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Safety of Intravenous Thrombolysis for Wake-up Stroke (Wake-Up Stroke)

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ClinicalTrials.gov Identifier: NCT01183533
Recruitment Status : Completed
First Posted : August 17, 2010
Results First Posted : November 25, 2014
Last Update Posted : November 25, 2014
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Sean Savitz, The University of Texas Health Science Center, Houston

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ischemic Stroke
Intervention Drug: Alteplase (iv t-PA)
Enrollment 40
Recruitment Details Study was open for enrollment (began recruiting and screening for eligible patients) on July 13, 2010. The date of first enrollment was October 5, 2010 and the date of last enrollment was October 5, 2013. All patients were enrolled at one of five participating centers.
Pre-assignment Details  
Arm/Group Title Off Label Rt-PA
Hide Arm/Group Description

Off label rt-PA used on all subjects enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Alteplase (iv t-PA): 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

Period Title: Overall Study
Started 40 [1]
Completed 40 [2]
Not Completed 0
[1]
Between Oct 2010 and Oct 2013.
[2]
- all pre-planned 40 patients received the study medication.
Arm/Group Title Off Label Rt-PA
Hide Arm/Group Description

Off label rt-PA used on all subjects enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Alteplase (iv t-PA): 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
60.8  (13.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
20
  50.0%
Male
20
  50.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 40 participants
Caucasian, Non-Hispanic 17
Caucasian, Hispanic 6
African American 16
Asian 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 participants
40
National Institutes of Health Stroke Scale score, median (range)   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 40 participants
6.5
(2 to 24)
[1]
Measure Description: National Institutes of Health Stroke Scale (NIHSS) score is a numerical 0-42 point scale that defines the severity of stroke deficits. It is routinely used in both the clinical assessment of patients as well as a research tool. Zero indicates a normal exam with no stroke deficits; whereas 42 indicates a severely affected individual who is comatose and unable to move their extremities. Unit of measure: "units on a scale".
1.Primary Outcome
Title Frequency of Symptomatic Hemorrhagic Transformation Safety of iv Rt-PA in Wake up Stroke Patients
Hide Description The primary outcome of this study is the frequency of symptomatic hemorrhagic transformation evident within 24 hours of treatment with IV t-PA. Symptomatic was defined as significant clinical deterioration with at least a 4 point or more increase in the NIH Stroke scale.
Time Frame 24 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Off Label Rt-PA
Hide Arm/Group Description:

Off label rt-PA used on all subjects enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Alteplase (iv t-PA): 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: cases.
0
2.Secondary Outcome
Title 90-day Modified Rankin Scale (mRS) Score 0 or 1
Hide Description Number of patients with mRS of 0 or 1 at 90 days. The mRS is a clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It has a minimum of 0 and a maximum of 6. Zero represents a patient that has no disability or residual stroke symptoms. A score of 1 is defined as: no significant disability: despite symptoms, able to carry out all usual duties and activities. The maximum score, 6, indicates death. A score of 2 is defined as slight disability: unable to perform all previous activities but able to look after own affairs without assistance; a score of 3 is defined as moderate disability: requiring some help but able to walk without assistance; a score of 4 is moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs without assistance; a score of 5 is severe disability: bedridden, incontinent and requiring constant nursing care and attention.
Time Frame 90 days
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Hide Analysis Population Description
^ Note: 2 patients were not available for 90-day follow-up assessments.
Arm/Group Title Off Label Rt-PA
Hide Arm/Group Description:

Off label rt-PA used on all subjects enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Alteplase (iv t-PA): 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

Overall Number of Participants Analyzed 38
Measure Type: Number
Unit of Measure: participants
20
3.Secondary Outcome
Title Mortality
Hide Description [Not Specified]
Time Frame 90 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Note: although 2 patients were not available for complete day 90 assessments, family/patient communication provided necessary mortality information.
Arm/Group Title Off Label Rt-PA
Hide Arm/Group Description:

Off label rt-PA used on all subjects enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Alteplase (iv t-PA): 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: participants
2
Time Frame 30 days from rt-PA treatment.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Off Label Rt-PA
Hide Arm/Group Description

Off label rt-PA used on all subjects enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Alteplase (iv t-PA): 0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

