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Trial record 1 of 350 for:    CLEAR III
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Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III)

This study has been completed.
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Emissary International LLC
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University Identifier:
First received: October 31, 2008
Last updated: April 12, 2016
Last verified: April 2016
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 Intervention Phase
Intraventricular Hemorrhage Drug: Cathflo Activase Other: Normal saline Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Resource links provided by NLM:

Further study details as provided by Daniel Hanley, Johns Hopkins University:

Primary Outcome Measures:
  • Modified Rankin Scale (Dichotomized 0-3) [ Time Frame: 180 days ]
    Analysis modified on September 29, 2015 to account for adaptive randomization.

  • Modified Rankin Scale (Ordinal Scale) [ Time Frame: 180 days ]
  • Modified Rankin Scale (Dichotomized 0-4) [ Time Frame: 180 days ]
  • Random effects assessment of site effect (modified Rankin Scale 0-3) [ Time Frame: 180 days ]
  • Modified Rankin Scale (Longitudinal 0-3) [ Time Frame: 180 days ]

Secondary Outcome Measures:
  • All cause mortality [ Time Frame: 180 days ]
  • Clot removal (Amount of residual blood) [ Time Frame: 72 h ]
  • Intensity of critical care management [ Time Frame: 30 days ]
    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.

  • Safety/Mortality [ Time Frame: 30 days ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality within 30 days.

  • Adverse and Serious Adverse Events [ Time Frame: 180 days ]
  • Predictors of Mortality using Cox Proportional Hazards Model [ Time Frame: 180 days ]
  • Sub-Group Analyses [ Time Frame: 180 days ]
    Assessment of mRS score 0-3 compared by race, gender, age, IVH size, and ICH location.

  • Functional Status [ Time Frame: 180 days ]
    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group.

  • Quality of Life [ Time Frame: 180 days ]
    Assessment of SIS and EuroQol Visual Analog Scale by group.

Enrollment: 500
Study Start Date: July 2009
Study Completion Date: January 2016
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rt-PA
administration of rt-PA via the intraventricular catheter
Drug: Cathflo Activase
1.0 mg of Cathflo Activase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Other Name: 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


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

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
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Please refer to this study by its identifier: NCT00784134

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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
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Palo Alto, California, United States, 94034
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Hartford Hospital
Hartford, Connecticut, United States, 06106
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New Haven, Connecticut, United States, 06520-8018
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Washington DC, District of Columbia, United States, 20007
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Mayo Clinic, Jacksonville
Jacksonville, Florida, United States, 32224
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Sarasota, Florida, United States, 34232
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Chicago, Illinois, United States, 60612
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Ruan Neurology Clinical and Research Center
Des Moines, Iowa, United States, 50314
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Iowa City, Iowa, United States, 52242
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Kansas City, Kansas, United States, 66160
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Detroit, Michigan, United States, 48202
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Kansas City, Missouri, United States, 64111
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Springfield, Missouri, United States, 65804
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St. Louis, Missouri, United States, 63104
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Cooper University Hospital
Camden, New Jersey, United States, 08103
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Edison, New Jersey, United States, 08818
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Buffalo, New York, United States, 14203
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Manhasset, New York, United States, 11030
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Winston-Salem, North Carolina, United States, 27157
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Cincinnati, Ohio, United States, 45219
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Cleveland, Ohio, United States, 44106
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Portland, Oregon, United States, 04102
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Portland, Oregon, United States, 97225
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Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
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Hershey, Pennsylvania, United States, 17033
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Philadelphia, Pennsylvania, United States, 19107
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Philadelphia, Pennsylvania, United States, 19140
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Philadelphia, Pennsylvania, United States, 19141
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Pittsburgh, Pennsylvania, United States, 15212
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Pittsburgh, Pennsylvania, United States, 15213
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Medical University of South Carolina
Charleston, South Carolina, United States, 29425
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Nashville, Tennessee, United States, 37232
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University of Texas, Southwestern, Dallas
Dallas, Texas, United States, 75390
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Richmond, Virginia, United States, 23298
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Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
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
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University of Alberta
Edmonton, Alberta, Canada, T6G 2B7
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Montreal Neurological Institute at McGill University
Montreal, Quebec, Canada, H3A 2B4
University of Erlangen
Erlangen, Germany, 91054
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Halle, Germany, D-06120
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Heidelberg, Germany, 69120
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Leipzig, Germany, 04103
University of Mainz
Mainz, Germany, D-55131
University of Tubingen
Tübingen, Germany, 72076
University of Szeged
Szeged, Csongrad, Hungary, 6725
Honved Korhaz
Budapest, Hungary, 1134
University of Debrecen
Debrecen, Hungary, 4032
University of Pecs
Pecs, Hungary, 7623
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
Bellvitge Hospital
Barcelona, Spain, 08015
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
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
Daniel Hanley
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Emissary International LLC
Study Chair: Daniel F. Hanley, MD Johns Hopkins University
  More Information

Additional Information:
Study Data/Documents: Data repository-VISTA  This link exits the site
Identifier: Data repository-VISTA
when available
Study Protocol  This link exits the site
when available
Statistical Analysis Plan  This link exits the site
when available

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Daniel Hanley, MD, Johns Hopkins University Identifier: NCT00784134     History of Changes
Other Study ID Numbers: IVH06
Study First Received: October 31, 2008
Last Updated: April 12, 2016

Keywords provided by Daniel Hanley, Johns Hopkins University:
intraventricular hemorrhage thrombolysis

Additional relevant MeSH terms:
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
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 processed this record on June 23, 2017