Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III)

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 Overview

• Status: Completed
• Conditions: Intraventricular Hemorrhage
• Intervention / Treatment: Drug: Alteplase; Other: Normal saline

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clínicas de Porto Alegre
  • Porto Alegre, Brazil
    • Hospital de Pronto Socorro de Porto Alegre
  • Ribeirão Preto, Brazil, 14015-130
    • Hospital de Clínicas de Ribeirão Preto
  • Sao Paulo, Brazil, 04039032
    • Hospital Sao Paulo Universidade Federal de Sao Paulo / UNIFESP
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89202165
      • Hospital Sao Jose, Joinville
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute at McGill University
• Germany
  • Erlangen, Germany, 91054
    • University of Erlangen
  • Halle, Germany, D-06120
    • University of Halle
  • Heidelberg, Germany, 69120
    • University of Heidelberg
  • Leipzig, Germany, 04103
    • University of Leipzig
  • Mainz, Germany, D-55131
    • University of Mainz
  • Tübingen, Germany, 72076
    • University of Tubingen
• Hungary
  • Budapest, Hungary, 1134
    • Honved Korhaz
  • Debrecen, Hungary, 4032
    • University of Debrecen
  • Pecs, Hungary, 7623
    • University of Pecs
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • University of Szeged
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Hospital
  • Ramat-Gan, Israel, 52621
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Vall D'Hebron University Hospital
  • Barcelona, Spain, 08015
    • Bellvitge Hospital
• Switzerland
  • Bern, Switzerland
    • University Hospital, Inselpital, Bern
  • ZH
    • Zurich, ZH, Switzerland, CH-8091
      • University of Zurich
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE4 6BE
    • Newcastle General Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University of Southampton Hospital
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic, Arizona
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90089
      • University of Southern California - Keck School of Medicine
    • Palo Alto, California, United States, 94034
      • Stanford University
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06520-8018
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Jacksonville
    • Sarasota, Florida, United States, 34232
      • Intercoastal Medical Center
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Ruan Neurology Clinical and Research Center
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21230
      • Johns Hopkins University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Brain and Stroke Institute
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University
    • Springfield, Missouri, United States, 65804
      • Springfield Neurological and Spine Institute
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
    • Edison, New Jersey, United States, 08818
      • New Jersey Neuroscience Institute at JFK
  • New York
    • Buffalo, New York, United States, 14203
      • University of Buffalo
    • Manhasset, New York, United States, 11030
      • Northshore University Hospital Long Island
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case-Western Reserve University Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 04102
      • Maine Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Stroke Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas, Southwestern, Dallas
    • Houston, Texas, United States, 77030
      • University of Texas, Houston
    • San Antonio, Texas, United States, 78229
      • University of Texas, San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alteplase; administration of alteplase via the intraventricular catheter	Drug: Alteplase; 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses; Other Names: Cathflo Activase; rt-PA
Placebo Comparator: Saline Placebo; 1 ml of normal saline administered via the intraventricular catheter	Other: Normal saline; 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Genentech, Inc.; Emissary International LLC
• Investigators: Study Chair: Daniel F. Hanley, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Roh DJ, Asonye IS, Carvalho Poyraz F, Magid-Bernstein JR, Joiner EF, Avadhani R, Awad I, Hanley DF, Ziai WC, Murthy SB. Intraventricular Hemorrhage Expansion in the CLEAR III Trial: A Post Hoc Exploratory Analysis. Stroke. 2022 Jun;53(6):1847-1853. doi: 10.1161/STROKEAHA.121.037438. Epub 2022 Jan 28.
• Hansen BM, Ullman N, Muschelli J, Norrving B, Dlugash R, Avadhani R, Awad I, Zuccarello M, Ziai WC, Hanley DF, Thompson RE, Lindgren A; MISTIE and CLEAR Investigators. Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III. Neurocrit Care. 2020 Oct;33(2):516-524. doi: 10.1007/s12028-020-00916-4.
• Porter AL, Ebot J, Lane K, Mooney LH, Lannen AM, Richie EM, Dlugash R, Mayo S, Brott TG, Ziai W, Freeman WD, Hanley DF. Enhancing the Informed Consent Process Using Shared Decision Making and Consent Refusal Data from the CLEAR III Trial. Neurocrit Care. 2020 Feb;32(1):340-347. doi: 10.1007/s12028-019-00860-y.
• Eslami V, Tahsili-Fahadan P, Rivera-Lara L, Gandhi D, Ali H, Parry-Jones A, Nelson LS, Thompson RE, Nekoobakht-Tak S, Dlugash R, McBee N, Awad I, Hanley DF, Ziai WC. Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage. Stroke. 2019 Jul;50(7):1688-1695. doi: 10.1161/STROKEAHA.118.024187. Epub 2019 Jun 10.
• Fam MD, Zeineddine HA, Eliyas JK, Stadnik A, Jesselson M, McBee N, Lane K, Cao Y, Wu M, Zhang L, Thompson RE, John S, Ziai W, Hanley DF, Awad IA; CLEAR III Trial Investigators. CSF inflammatory response after intraventricular hemorrhage. Neurology. 2017 Oct 10;89(15):1553-1560. doi: 10.1212/WNL.0000000000004493. Epub 2017 Sep 8.
• Hanley DF, Lane K, McBee N, Ziai W, Tuhrim S, Lees KR, Dawson J, Gandhi D, Ullman N, Mould WA, Mayo SW, Mendelow AD, Gregson B, Butcher K, Vespa P, Wright DW, Kase CS, Carhuapoma JR, Keyl PM, Diener-West M, Muschelli J, Betz JF, Thompson CB, Sugar EA, Yenokyan G, Janis S, John S, Harnof S, Lopez GA, Aldrich EF, Harrigan MR, Ansari S, Jallo J, Caron JL, LeDoux D, Adeoye O, Zuccarello M, Adams HP Jr, Rosenblum M, Thompson RE, Awad IA; CLEAR III Investigators. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017 Feb 11;389(10069):603-611. doi: 10.1016/S0140-6736(16)32410-2. Epub 2017 Jan 10.
• Webb AJ, Ullman NL, Morgan TC, Muschelli J, Kornbluth J, Awad IA, Mayo S, Rosenblum M, Ziai W, Zuccarrello M, Aldrich F, John S, Harnof S, Lopez G, Broaddus WC, Wijman C, Vespa P, Bullock R, Haines SJ, Cruz-Flores S, Tuhrim S, Hill MD, Narayan R, Hanley DF; MISTIE and CLEAR Investigators. Accuracy of the ABC/2 Score for Intracerebral Hemorrhage: Systematic Review and Analysis of MISTIE, CLEAR-IVH, and CLEAR III. Stroke. 2015 Sep;46(9):2470-6. doi: 10.1161/STROKEAHA.114.007343. Epub 2015 Aug 4.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 31, 2008
• First Submitted That Met QC Criteria: October 31, 2008
• First Posted (Estimate): November 2, 2008

Study Record Updates

• Last Update Posted (Actual): December 5, 2018
• Last Update Submitted That Met QC Criteria: November 9, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: intraventricular hemorrhage thrombolysis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: IVH06; 5U01NS062851-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Data repository-VISTA
   Information identifier: Data repository-VISTA
   Information comments: when available
2. Study Protocol
   Information comments: when available
3. Statistical Analysis Plan
   Information comments: when available