Acute StrokePhase 2MR WITNESSNCT01282242

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

A Phase 2 study testing IV rt-PA in people with Acute Stroke, run by Lee Schwamm at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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… Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Acute Stroke
What is being tested?: IV rt-PA
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 88 participants
Where: 14 sitesUnited States
Study dates: Jan 2011to May 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 20Show fewer

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.

Trial locations and contacts

14 sites in 1 country.

City, postcode or hospital

14 sites in 1 country

United States14 sites

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

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Acute Stroke
Being tested: IV rt-PA
Keywords: acute stroke, IV rt-PA, Activase, Alteplase
Medical subject headings: Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IV rt-PADrug
Also called Alteplase, Activase
open-label

Study groups in NCT01282242
Study group	Role	What they receive
IV rt-PA	Experimental	open-label Receives: Drug: IV rt-PA

What is being measured

The primary outcome is the main question the study is designed to answer.

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 .
Measured: Within 7 days from tPA administration.

Secondary outcomes (1)

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.
Measured: Within 96 hours of tPA administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011May 2016

First posted24 Jan 2011 (estimated)
Study startJan 2011
Primary completionJan 2016
Study completionMay 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Acute StrokeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 88 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01282242
Sponsor's protocol ID: 2010P001880
Acronym: MR WITNESS
Status last verified: May 2017
First submitted: 19 Jan 2011
Last updated: 15 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 29689135
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.
PubMed 27834750

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: MR WITNESS: A Phase IIa Safety Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients
ClinicalTrials.gov ID: NCT01282242
Acronym / sponsor ID: MR WITNESS / 2010P001880
Conditions: Acute Stroke
Keywords: acute stroke, IV rt-PA, Activase, Alteplase
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 88 participants (actual)
Lead sponsor: Lee SchwammUniversity, hospital or other
Collaborators: National Institute of Neurological Disorders and Stroke (NINDS), Genentech, Inc.
Study start: Jan 2011
Primary completion: Jan 2016 (actual)
Study completion: May 2016 (actual)
First posted: 24 Jan 2011 (estimated)
Results: Posted 11 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
IV rt-PA	Experimental	Drug: IV rt-PAopen-label

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (20 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IV rt-PAAlso: Alteplase, Activaseopen-label	Drug	IV rt-PA

Primary outcome

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 .

1 secondary outcome

Number of Subjects With Symptomatic Cerebral Edema
Time frame: Within 96 hours of tPA administration

Results and safety

Results posted to the registry on 11 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Primary SIR <1.15	80	80
Secondary SIR <1.25	8	8

Primary outcome: Number of Subjects With Symptomatic Intracerebral Hemorrhage

Time frame: Within 7 days from tPA administration.. Count of participants. Unit: Participants

Measure	SIR <1.15 n = 80	SIR < 1.25 n = 8
Value	1	1

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SIR <1.15	22 of 80 (27.5%)	56 of 80 (70%)	7 of 80
SIR <1.25	5 of 8 (62.5%)	8 of 8 (100%)	1 of 8

Limitations and caveats (from the sponsor): This was a single arm open label trial. Genetech provided alteplase free of charge for this NINDS sponsored study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29689135Schwamm 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.
Derived from this study: PubMed 27834750Ali 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lee Schwamm, MD principal investigator

Massachusetts General Hospital

Steven Warach, MD, PhD principal investigator

NINDS/Seton/UT Southwestern Clinical Research Institute of Austin

Ona Wu, PhD principal investigator

Massachusetts General Hospital

14 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IV rt-PA in people with Acute Stroke, run by Lee Schwamm at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Symptomatic Intracerebral Hemorrhage (time frame: Within 7 days from tPA administration.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01282242, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2017.