 90 days after randomization The modified Rankin scale is a 7 point ordinal scale ranging from 0="no symptoms" to 6="death" . For the primary analysis, the scale was analyzed with patient-centered utility weights. We assigned the following utility weights to the seven levels: 10, 9.1,, 7.6, 6.5, 3.3, 0, 0 (with higher scores indicating a better outcome).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With NIHSS Less Than or Equal to 2 at 24 Hours 24 hours after randomization National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit. This is a dichotomous analysis with a cutpoint of 0,1,2 defining the event.
Change From Baseline to 24-hour NIHSS 24 hours after randomization National Institute of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating worse neurologic deficit.
Percentage of Participants With 90-day mRS 0 or 1 (or Return to Their Historical mRS) 90 days after randomization The modified Rankin scale (mRS) is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes. For patients with a pre-stroke mRS of greater than 0 or 1, these patients had to return to their historical (pre-stroke) value to be counted as a success.
Percentage of Participants With 90-day mRS 0, 1 or 2 (or Return to Their Historical mRS) 90 days after randomization modified Rankin scale is a 7 point scale ranging from 0="no symptoms" to 6="death" where lower scores are better outcomes.
90-day mRS 90 days after randomization modified Rankin scale is a 7 point ordinal scale ranging from 0="no symptoms at all" to 6="death" where lower scores are better outcomes.
90-day EQ-5D 90 days after randomization EuroQol Five-Dimension (EQ-5D) is a measure of health-related quality of life ranging from -0.59 to 1 where 1 is the best possible health state.
Pre-thrombectomy Modified TICI Score of 2B. baseline The modified thrombolysis in cerebral infarction (TICI) score prior to endovascular thrombectomy procedure. The modified pre-thrombectomy TICI score is a 4 point scale with possible values of 0, 1, 2A, and 2B. The values are defined as follows: 0=No flow, 1=Penetration without distal branch filling, 2A=\<50% partial reperfusion, and 2B=50%-99% partial reperfusion.
Post-thrombectomy Modified TICI Score of 2B or 3 baseline The modified thrombolysis in cerebral infarction (TICI) score prior to endovascular thrombectomy procedure. The modified post-thrombectomy TICI score is a 5 point scale with possible values of 0, 1, 2A, 2B, 3. The values are defined as follows: 0=No flow, 1=Penetration without distal branch filling, 2A=\<50% partial reperfusion, 2B=50%-99% partial reperfusion, and 3=Completed reperfusion
Trial Locations
- Locations (61)
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Jackson Memorial Hospital
🇺🇸Miami, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Memorial Hermann-Texas Medical Center
🇺🇸Houston, Texas, United States
UCSD Medical Center - Hillcrest Hospital
🇺🇸San Diego, California, United States
Mercy Health West Hospital
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
The Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
Mayo Clinic Hospital
🇺🇸Jacksonville, Florida, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States
Cleveland Clinic Akron General
🇺🇸Akron, Ohio, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
UVA Medical Center
🇺🇸Charlottesville, Virginia, United States
St. Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Vanderbilt University Hospital
🇺🇸Nashville, Tennessee, United States
University of Utah Healthcare
🇺🇸Salt Lake City, Utah, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
University of Alabama Hospital
🇺🇸Birmingham, Alabama, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
St. Jude Medical Center
🇺🇸Fullerton, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Central DuPage Hospital
🇺🇸Winfield, Illinois, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Trinity Health Saint Mary's
🇺🇸Grand Rapids, Michigan, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
McLaren Flint
🇺🇸Flint, Michigan, United States
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
SUNY Upstate University Hospital
🇺🇸Syracuse, New York, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Mercy Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
St. John Medical Center
🇺🇸Tulsa, Oklahoma, United States
UCSD Health La Jolla
🇺🇸La Jolla, California, United States
Baptist Medical Center Jacksonville
🇺🇸Jacksonville, Florida, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
Javon Bea Hospital - Riverside
🇺🇸Rockford, Illinois, United States
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
South Texas Health System McAllen
🇺🇸McAllen, Texas, United States
University of Minnesota Medical Center Hospital
🇺🇸Minneapolis, Minnesota, United States
University of Michigan University Hospital
🇺🇸Ann Arbor, Michigan, United States
Forsyth Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Saint Luke's Hospital
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States