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

• ClinicalTrials.gov Identifier: NCT00784134
• Recruitment Status: Completed
• First Posted: November 2, 2008
• Results First Posted: July 2, 2017
• Last Update Posted: December 5, 2018
• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Genentech, Inc.; Emissary International LLC
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Intraventricular Hemorrhage	Drug: Alteplase; Other: Normal saline	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
• Study Start Date: July 2009
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: January 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis [ Time Frame: 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).
2. Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis [ Time Frame: 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).
3. Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis [ Time Frame: 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).
4. Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3 [ Time Frame: 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).
5. Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3 [ Time Frame: 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 :

1. All Cause Mortality [ Time Frame: 180 days ]
2. Clot Removal (Amount of Residual Blood) [ Time Frame: 72 hours ]
   Change in blood volume measured between stability scan and end of treatment scan
3. Intensity of Critical Care Management - Hospital Days [ Time Frame: 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.
4. Intensity of Critical Care Management - ICU Days [ Time Frame: 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.
5. Intensity of Critical Care Management - ICP Management [ Time Frame: 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.
6. Intensity of Critical Care Management - Mechanical Ventilation [ Time Frame: 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.
7. Intensity of Critical Care Management - Pressors [ Time Frame: 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.
8. Intensity of Critical Care Management - Shunts [ Time Frame: 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.
9. Intensity of Critical Care Management - All Infections [ Time Frame: 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.
10. Intensity of Critical Care Management - Pneumonia [ Time Frame: 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.
11. Intensity of Critical Care Management - All Infections [ Time Frame: 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.
12. Safety/Mortality - Mortality Within 30 Days [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
13. Safety/Mortality - Bacterial Brain Infections Within 30 Days [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
14. Safety/Mortality - Systematic Bleeds Within 72 Hours [ Time Frame: 72 hours ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
15. Safety/Mortality - Systematic Bleeds Within 30 Days [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
16. Adverse and Serious Adverse Events [ Time Frame: 180 days ]
    Assessment of number of adverse and serious adverse events by treatment group.
17. Predicting Hazards of Death by Treatment Group [ Time Frame: 180 days ]
    Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.
18. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American) [ Time Frame: 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).
19. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White) [ Time Frame: 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).
20. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female) [ Time Frame: 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).
21. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male) [ Time Frame: 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).
22. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under) [ Time Frame: 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).
23. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years) [ Time Frame: 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).
24. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml) [ Time Frame: 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).
25. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml) [ Time Frame: 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).
26. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml) [ Time Frame: 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).
27. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic) [ Time Frame: 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).
28. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic) [ Time Frame: 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).
29. Functional Status - Barthel Index [ Time Frame: 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.
30. Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability [ Time Frame: 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.
31. Functional Status - National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 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).
32. Quality of Life - Stroke Impact Scale (SIS) - Strength [ Time Frame: 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.
33. Quality of Life - Stroke Impact Scale (SIS) - Mobility [ Time Frame: 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.
34. Quality of Life - Stroke Impact Scale (SIS) - Hand Function [ Time Frame: 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.
35. Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living [ Time Frame: 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.
36. Quality of Life - Stroke Impact Scale (SIS) - Communication [ Time Frame: 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.
37. Quality of Life - Stroke Impact Scale (SIS) - Thinking [ Time Frame: 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.
38. Quality of Life - Stroke Impact Scale (SIS) - Emotion [ Time Frame: 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.
39. Quality of Life - Stroke Impact Scale (SIS) - Participation [ Time Frame: 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.
40. Quality of Life - Stroke Impact Scale (SIS) - Recovery [ Time Frame: 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.
41. Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS) [ Time Frame: 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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Arizona

