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A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients (MR WITNESS)

Primary Purpose

Acute Stroke

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IV rt-PA
Sponsored by
Lee Schwamm
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Stroke focused on measuring acute stroke, IV rt-PA, Activase, Alteplase

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age, 18 to 85 years inclusive
  • Brain MRI findings consistent with early stroke onset
  • Clinical diagnosis of acute ischemic stroke with disabling neurological deficit
  • Stroke symptoms present for at least 30 minutes with no significant improvement before treatment
  • Be last known well (without stroke symptoms) within 24 hours of triage
  • Be able to receive IV rt-PA within 4.5 hours from the time the symptoms were discovered.
  • MRI diagnostic of acute ischemic stroke and consistent with clinical syndrome
  • Time between completion of qualifying MRI studies to treatment initiation ≤ 1 hour

Exclusion Criteria:

  • History of intracranial hemorrhage
  • Symptoms rapidly improving or only minor before start of study drug.
  • Severe stroke as assessed clinically (e.g., NIHSS score >25) or by appropriate imaging techniques (lesion volume > one-third of MCA by visual inspection or >100 cm3 using the ellipsoid estimation formula of ABC/2)
  • Stroke or serious head trauma within the previous 3 months
  • Administration of heparin within the 48 hours preceding the onset of stroke, with an activated partial-thromboplastin time at presentation exceeding the upper limit of the normal range
  • Platelet count of less than 100,000 per cubic millimeter
  • Uncontrolled hypertension defined as systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg that cannot be controlled except with continuous parenteral antihypertensive medication
  • Blood glucose less than 50 mg per deciliter or greater than 400 mg per deciliter
  • Symptoms suggestive of subarachnoid hemorrhage, even if CT/MRI scan was normal
  • Oral anticoagulant treatment, regardless of INR.
  • Major surgery or severe trauma within the previous 3 months
  • Other major disorders associated with an increased risk of bleeding
  • Eligible for rt-PA therapy per institutional protocol as part of routine clinical practice
  • Non-ischemic etiology demonstrated by neuroimaging
  • Neuroimaging (CT or gradient echo MRI) evidence of acute or chronic ICH (non-microbleed)
  • Presence of 10 or more microbleeds on GRE (suggestive of amyloid angiopathy)
  • Any contraindication for MRI, e.g. presence of a pacemaker, ferromagnetic aneurysm clip, etc, pre-menopausal women with a positive pregnancy blood test, or severe claustrophobia.
  • Poor quality MRI- images are not interpretable
  • In the opinion of the investigator, the patient is not an appropriate candidate for IV rt-PA
  • Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.

Sites / Locations

  • University of Arizona
  • Cedars Sinai Medical Center
  • Ronald Reagan UCLA Medical Center
  • Rush University Medical Center
  • University of Iowa
  • NIH/ NINDS, Washington Hospital, Suburban Hospital
  • Massachusetts General Hospital
  • Boston Medical Center
  • Beth Israel Deaconess Medical Center
  • University of Massachusetts
  • Washington University School of Medicine/Barnes Jewish Hospital
  • University of Tennessee Health Science Center
  • Seton/UT Southwestern Medical Center
  • Intermountain Healthcare

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IV rt-PA

Arm Description

open-label

Outcomes

Primary Outcome Measures

Number of Subjects With Symptomatic Intracerebral Hemorrhage
Safety of IV rt-PA as evident by rates of symptomatic ICH defined by an increase of 4 points or more on the NIHSS .

Secondary Outcome Measures

Number of Subjects With Symptomatic Cerebral Edema
Safety of IV rt-PA as evident by rates of symptomatic cerebral edema defined as brain edema with mass effect as the predominant cause of clinical deterioration.

Full Information

First Posted
January 19, 2011
Last Updated
May 24, 2017
Sponsor
Lee Schwamm
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01282242
Brief Title
A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients
Acronym
MR WITNESS
Official Title
MR WITNESS: A Phase IIa Safety Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lee Schwamm
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study was jointly developed and is jointly led by investigators at Massachusetts General Hospital and the intramural division of NINDS. We are doing this research study to find out if Activase ® (also called alteplase or rt-PA) can safely be given to people with an acute ischemic stroke when their stroke onset was not witnessed making them ineligible for standard thrombolytic (clot busting) therapy. We also want to find out if rt-PA can help people recover better from their stroke. The purpose of this study is to: 1) see if it is safe to give intravenous (IV) rt-PA to people with unwitnessed stroke but with MRI evidence of early ischemic stroke, 2) see if rt-PA is effective if given to people who are selected for treatment based on MRI evidence of an early stroke, and 3) get information about this new MRI diagnostic methods for guiding stroke treatment.
Detailed Description
This study was jointly developed and is jointly led by Massachusetts General Hospital and the NINDS. This is a multi-center, open-label, Phase IIa safety study in adult acute ischemic stroke patients to determine if it is safe to extend intravenous thrombolytic treatment to subjects who are evaluated within 24 hours from last known well ("stroke onset") and eligible to receive thrombolytic treatment within 4.5 hours from symptom discovery with the assistance of an MRI-based "witness" when no human witness of stroke onset is available. The study is designed to investigate the safety in using standard diagnostic MRI in selecting patients for thrombolytic therapy when the last known well time places the patient beyond the current IV thrombolytic time-window.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Stroke
Keywords
acute stroke, IV rt-PA, Activase, Alteplase