All-Cause Mortality
Off Label Rt-PA
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Off Label Rt-PA
Affected / at Risk (%) # Events
Total   6/40 (15.00%)    
General disorders   
Death  [1]  1/40 (2.50%)  1
Infections and infestations   
Abscess  [2]  1/40 (2.50%)  1
Nervous system disorders   
New (recurrent) Ischemic Stroke  [3]  2/40 (5.00%)  2
Cerebral Edema, malignant  [4]  1/40 (2.50%)  1
Seizures with neurological deterioration   1/40 (2.50%)  1
Respiratory, thoracic and mediastinal disorders   
Death  [5]  1/40 (2.50%)  1
Respiratory Failure  [6]  1/40 (2.50%)  1
Indicates events were collected by systematic assessment
[1]
Death from sepsis and aspiration pneumonia.
[2]
Abscess at Feeding tube site, requiring surgical bedside drainage and antibiotics.
[3]
New, interval ischemic stroke.
[4]
Malignant cerebral edema requiring decompressive hemicraniectomy.
[5]
Respiratory Failure leading to Death Etiology: withdrawal of support after patient suffered from pneumonia, sepsis and respiratory failure.
[6]
leading to mechanical ventilation and traceostomy.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Off Label Rt-PA
Affected / at Risk (%) # Events
Total   30/40 (75.00%)    
Blood and lymphatic system disorders   
Hemorrhage (bleeding from ear)   1/40 (2.50%)  1
Anemia   9/40 (22.50%)  9
Increased INR (international normalized ratio)   4/40 (10.00%)  4
Neutrophilia   1/40 (2.50%)  1
Lymphopenia   1/40 (2.50%)  1
Monocytopenia   1/40 (2.50%)  1
Monocytosis   1/40 (2.50%)  1
Increased PTT (partial thromboplastin time)   1/40 (2.50%)  1
Cardiac disorders   
Atrial Fibrillation   4/40 (10.00%)  4
Gastrointestinal disorders   
Nausea   1/40 (2.50%)  1
Pneumoperitoneum   1/40 (2.50%)  1
General disorders   
Hypocalcemia   7/40 (17.50%)  7
Vertigo with nausea   1/40 (2.50%)  1
Insomnia   1/40 (2.50%)  1
Increased ESR rate (erythrocyte segmentation)   1/40 (2.50%)  1
Sore Throat   1/40 (2.50%)  1
Hypoglycemia   1/40 (2.50%)  1
Hyperglycemia   13/40 (32.50%)  16
Hypokalemia   3/40 (7.50%)  3
Hyperkalemia   3/40 (7.50%)  3
Hypernatremia   3/40 (7.50%)  3
Hypomagnesemia   1/40 (2.50%)  1
Hyponatremia   1/40 (2.50%)  1
Hypermagnesemia   1/40 (2.50%)  1
Hypophosphatemia   1/40 (2.50%)  1
Infections and infestations   
Fever   3/40 (7.50%)  3
Cellulitis   1/40 (2.50%)  1
Musculoskeletal and connective tissue disorders   
Musculoskeletal Pain   3/40 (7.50%)  3
Nervous system disorders   
Asymptomatic Intracranial Hemorrhage   6/40 (15.00%)  6
Encephalopathy   2/40 (5.00%)  2
Neurological Worsening   1/40 (2.50%)  1
Renal and urinary disorders   
Urinary Tract Infection   3/40 (7.50%)  3
Elevated Creatinine and/or BUN   3/40 (7.50%)  5
Hematuria   1/40 (2.50%)  1
Acute Kidney Injury   1/40 (2.50%)  1
Respiratory, thoracic and mediastinal disorders   
Shortness of breath (dyspnea)   3/40 (7.50%)  3
Lung infiltrates (lower lobe)   1/40 (2.50%)  1
Pleural Effusion   1/40 (2.50%)  1
COPD (chronic obstructive pulmonary disease) Exacerbation   1/40 (2.50%)  1
Skin and subcutaneous tissue disorders   
Orolingual Angioedema   2/40 (5.00%)  2
Vascular disorders   
Hypotension   1/40 (2.50%)  1
Hypertension (uncontrolled)   1/40 (2.50%)  1
Deep Venous Thrombosis   2/40 (5.00%)  2
Limb Ischemia  [1]  1/40 (2.50%)  1
Indicates events were collected by systematic assessment
[1]
left foot
The single-arm / open-label design suffers from limitations such as possible bias in patient selection and outcome assessment. However, adverse events were adjudicated by the DSMB. Small trial size warrants caution; further studies are necessary.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The study PI will submit the manuscript of any proposed publication to the sponsor at least 45 days before publication, and the sponsor shall have the right to review and comment upon the publication. The sponsor shall provide any comments to investigator within 30 days of receipt of the proposed publication or presentation. At the end of the 30 day period, the PI shall be free to proceed with the publication or presentation provided he or she has complied with the sponsor's feedback.
Results Point of Contact
Name/Title: Sean I. Savitz, MD
Organization: University of Texas Health Science Center at Houston
Phone: 713-500-7083
Responsible Party: Sean Savitz, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01183533     History of Changes
Other Study ID Numbers: HSC-MS-10-0195
First Submitted: August 16, 2010
First Posted: August 17, 2010
Results First Submitted: October 28, 2014
Results First Posted: November 25, 2014
Last Update Posted: November 25, 2014