ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01282242
Recruitment Status : Completed
First Posted : January 24, 2011
Results First Posted : April 11, 2017
Last Update Posted : June 15, 2017
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Information provided by (Responsible Party):
Lee Schwamm, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Stroke
Intervention Drug: IV rt-PA
Enrollment 88

Recruitment Details Subjects were recruited between January 2011 and February 2016 from 14 sites across the continental United States, and enrolled in 10 of those sites.
Pre-assignment Details Subjects diagnosed with acute ischemic stroke, last known well within 24 hours of triage and able to receive IV rt-PA within 4.5 hours from symptom discovery based on MRI findings consistent with early stroke onset, were eligible. MRI Signal Intensity Ration values were defined as <1.15 for the primary and <1.25 for the secondary arm of the trial.
Arm/Group Title Primary SIR <1.15 Secondary SIR <1.25
Hide Arm/Group Description MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI) MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Period Title: Overall Study
Started 80 8
Completed 80 8
Not Completed 0 0
Arm/Group Title SIR <1.15 SIR <1.25 Total
Hide Arm/Group Description MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI) MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI) Total of all reporting groups
Overall Number of Baseline Participants 80 8 88
Hide Baseline Analysis Population Description
Analysis population consists of all subjects enrolled who suffered an unwitnessed stroke and qualified per AHA guidelines to receive IV tPA within a window of 3-4.5 hours since symptom discovery and whose signal intensity ratio (SIR) on MRI was <1.15 for primary arm and <1.25 for secondary arm.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 80 participants 8 participants 88 participants
67.46  (13.5) 67.13  (11.63) 67.43  (13.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 8 participants 88 participants
Female
37
  46.3%
4
  50.0%
41
  46.6%
Male
43
  53.8%
4
  50.0%
47
  53.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 8 participants 88 participants
Hispanic or Latino
6
   7.5%
0
   0.0%
6
   6.8%
Not Hispanic or Latino
73
  91.3%
8
 100.0%
81
  92.0%
Unknown or Not Reported
1
   1.3%
0
   0.0%
1
   1.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 8 participants 88 participants
American Indian or Alaska Native
1
   1.3%
0
   0.0%
1
   1.1%
Asian
2
   2.5%
1
  12.5%
3
   3.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
28
  35.0%
5
  62.5%
33
  37.5%
White
47
  58.8%
2
  25.0%
49
  55.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   2.5%
0
   0.0%
2
   2.3%
NIH Stroke Scale (NIHSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 80 participants 8 participants 88 participants
9.31  (5.87) 10.13  (4.64) 9.35  (5.91)
[1]
Measure Description: NIH Stroke Scale measured the severity of the stroke. The scores ranged between 4 to 42, with higher score indicating worsening of the Outcome. NIHSS score above 20 is indicative of severe stroke.
Modified Rankin Scale   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 80 participants 8 participants 88 participants
0.48  (1.09) 1.38  (2.26) 1.18  (1.72)
[1]
Measure Description: Modified Rankin Scale (mRS) measures a subjects degree of disability on a scale of 0 to 6, where 0 is no disability and 6 is death.
1.Primary Outcome
Title Number of Subjects With Symptomatic Intracerebral Hemorrhage
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title SIR <1.15 SIR < 1.25
Hide Arm/Group Description:
MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Overall Number of Participants Analyzed 80 8
Measure Type: Count of Participants
Unit of Measure: Participants
1 1
2.Secondary Outcome
Title Number of Subjects With Symptomatic Cerebral Edema
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title SIR <1.15 SIR < 1.25
Hide Arm/Group Description:
MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Overall Number of Participants Analyzed 80 8
Measure Type: Count of Participants
Unit of Measure: Participants
3 0
Time Frame Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SIR <1.15 SIR <1.25
Hide Arm/Group Description MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI) MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) <1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