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV rt-PA
Arm Type
Experimental
Arm Description
open-label
Intervention Type
Drug
Intervention Name(s)
IV rt-PA
Other Intervention Name(s)
Alteplase, Activase
Intervention Description
open-label
Primary Outcome Measure Information:
Title
Number of Subjects With Symptomatic Intracerebral Hemorrhage
Description
Safety of IV rt-PA as evident by rates of symptomatic ICH defined by an increase of 4 points or more on the NIHSS .
Time Frame
Within 7 days from tPA administration.
Secondary Outcome Measure Information:
Title
Number of Subjects With Symptomatic Cerebral Edema
Description
Safety of IV rt-PA as evident by rates of symptomatic cerebral edema defined as brain edema with mass effect as the predominant cause of clinical deterioration.
Time Frame
Within 96 hours of tPA administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age, 18 to 85 years inclusive Brain MRI findings consistent with early stroke onset Clinical diagnosis of acute ischemic stroke with disabling neurological deficit Stroke symptoms present for at least 30 minutes with no significant improvement before treatment Be last known well (without stroke symptoms) within 24 hours of triage Be able to receive IV rt-PA within 4.5 hours from the time the symptoms were discovered. MRI diagnostic of acute ischemic stroke and consistent with clinical syndrome Time between completion of qualifying MRI studies to treatment initiation ≤ 1 hour Exclusion Criteria: History of intracranial hemorrhage Symptoms rapidly improving or only minor before start of study drug. Severe stroke as assessed clinically (e.g., NIHSS score >25) or by appropriate imaging techniques (lesion volume > one-third of MCA by visual inspection or >100 cm3 using the ellipsoid estimation formula of ABC/2) Stroke or serious head trauma within the previous 3 months Administration of heparin within the 48 hours preceding the onset of stroke, with an activated partial-thromboplastin time at presentation exceeding the upper limit of the normal range Platelet count of less than 100,000 per cubic millimeter Uncontrolled hypertension defined as systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg that cannot be controlled except with continuous parenteral antihypertensive medication Blood glucose less than 50 mg per deciliter or greater than 400 mg per deciliter Symptoms suggestive of subarachnoid hemorrhage, even if CT/MRI scan was normal Oral anticoagulant treatment, regardless of INR. Major surgery or severe trauma within the previous 3 months Other major disorders associated with an increased risk of bleeding Eligible for rt-PA therapy per institutional protocol as part of routine clinical practice Non-ischemic etiology demonstrated by neuroimaging Neuroimaging (CT or gradient echo MRI) evidence of acute or chronic ICH (non-microbleed) Presence of 10 or more microbleeds on GRE (suggestive of amyloid angiopathy) Any contraindication for MRI, e.g. presence of a pacemaker, ferromagnetic aneurysm clip, etc, pre-menopausal women with a positive pregnancy blood test, or severe claustrophobia. Poor quality MRI- images are not interpretable In the opinion of the investigator, the patient is not an appropriate candidate for IV rt-PA Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee Schwamm, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steven Warach, MD, PhD
Organizational Affiliation
NINDS/Seton/UT Southwestern Clinical Research Institute of Austin
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ona Wu, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lawrence Latour, PhD
Organizational Affiliation
NIH Intramural Stroke Program/Suburban Hospital/Washington Hospital Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Cedars Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
NIH/ NINDS, Washington Hospital, Suburban Hospital
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Massachusetts
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Washington University School of Medicine/Barnes Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Tennessee Health Science Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Seton/UT Southwestern Medical Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78701
Country
United States
Facility Name
Intermountain Healthcare
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29689135
Citation
Schwamm LH, Wu O, Song SS, Latour LL, Ford AL, Hsia AW, Muzikansky A, Betensky RA, Yoo AJ, Lev MH, Boulouis G, Lauer A, Cougo P, Copen WA, Harris GJ, Warach S; MR WITNESS Investigators. Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results. Ann Neurol. 2018 May;83(5):980-993. doi: 10.1002/ana.25235. Epub 2018 Apr 27.
Results Reference
derived
PubMed Identifier
27834750
Citation
Ali SF, Siddiqui K, Ay H, Silverman S, Singhal A, Viswanathan A, Rost N, Lev M, Schwamm LH. Baseline Predictors of Poor Outcome in Patients Too Good to Treat With Intravenous Thrombolysis. Stroke. 2016 Dec;47(12):2986-2992. doi: 10.1161/STROKEAHA.116.014871. Epub 2016 Nov 10.
Results Reference
derived

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A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients

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