Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
CLEAR III
2 other identifiers
interventional
500
9 countries
81
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2009
Longer than P75 for phase_3
81 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 31, 2008
CompletedFirst Posted
Study publicly available on registry
November 3, 2008
CompletedStudy Start
First participant enrolled
July 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedResults Posted
Study results publicly available
July 2, 2017
CompletedDecember 5, 2018
November 1, 2018
6 years
October 31, 2008
March 30, 2017
November 9, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
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 Outcomes (41)
All Cause Mortality
180 days
Clot Removal (Amount of Residual Blood)
72 hours
Intensity of Critical Care Management - Hospital Days
30 days
Intensity of Critical Care Management - ICU Days
30 days
Intensity of Critical Care Management - ICP Management
30 days
- +36 more secondary outcomes
Study Arms (2)
Alteplase
EXPERIMENTALadministration of alteplase via the intraventricular catheter
Saline Placebo
PLACEBO COMPARATOR1 ml of normal saline administered via the intraventricular catheter
Interventions
1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Johns Hopkins Universitylead
- National Institute of Neurological Disorders and Stroke (NINDS)collaborator
- Genentech, Inc.collaborator
- Emissary International LLCcollaborator
Study Sites (81)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Mayo Clinic, Arizona
Phoenix, Arizona, 85054, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
University of Southern California - Keck School of Medicine
Los Angeles, California, 90089, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
Stanford University
Palo Alto, California, 94034, United States
Hartford Hospital
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520-8018, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224, United States
Intercoastal Medical Center
Sarasota, Florida, 34232, United States
University of South Florida
Tampa, Florida, 33606, United States
Rush University
Chicago, Illinois, 60612, United States
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
University of Chicago
Chicago, Illinois, 60637, United States
Ruan Neurology Clinical and Research Center
Des Moines, Iowa, 50314, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Kansas University Medical Center
Kansas City, Kansas, 66160, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Johns Hopkins University
Baltimore, Maryland, 21230, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
St. Luke's Brain and Stroke Institute
Kansas City, Missouri, 64111, United States
Springfield Neurological and Spine Institute
Springfield, Missouri, 65804, United States
St. Louis University
St Louis, Missouri, 63104, United States
Cooper University Hospital
Camden, New Jersey, 08103, United States
New Jersey Neuroscience Institute at JFK
Edison, New Jersey, 08818, United States
University of Buffalo
Buffalo, New York, 14203, United States
Northshore University Hospital Long Island
Manhasset, New York, 11030, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Columbia University
New York, New York, 10032, United States
SUNY Upstate Medical Center
Syracuse, New York, 13210, United States
Wake Forest University
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati
Cincinnati, Ohio, 45219, United States
Case-Western Reserve University Hospital
Cleveland, Ohio, 44106, United States
Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Maine Medical Center
Portland, Oregon, 04102, United States
Providence Stroke Center
Portland, Oregon, 97225, United States
Abington Memorial Hospital
Abington, Pennsylvania, 19001, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt
Nashville, Tennessee, 37232, United States
University of Texas, Southwestern, Dallas
Dallas, Texas, 75390, United States
University of Texas, Houston
Houston, Texas, 77030, United States
University of Texas, San Antonio
San Antonio, Texas, 78229, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital Sao Jose, Joinville
Joinville, Santa Catarina, 89202165, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, 90035-903, Brazil
Hospital de Pronto Socorro de Porto Alegre
Porto Alegre, Brazil
Hospital de Clinicas de Ribeirao Preto
Ribeirão Preto, 14015-130, Brazil
Hospital Sao Paulo Universidade Federal de Sao Paulo / UNIFESP
São Paulo, 04039032, Brazil
University of Alberta
Edmonton, Alberta, T6G 2B7, Canada
Montreal Neurological Institute at McGill University
Montreal, Quebec, H3A 2B4, Canada
University of Erlangen
Erlangen, 91054, Germany
University of Halle
Halle, D-06120, Germany
University of Heidelberg
Heidelberg, 69120, Germany
University of Leipzig
Leipzig, 04103, Germany
University of Mainz
Mainz, D-55131, Germany
University of Tubingen
Tübingen, 72076, Germany
University of Szeged
Szeged, Csongrád megye, 6725, Hungary
Honved Korhaz
Budapest, 1134, Hungary
University of Debrecen
Debrecen, 4032, Hungary
University of Pecs
Pécs, 7623, Hungary
Rambam Medical Center
Haifa, 31096, Israel
Hadassah Hebrew University Hospital
Jerusalem, 91120, Israel
Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Sourasky Medical Center
Tel Aviv, 64239, Israel
Bellvitge Hospital
Barcelona, 08015, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025, Spain
Vall d'Hebron University Hospital
Barcelona, 08035, Spain
University of Zurich
Zurich, Canton of Zurich, CH-8091, Switzerland
University Hospital, Inselpital, Bern
Bern, Switzerland
Salford Royal NHS Foundation Trust
Salford, Manchester, M6 8HD, United Kingdom
Newcastle General Hospital
Newcastle upon Tyne, NE4 6BE, United Kingdom
University of Southampton Hospital
Southampton, SO16 6YD, United Kingdom
Related Publications (7)
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.
PMID: 35086362DERIVEDHansen 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.
PMID: 32026447DERIVEDPorter 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.
PMID: 31571176DERIVEDEslami 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.
PMID: 31177984DERIVEDFam 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.
PMID: 28887375DERIVEDHanley 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.
PMID: 28081952DERIVEDWebb 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.
PMID: 26243227DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Daniel F. Hanley
- Organization
- Johns Hopkins University Division of Brain Injury Outcomes
Study Officials
- STUDY CHAIR
Daniel F. Hanley, MD
Johns Hopkins University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 31, 2008
First Posted
November 3, 2008
Study Start
July 1, 2009
Primary Completion
July 1, 2015
Study Completion
January 1, 2016
Last Updated
December 5, 2018
Results First Posted
July 2, 2017
Record last verified: 2018-11
Data Sharing
- IPD Sharing
- Will not share