Intraventricular HemorrhagePhase 3CLEAR IIINCT00784134
Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
A Phase 3 study testing Alteplase and Normal saline in people with Intraventricular Hemorrhage, run by Johns Hopkins University at 81 sites in 9 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Intraventricular Hemorrhage
- What is being tested?
- Alteplase and Normal saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 81 sitesin 9 countries
- Study dates
- Jul 2009to Jan 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
81 sites in 9 countries.
81 sites in 9 countries
United States52 sites
Abington Memorial Hospital
Abington, Pennsylvania, 19001
University of Maryland
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21230
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of Buffalo
Buffalo, New York, 14203
Cooper University Hospital
Camden, New Jersey, 08103
Medical University of South Carolina
Charleston, South Carolina, 29425
Rush University
Chicago, Illinois, 60612
University of Illinois at Chicago
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45219
Case-Western Reserve University Hospital
Cleveland, Ohio, 44106
Ohio State University Medical Center
Columbus, Ohio, 43210
University of Texas, Southwestern, Dallas
Dallas, Texas, 75390
Ruan Neurology Clinical and Research Center
Des Moines, Iowa, 50314
Henry Ford Health System
Detroit, Michigan, 48202
New Jersey Neuroscience Institute at JFK
Edison, New Jersey, 08818
Hartford Hospital
Hartford, Connecticut, 06106
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Texas, Houston
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224
Kansas University Medical Center
Kansas City, Kansas, 66160
St. Luke's Brain and Stroke Institute
Kansas City, Missouri, 64111
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Southern California - Keck School of Medicine
Los Angeles, California, 90089
University of California Los Angeles
Los Angeles, California, 90095
Northshore University Hospital Long Island
Manhasset, New York, 11030
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt
Nashville, Tennessee, 37232
Yale University
New Haven, Connecticut, 06520-8018
Mount Sinai Hospital
New York, New York, 10029
Columbia University
New York, New York, 10032
Stanford University
Palo Alto, California, 94034
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Mayo Clinic, Arizona
Phoenix, Arizona, 85054
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Maine Medical Center
Portland, Oregon, 04102
Providence Stroke Center
Portland, Oregon, 97225
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Utah
Salt Lake City, Utah, 84132
University of Texas, San Antonio
San Antonio, Texas, 78229
Intercoastal Medical Center
Sarasota, Florida, 34232
Springfield Neurological and Spine Institute
Springfield, Missouri, 65804
St. Louis University
St Louis, Missouri, 63104
SUNY Upstate Medical Center
Syracuse, New York, 13210
University of South Florida
Tampa, Florida, 33606
Georgetown University
Washington D.C., District of Columbia, 20007
Wake Forest University
Winston-Salem, North Carolina, 27157
Germany6 sites
University of Erlangen
Erlangen, 91054
University of Halle
Halle, D-06120
University of Heidelberg
Heidelberg, 69120
University of Leipzig
Leipzig, 04103
University of Mainz
Mainz, D-55131
University of Tubingen
Tübingen, 72076
Brazil5 sites
Hospital Sao Jose, Joinville
Joinville, Santa Catarina, 89202165
Hospital de Clinicas de Porto Alegre
Porto Alegre, 90035-903
Hospital de Pronto Socorro de Porto Alegre
Porto Alegre
Hospital de Clinicas de Ribeirao Preto
Ribeirão Preto, 14015-130
Hospital Sao Paulo Universidade Federal de Sao Paulo / UNIFESP
São Paulo, 04039032
Hungary4 sites
Honved Korhaz
Budapest, 1134
University of Debrecen
Debrecen, 4032
University of Pecs
Pécs, 7623
University of Szeged
Szeged, Csongrád megye, 6725
Israel4 sites
Rambam Medical Center
Haifa, 31096
Hadassah Hebrew University Hospital
Jerusalem, 91120
Chaim Sheba Medical Center
Ramat Gan, 52621
Sourasky Medical Center
Tel Aviv, 64239
Spain3 sites
Bellvitge Hospital
Barcelona, 08015
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Vall d'Hebron University Hospital
Barcelona, 08035
United Kingdom3 sites
Newcastle General Hospital
Newcastle upon Tyne, NE4 6BE
Salford Royal NHS Foundation Trust
Salford, Manchester, M6 8HD
University of Southampton Hospital
Southampton, SO16 6YD
Canada2 sites
University of Alberta
Edmonton, Alberta, T6G 2B7
Montreal Neurological Institute at McGill University
Montreal, Quebec, H3A 2B4
Switzerland2 sites
University Hospital, Inselpital, Bern
Bern
University of Zurich
Zurich, Canton of Zurich, CH-8091
About this study
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).
