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

May 24, 2017 updated by: Lee Schwamm

MR WITNESS: A Phase IIa Safety Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • NIH/ NINDS, Washington Hospital, Suburban Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine/Barnes Jewish Hospital
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • University of Tennessee Health Science Center
    • Texas
      • Austin, Texas, United States, 78701
        • Seton/UT Southwestern Medical Center
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Healthcare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IV rt-PA
open-label
Drug: IV rt-PA
open-label
Other Names:
  • Alteplase, Activase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Symptomatic Intracerebral Hemorrhage
Time Frame: Within 7 days from tPA administration.
Safety of IV rt-PA as evident by rates of symptomatic ICH defined by an increase of 4 points or more on the NIHSS .
Within 7 days from tPA administration.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Symptomatic Cerebral Edema
Time Frame: Within 96 hours of tPA administration
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.
Within 96 hours of tPA administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lee Schwamm

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.

Investigators

  • Principal Investigator: Lee Schwamm, MD, Massachusetts General Hospital
  • Principal Investigator: Steven Warach, MD, PhD, NINDS/Seton/UT Southwestern Clinical Research Institute of Austin
  • Principal Investigator: Ona Wu, PhD, Massachusetts General Hospital
  • Principal Investigator: Lawrence Latour, PhD, NIH Intramural Stroke Program/Suburban Hospital/Washington Hospital Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

January 19, 2011

First Submitted That Met QC Criteria

January 21, 2011

First Posted (Estimate)

January 24, 2011

Study Record Updates

Last Update Posted (Actual)

June 15, 2017

Last Update Submitted That Met QC Criteria

May 24, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010P001880

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Stroke

Clinical Trials on IV rt-PA

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe