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Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Phase 3
Completed
Conditions
Intraventricular Hemorrhage
Interventions
Other: Normal saline
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
GroupInterventionDescription
Saline PlaceboNormal saline1 ml of normal saline administered via the intraventricular catheter
AlteplaseAlteplaseadministration of alteplase via the intraventricular catheter
Primary Outcome Measures
NameTimeMethod
Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis180 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 Analysis180 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 Analysis180 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) <= 3180 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) <=330 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
NameTimeMethod
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 Mortality180 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 Days30 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 Days30 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 Management30 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 Ventilation30 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 - Pressors30 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 - Shunts30 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 Infections180 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 - Pneumonia30 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 Days30 days

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Safety/Mortality - Bacterial Brain Infections Within 30 Days30 days

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Safety/Mortality - Systematic Bleeds Within 72 Hours72 hours

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Safety/Mortality - Systematic Bleeds Within 30 Days30 days

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Adverse and Serious Adverse Events180 days

Assessment of number of adverse and serious adverse events by treatment group.

Predicting Hazards of Death by Treatment Group180 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) - Thinking180 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) - Emotion180 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) - Participation180 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) - Recovery180 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 Index180 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 Disability180 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) - Strength180 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) - Mobility180 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 Function180 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 Living180 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) - Communication180 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

🇺🇸

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

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