Mayo Clinic, Arizona

Phoenix, Arizona, United States, 85054

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

University of Southern California - Keck School of Medicine

Los Angeles, California, United States, 90089

University of California Los Angeles

Los Angeles, California, United States, 90095

Stanford University

Palo Alto, California, United States, 94034

United States, Connecticut

Hartford Hospital

Hartford, Connecticut, United States, 06106

Yale University

New Haven, Connecticut, United States, 06520-8018

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20007

United States, Florida

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States, 32224

Intercoastal Medical Center

Sarasota, Florida, United States, 34232

University of South Florida

Tampa, Florida, United States, 33606

United States, Illinois

Rush University

Chicago, Illinois, United States, 60612

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

University of Chicago

Chicago, Illinois, United States, 60637

United States, Iowa

Ruan Neurology Clinical and Research Center

Des Moines, Iowa, United States, 50314

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kansas

Kansas University Medical Center

Kansas City, Kansas, United States, 66160

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

Johns Hopkins University

Baltimore, Maryland, United States, 21230

United States, Michigan

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Missouri

St. Luke's Brain and Stroke Institute

Kansas City, Missouri, United States, 64111

St. Louis University

Saint Louis, Missouri, United States, 63104

Springfield Neurological and Spine Institute

Springfield, Missouri, United States, 65804

United States, New Jersey

Cooper University Hospital

Camden, New Jersey, United States, 08103

New Jersey Neuroscience Institute at JFK

Edison, New Jersey, United States, 08818

United States, New York

University of Buffalo

Buffalo, New York, United States, 14203

Northshore University Hospital Long Island

Manhasset, New York, United States, 11030

Mount Sinai Hospital

New York, New York, United States, 10029

Columbia University

New York, New York, United States, 10032

SUNY Upstate Medical Center

Syracuse, New York, United States, 13210

United States, North Carolina

Wake Forest University

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45219

Case-Western Reserve University Hospital

Cleveland, Ohio, United States, 44106

Ohio State University Medical Center

Columbus, Ohio, United States, 43210

United States, Oregon

Maine Medical Center

Portland, Oregon, United States, 04102

Providence Stroke Center

Portland, Oregon, United States, 97225

United States, Pennsylvania

Abington Memorial Hospital

Abington, Pennsylvania, United States, 19001

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

Temple University Hospital

Philadelphia, Pennsylvania, United States, 19140

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States, 19141

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Tennessee

Vanderbilt

Nashville, Tennessee, United States, 37232

United States, Texas

University of Texas, Southwestern, Dallas

Dallas, Texas, United States, 75390

University of Texas, Houston

Houston, Texas, United States, 77030

University of Texas, San Antonio

San Antonio, Texas, United States, 78229

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

United States, Virginia

Virginia Commonwealth University

Richmond, Virginia, United States, 23298

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Brazil

Hospital Sao Jose, Joinville

Joinville, Santa Catarina, Brazil, 89202165

Hospital de Clinicas de Porto Alegre

Porto Alegre, Brazil, 90035-903

Hospital de Pronto Socorro de Porto Alegre

Porto Alegre, Brazil

Hospital de Clinicas de Ribeirao Preto

Ribeirão Preto, Brazil, 14015-130

Hospital Sao Paulo Universidade Federal de Sao Paulo / UNIFESP

Sao Paulo, Brazil, 04039032

Canada, Alberta

University of Alberta

Edmonton, Alberta, Canada, T6G 2B7

Canada, Quebec

Montreal Neurological Institute at McGill University

Montreal, Quebec, Canada, H3A 2B4

Germany

University of Erlangen

Erlangen, Germany, 91054

University of Halle

Halle, Germany, D-06120

University of Heidelberg

Heidelberg, Germany, 69120

University of Leipzig

Leipzig, Germany, 04103

University of Mainz

Mainz, Germany, D-55131

University of Tubingen

Tübingen, Germany, 72076

Hungary

University of Szeged

Szeged, Csongrad, Hungary, 6725

Honved Korhaz

Budapest, Hungary, 1134

University of Debrecen

Debrecen, Hungary, 4032

University of Pecs

Pecs, Hungary, 7623

Israel

Rambam Medical Center

Haifa, Israel, 31096

Hadassah Hebrew University Hospital

Jerusalem, Israel, 91120

Chaim Sheba Medical Center

Ramat-Gan, Israel, 52621

Sourasky Medical Center

Tel Aviv, Israel, 64239

Spain

Bellvitge Hospital

Barcelona, Spain, 08015

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08025

Vall d'Hebron University Hospital

Barcelona, Spain, 08035

Switzerland

University of Zurich

Zurich, ZH, Switzerland, CH-8091

University Hospital, Inselpital, Bern

Bern, Switzerland

United Kingdom

Salford Royal NHS Foundation Trust

Salford, Manchester, United Kingdom, M6 8HD

Newcastle General Hospital

Newcastle upon Tyne, United Kingdom, NE4 6BE

University of Southampton Hospital

Southampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

Johns Hopkins University

National Institute of Neurological Disorders and Stroke (NINDS)

Genentech, Inc.

Emissary International LLC

Investigators

• Study Chair: Daniel F. Hanley, MD; Johns Hopkins University

More Information

Additional Information:

Related Info 

Study Data/Documents: Data repository-VISTA 

Identifier: Data repository-VISTA
when available

Study Protocol 

when available

Statistical Analysis Plan 

when available

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00784134
• Other Study ID Numbers: IVH06; 5U01NS062851-05 ( U.S. NIH Grant/Contract )
• First Posted: November 2, 2008
• Results First Posted: July 2, 2017
• Last Update Posted: December 5, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Johns Hopkins University:

intraventricular hemorrhage thrombolysis

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Intracranial Hemorrhages; Pathologic Processes; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Tissue Plasminogen Activator; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action