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

NCT01282242 | Completed Phase 2 Results DMC

• 1 other identifier: 2010P001880
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 14

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.

Conditions

Acute Stroke

Keywords

acute stroke, IV rt-PA, Activase, Alteplase

Outcome Measures

Primary Outcomes (1)

• 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 .

  Within 7 days from tPA administration.

Secondary Outcomes (1)

• Number of Subjects With Symptomatic Cerebral Edema

  Within 96 hours of tPA administration

Study Arms (1)

IV rt-PA

EXPERIMENTAL

open-label

Drug: IV rt-PA

Interventions

IV rt-PA DRUG

open-label

Also known as: Alteplase, Activase

IV rt-PA

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Lee Schwamm: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Genentech, Inc.: collaborator

Study Sites (14)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

NIH/ NINDS, Washington Hospital, Suburban Hospital

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

Washington University School of Medicine/Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38105, United States

Location

Seton/UT Southwestern Medical Center

Austin, Texas, 78701, United States

Location

Intermountain Healthcare

Murray, Utah, 84107, United States

Location

Related Publications (2)

• 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.

  PMID: 29689135 DERIVED

• 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.

  PMID: 27834750 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Limitations and Caveats

This was a single arm open label trial. Genetech provided alteplase free of charge for this NINDS sponsored study.

Results Point of Contact

• Title: Lee H. Schwamm, MD
• Organization: Massachusetts General Hospital

lschwamm@mgh.harvard.edu

617-724-1597

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Chairman, Department of Neurology

Study Record Dates

• First Submitted: January 19, 2011
• First Posted: January 24, 2011
• Study Start: January 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 15, 2017
• Results First Posted: April 11, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)