All-Cause Mortality
SIR <1.15 SIR <1.25
Affected / at Risk (%) Affected / at Risk (%)
Total   7/80 (8.75%)   1/8 (12.50%) 
Show Serious Adverse Events Hide Serious Adverse Events
SIR <1.15 SIR <1.25
Affected / at Risk (%) Affected / at Risk (%)
Total   22/80 (27.50%)   5/8 (62.50%) 
Cardiac disorders     
Atrial Fibrillation * 1  3/80 (3.75%)  0/8 (0.00%) 
Cardio-Respiratory Arrest * 1  1/80 (1.25%)  0/8 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal Heamorrhage * 1  1/80 (1.25%)  0/8 (0.00%) 
Upper Gastrointestinal Haemorrhage * 1  1/80 (1.25%)  0/8 (0.00%) 
General disorders     
Asthenia * 1  1/80 (1.25%)  0/8 (0.00%) 
Death * 1  3/80 (3.75%)  0/8 (0.00%) 
Infections and infestations     
Pneumonia * 1  1/80 (1.25%)  0/8 (0.00%) 
Septic Shock * 1  1/80 (1.25%)  0/8 (0.00%) 
Injury, poisoning and procedural complications     
FALL * 1  0/80 (0.00%)  1/8 (12.50%) 
Metabolism and nutrition disorders     
Hyperkalaemia * 1  1/80 (1.25%)  0/8 (0.00%) 
Nervous system disorders     
Brain Oedema * 1  6/80 (7.50%)  0/8 (0.00%) 
Cerebral Heamorrhage * 1  2/80 (2.50%)  1/8 (12.50%) 
Cerebrovascular Accident * 1  3/80 (3.75%)  1/8 (12.50%) 
Convulsion * 1  2/80 (2.50%)  0/8 (0.00%) 
Haemorrhage Intracranial * 1  2/80 (2.50%)  0/8 (0.00%) 
Ischaemic Stroke * 1  1/80 (1.25%)  0/8 (0.00%) 
Neurological Symptom * 1  1/80 (1.25%)  0/8 (0.00%) 
BRAIN HERNIATION * 1  0/80 (0.00%)  1/8 (12.50%) 
Psychiatric disorders     
Confusional State * 1  2/80 (2.50%)  0/8 (0.00%) 
Mental Status Changes * 1  2/80 (2.50%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia Aspiration * 1  1/80 (1.25%)  0/8 (0.00%) 
Respiratory Distress * 1  1/80 (1.25%)  0/8 (0.00%) 
Respiratory Failure * 1  4/80 (5.00%)  0/8 (0.00%) 
Vascular disorders     
Heamatoma * 1  1/80 (1.25%)  0/8 (0.00%) 
ANGIOEDEMA * 1  0/80 (0.00%)  1/8 (12.50%) 
CAROTID ARTERY STENOSIS * 1  0/80 (0.00%)  1/8 (12.50%) 
MYOCARDIAL INFARCTION * 1  0/80 (0.00%)  1/8 (12.50%) 
1
Term from vocabulary, MedDRA (16.1)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SIR <1.15 SIR <1.25
Affected / at Risk (%) Affected / at Risk (%)
Total   56/80 (70.00%)   8/8 (100.00%) 
Gastrointestinal disorders     
Constipation * 1  7/80 (8.75%)  1/8 (12.50%) 
Nausea * 1  8/80 (10.00%)  1/8 (12.50%) 
Vomiting * 1  6/80 (7.50%)  0/8 (0.00%) 
General disorders     
Pyrexia * 1  8/80 (10.00%)  0/8 (0.00%) 
GINGIVAL BLEEDING * 1  0/80 (0.00%)  1/8 (12.50%) 
Infections and infestations     
Urinary Tract Infection * 1  12/80 (15.00%)  0/8 (0.00%) 
Injury, poisoning and procedural complications     
HEAD INJURY * 1  0/80 (0.00%)  1/8 (12.50%) 
LIMB INJURY * 1  0/80 (0.00%)  1/8 (12.50%) 
Metabolism and nutrition disorders     
HYPOGLYCAEMIA * 1  0/80 (0.00%)  1/8 (12.50%) 
Musculoskeletal and connective tissue disorders     
MUSCLE SPASMS * 1  1/80 (1.25%)  1/8 (12.50%) 
OROPHARYNGEAL PAIN * 1  0/80 (0.00%)  1/8 (12.50%) 
Nervous system disorders     
Cerebral Haemorrhage * 1  4/80 (5.00%)  0/8 (0.00%) 
Heamorrhagic Transformation * 1  18/80 (22.50%)  1/8 (12.50%) 
Headache * 1  13/80 (16.25%)  0/8 (0.00%) 
Amnesia * 1  0/80 (0.00%)  1/8 (12.50%) 
Psychiatric disorders     
Agitation * 1  4/80 (5.00%)  0/8 (0.00%) 
Depression * 1  4/80 (5.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
ATELECTASIS * 1  0/80 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders     
Ecchymosis * 1  5/80 (6.25%)  0/8 (0.00%) 
Petechiae * 1  4/80 (5.00%)  2/8 (25.00%) 
INJECTION SITE EXTRAVASATION * 1  1/80 (1.25%)  1/8 (12.50%) 
Vascular disorders     
ATRIAL FIBRILLATION * 1  0/80 (0.00%)  1/8 (12.50%) 
1
Term from vocabulary, MedDRA (16.1)
*
Indicates events were collected by non-systematic assessment
This was a single arm open label trial. Genetech provided alteplase free of charge for this NINDS sponsored study.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Lee H. Schwamm, MD
Organization: Massachusetts General Hospital
Phone: 617-724-1597
Responsible Party: Lee Schwamm, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01282242     History of Changes
Other Study ID Numbers: 2010P001880
First Submitted: January 19, 2011
First Posted: January 24, 2011
Results First Submitted: February 27, 2017
Results First Posted: April 11, 2017
Last Update Posted: June 15, 2017