- Conditions
- Intraventricular Hemorrhage
- Being tested
- Alteplase, Normal saline
- Keywords
- intraventricular hemorrhage thrombolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlteplaseDrug
Also called Cathflo Activase, rt-PA
1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Normal salineOther
1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
| Study group | Role | What they receive |
|---|---|---|
| Alteplase | Experimental | administration of alteplase via the intraventricular catheter Receives: Drug: Alteplase |
| Saline Placebo | Placebo comparator | 1 ml of normal saline administered via the intraventricular catheter Receives: Other: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 30 days and 180 days
Secondary outcomes (41)
All Cause Mortality
Measured: 180 days
Clot Removal (Amount of Residual Blood)
Change in blood volume measured between stability scan and end of treatment scan
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 180 days
Safety/Mortality - Mortality Within 30 Days
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Measured: 30 days
Safety/Mortality - Bacterial Brain Infections Within 30 Days
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Measured: 30 days
Safety/Mortality - Systematic Bleeds Within 72 Hours
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Measured: 72 hours
Safety/Mortality - Systematic Bleeds Within 30 Days
Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.
Measured: 30 days
Adverse and Serious Adverse Events
Assessment of number of adverse and serious adverse events by treatment group.
Measured: 180 days
Predicting Hazards of Death by Treatment Group
Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2008 (estimated)
- Study startJul 2009
- Primary completionJul 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Intraventricular HemorrhageStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Genentech, Inc., Emissary International LLC
- Responsible party
- Sponsor
- Investigators
- Daniel F. Hanley, MD, Study chair, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00784134
- Sponsor's protocol ID
- IVH06
- Other IDs
- 5U01NS062851-05
- Acronym
- CLEAR III
- Status last verified
- Nov 2018
- First submitted
- 31 Oct 2008
- Last updated
- 5 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 35086362Hansen 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.
PubMed 32026447Porter 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.
PubMed 31571176Eslami 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.
PubMed 31177984Fam 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.
PubMed 28887375Hanley 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.
PubMed 28081952Webb 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.
PubMed 26243227
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
- ClinicalTrials.gov ID
- NCT00784134
- Acronym / sponsor ID
- CLEAR III / IVH06
- Conditions
- Intraventricular Hemorrhage
- Keywords
- intraventricular hemorrhage thrombolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Genentech, Inc., Emissary International LLC
- Study start
- Jul 2009
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 3 Nov 2008 (estimated)
- Results
- Posted 2 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alteplase | Experimental | Drug: Alteplaseadministration of alteplase via the intraventricular catheter |
| Saline Placebo | Placebo comparator | Other: Normal saline1 ml of normal saline administered via the intraventricular catheter |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlteplaseAlso: Cathflo Activase, rt-PA1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses | Drug | Alteplase |
| Normal saline1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses | Other | Saline Placebo |
Primary outcome
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).
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).
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).
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).
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).
41 secondary outcomes
All Cause Mortality
Time frame: 180 days
Clot Removal (Amount of Residual Blood)
Time frame: 72 hours
Intensity of Critical Care Management - Hospital Days
Time frame: 30 days
Intensity of Critical Care Management - ICU Days
Time frame: 30 days
Intensity of Critical Care Management - ICP Management
Time frame: 30 days
Intensity of Critical Care Management - Mechanical Ventilation
Time frame: 30 days
Intensity of Critical Care Management - Pressors
Time frame: 30 days
Intensity of Critical Care Management - Shunts
Time frame: 30 days
Intensity of Critical Care Management - All Infections
Time frame: 30 days
Intensity of Critical Care Management - Pneumonia
Time frame: 30 days
Intensity of Critical Care Management - All Infections
Time frame: 180 days
Safety/Mortality - Mortality Within 30 Days
Time frame: 30 days
Safety/Mortality - Bacterial Brain Infections Within 30 Days
Time frame: 30 days
Safety/Mortality - Systematic Bleeds Within 72 Hours
Time frame: 72 hours
Safety/Mortality - Systematic Bleeds Within 30 Days
Time frame: 30 days
Adverse and Serious Adverse Events
Time frame: 180 days
Predicting Hazards of Death by Treatment Group
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic)
Time frame: 180 days
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic)
Time frame: 180 days
Functional Status - Barthel Index
Time frame: 180 days
Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability
Time frame: 180 days
Functional Status - National Institutes of Health Stroke Scale (NIHSS)
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Strength
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Mobility
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Hand Function
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Communication
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Thinking
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Emotion
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Participation
Time frame: 180 days
Quality of Life - Stroke Impact Scale (SIS) - Recovery
Time frame: 180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35086362Roh 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.
- Derived from this study: PubMed 32026447Hansen 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.
- Derived from this study: PubMed 31571176Porter 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.
- Derived from this study: PubMed 31177984Eslami 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.
- Derived from this study: PubMed 28887375Fam 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.
- Derived from this study: PubMed 28081952Hanley 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.
- Derived from this study: PubMed 26243227Webb 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel F. Hanley, MD study chair
Johns Hopkins University
81 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alteplase and Normal saline in people with Intraventricular Hemorrhage, run by Johns Hopkins University at 81 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 81 sites in United States, Germany, Brazil, Hungary, Israel and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis (time frame: 180 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00784134, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2018.