Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Intraventricular Hemorrhage Clinical Trial

— CLEAR III  

Official title:

Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00784134
• Other study ID #: IVH06
• Secondary ID: 5U01NS062851-05
• Status: Completed
• Phase: Phase 3
• Start date: July 2009
• Est. completion date: January 2016

Study information

• Verified date: November 2018
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: January 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intraventricular Hemorrhage

Intervention

Drug:
• Alteplase
1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses

Other:
• Normal saline
1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses

Locations

Country	Name	City	State
Brazil	Hospital Sao Jose, Joinville	Joinville	Santa Catarina
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Brazil	Hospital de Pronto Socorro de Porto Alegre	Porto Alegre
Brazil	Hospital de Clinicas de Ribeirao Preto	Ribeirão Preto
Brazil	Hospital Sao Paulo Universidade Federal de Sao Paulo / UNIFESP	Sao Paulo
Canada	University of Alberta	Edmonton	Alberta
Canada	Montreal Neurological Institute at McGill University	Montreal	Quebec
Germany	University of Erlangen	Erlangen
Germany	University of Halle	Halle
Germany	University of Heidelberg	Heidelberg
Germany	University of Leipzig	Leipzig
Germany	University of Mainz	Mainz
Germany	University of Tubingen	Tübingen
Hungary	Honved Korhaz	Budapest
Hungary	University of Debrecen	Debrecen
Hungary	University of Pecs	Pecs
Hungary	University of Szeged	Szeged	Csongrad
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Hebrew University Hospital	Jerusalem
Israel	Chaim Sheba Medical Center	Ramat-Gan
Israel	Sourasky Medical Center	Tel Aviv
Spain	Bellvitge Hospital	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Vall d'Hebron University Hospital	Barcelona
Switzerland	University Hospital, Inselpital, Bern	Bern
Switzerland	University of Zurich	Zurich	ZH
United Kingdom	Newcastle General Hospital	Newcastle upon Tyne
United Kingdom	Salford Royal NHS Foundation Trust	Salford	Manchester
United Kingdom	University of Southampton Hospital	Southampton
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Buffalo	Buffalo	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case-Western Reserve University Hospital	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	University of Texas, Southwestern, Dallas	Dallas	Texas
United States	Ruan Neurology Clinical and Research Center	Des Moines	Iowa
United States	Henry Ford Health System	Detroit	Michigan
United States	New Jersey Neuroscience Institute at JFK	Edison	New Jersey
United States	Hartford Hospital	Hartford	Connecticut
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Texas, Houston	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic, Jacksonville	Jacksonville	Florida
United States	Kansas University Medical Center	Kansas City	Kansas
United States	St. Luke's Brain and Stroke Institute	Kansas City	Missouri
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	University of Southern California - Keck School of Medicine	Los Angeles	California
United States	Northshore University Hospital Long Island	Manhasset	New York
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Stanford University	Palo Alto	California
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic, Arizona	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Oregon
United States	Providence Stroke Center	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	St. Louis University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Texas, San Antonio	San Antonio	Texas
United States	Intercoastal Medical Center	Sarasota	Florida
United States	Springfield Neurological and Spine Institute	Springfield	Missouri
United States	SUNY Upstate Medical Center	Syracuse	New York
United States	University of South Florida	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Johns Hopkins University	Emissary International LLC, Genentech, Inc., National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Germany,  Hungary,  Israel,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	180 days
Primary	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).	180 days
Primary	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).	180 days
Primary	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).	180 days
Primary	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).	30 days and 180 days
Secondary	All Cause Mortality		180 days
Secondary	Clot Removal (Amount of Residual Blood)	Change in blood volume measured between stability scan and end of treatment scan	72 hours
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	30 days
Secondary	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.	180 days
Secondary	Safety/Mortality - Mortality Within 30 Days	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.	30 days
Secondary	Safety/Mortality - Bacterial Brain Infections Within 30 Days	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.	30 days
Secondary	Safety/Mortality - Systematic Bleeds Within 72 Hours	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.	72 hours
Secondary	Safety/Mortality - Systematic Bleeds Within 30 Days	Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.	30 days
Secondary	Adverse and Serious Adverse Events	Assessment of number of adverse and serious adverse events by treatment group.	180 days
Secondary	Predicting Hazards of Death by Treatment Group	Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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).	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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).	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	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).	180 days

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