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

Acute Stroke Clinical Trial

— MR WITNESS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01282242
• Other study ID #: MR WITNESS
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 19, 2011
• Last updated: March 21, 2016
• Start date: January 2011
• Est. completion date: December 2016

Study information

• Verified date: March 2016
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Stroke

Intervention

Drug:
• IV rt-PA
open-label

Locations

Country	Name	City	State
United States	Seton/UT Southwestern Medical Center	Austin	Texas
United States	NIH/ NINDS, Washington Hospital, Suburban Hospital	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Iowa	Iowa City	Iowa
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Intermountain Healthcare	Murray	Utah
United States	Washington University School of Medicine/Barnes Jewish Hospital	St. Louis	Missouri
United States	University of Arizona	Tucson	Arizona
United States	University of Massachusetts	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Lee Schwamm	Genentech, Inc., 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	rt-PA Safety	rt-PA safety as evidenced by no significant increase in symptomatic ICH rates	within 24 hours of last know well and MRI evidence of early stroke	Yes