The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH \< 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
500
1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic, Arizona
Phoenix, Arizona, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
University of Southern California - Keck School of Medicine
Los Angeles, California, United States
University of California Los Angeles
Los Angeles, California, United States
Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis
Analysis modified on September 29, 2015 to account for adaptive randomization. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3
Comparing longitudinal modified Rankin Scale (mRS) scores 0-3 at Day 30 and Day 180. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 30 days and 180 days
All Cause Mortality
Time frame: 180 days
Clot Removal (Amount of Residual Blood)
Change in blood volume measured between stability scan and end of treatment scan
Time frame: 72 hours
Intensity of Critical Care Management - Hospital Days
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - ICU Days
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - ICP Management
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - Mechanical Ventilation
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - Pressors
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
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Stanford University
Palo Alto, California, United States
Hartford Hospital
Hartford, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
Mayo Clinic, Jacksonville
Jacksonville, Florida, United States
...and 71 more locations
Time frame: 30 days
Intensity of Critical Care Management - Shunts
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - All Infections
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - Pneumonia
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 30 days
Intensity of Critical Care Management - All Infections
Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP \>20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
Time frame: 180 days
Safety/Mortality - Mortality Within 30 Days
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Time frame: 30 days
Safety/Mortality - Bacterial Brain Infections Within 30 Days
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Time frame: 30 days
Safety/Mortality - Systematic Bleeds Within 72 Hours
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Time frame: 72 hours
Safety/Mortality - Systematic Bleeds Within 30 Days
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Time frame: 30 days
Adverse and Serious Adverse Events
Assessment of number of adverse and serious adverse events by treatment group.
Time frame: 180 days
Predicting Hazards of Death by Treatment Group
Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American)
Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White)
Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic)
Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
Time frame: 180 days
Functional Status - Barthel Index
Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The Barthel Index (BI) assesses ten functional tasks of daily living, and each task provides a measure for level of independence. Scores range from 0 and 100, with a higher score indicating greater independence.
Time frame: 180 days
Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability
Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The extended Glasgow Outcome Scale (eGOS) is a global scale for functional outcome with eight categories: 1 - Death, 2 - Vegetative State, 3 - Lower Severe Disability, 4 - Upper Severe Disability, 5 - Lower Moderate Disability, 6 - Upper Moderate Disability, 7 - Lower Good Recovery, 8 - Upper Good Recovery.
Time frame: 180 days
Functional Status - National Institutes of Health Stroke Scale (NIHSS)
Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The National Institutes of Health Stroke Scale (NIHSS) is a 15-item scale that assesses language, motor function, sensory loss, consciousness, visual fields, extraocular movements, coordination, neglect, and speech. It is scored from 0 (no stroke symptoms) to 42 (severe stroke).
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Strength
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Mobility
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Hand Function
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Communication
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Thinking
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Emotion
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Participation
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Recovery
Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.
Time frame: 180 days
Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS)
Assessment of SIS and EuroQol Visual Analog Scale by group. EuroQol Visual Analogue Scale (EQ-VAS) is a self-reported measure of health status. It is a marked scale where individuals draw a line to indicate their health, with end points of 0 (the worst health you can imagine) and 100 (the best health you can imagine).
Time frame: 180 days