Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Phase 3

Completed

Conditions: Intraventricular Hemorrhage

Interventions: Other: Normal saline
Drug: Alteplase

Registration Number: NCT00784134

Lead Sponsor: Johns Hopkins University

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 500

Inclusion Criteria

Age 18-80
Symptom onset less than 24 hrs prior to diagnostic CT scan
Spontaneous ICH less than or equal to 30 cc or primary IVH
IVH obstructing 3rd and/or 4th ventricles
ICH clot stability at 6 hours or more post IVC placement
IVH clot stability at 6 hours or more post IVC placement
Catheter tract bleeding stability 6 hours or more post IVC placement
EVD placed per standard medical care
SBP less than 200 mmHg sustained for 6 hours prior to drug administration
Able to randomize within 72 hours of diagnostic CT scan
Historical Rankin of 0 or 1

Exclusion Criteria

Suspected or untreated ruptured cerebral aneurysm, AVM, or tumor
Presence of a choroid plexus vascular malformation or Moyamoya
Clotting disorders
Platelet count less than 100,000, INR greater than 1.4
Pregnancy
Infratentorial hemorrhage
SAH at clinical presentation
ICH/IVH enlargement that cannot be stabilized in the treatment time window
Ongoing internal bleeding
Superficial or surface bleeding
Prior enrollment in the study
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
Planned or simultaneous participation (between screening and Day-30) in another interventional medical investigation or clinical trial.
No subject or legal representative to give written informed consent

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline Placebo	Normal saline	1 ml of normal saline administered via the intraventricular catheter
Alteplase	Alteplase	administration of alteplase via the intraventricular catheter

Primary Outcome Measures

Name	Time	Method
Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis	180 days	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).
Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis	180 days	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).
Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis	180 days	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).
Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3	180 days	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).
Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3	30 days and 180 days	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).

Secondary Outcome Measures

Name	Time	Method
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic)	180 days	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).
All Cause Mortality	180 days
Clot Removal (Amount of Residual Blood)	72 hours	Change in blood volume measured between stability scan and end of treatment scan
Intensity of Critical Care Management - Hospital Days	30 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.
Intensity of Critical Care Management - ICU Days	30 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.
Intensity of Critical Care Management - ICP Management	30 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.
Intensity of Critical Care Management - Mechanical Ventilation	30 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.
Intensity of Critical Care Management - Pressors	30 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.
Intensity of Critical Care Management - Shunts	30 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.
Intensity of Critical Care Management - All Infections	180 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.
Intensity of Critical Care Management - Pneumonia	30 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.
Safety/Mortality - Mortality Within 30 Days	30 days	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Safety/Mortality - Bacterial Brain Infections Within 30 Days	30 days	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Safety/Mortality - Systematic Bleeds Within 72 Hours	72 hours	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Safety/Mortality - Systematic Bleeds Within 30 Days	30 days	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Adverse and Serious Adverse Events	180 days	Assessment of number of adverse and serious adverse events by treatment group.
Predicting Hazards of Death by Treatment Group	180 days	Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml)	180 days	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).
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic)	180 days	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).
Quality of Life - Stroke Impact Scale (SIS) - Thinking	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Emotion	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Participation	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Recovery	180 days	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.
Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS)	180 days	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).
Functional Status - Barthel Index	180 days	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.
Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability	180 days	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.
Functional Status - National Institutes of Health Stroke Scale (NIHSS)	180 days	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).
Quality of Life - Stroke Impact Scale (SIS) - Strength	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Mobility	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Hand Function	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living	180 days	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.
Quality of Life - Stroke Impact Scale (SIS) - Communication	180 days	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.

Trial Locations

Locations (81): 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
Stanford University
🇺🇸
Palo Alto, California, United States
Hartford Hospital
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Hartford, Connecticut, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Georgetown University
🇺🇸
Washington, District of Columbia, United States
Mayo Clinic, Jacksonville
🇺🇸
Jacksonville, Florida, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States