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MIS+rtPA for ICH Evacuation (MISTIE)
This study is currently recruiting participants.
Verified by Johns Hopkins University, July 2009
First Received: September 21, 2005   Last Updated: July 21, 2009   History of Changes
Sponsor: Johns Hopkins University
Collaborators: National Institutes of Health (NIH)
Genentech
Information provided by: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00224770
  Purpose

The purpose of this trial is to determine the safety of using a combination of minimally invasive surgery and clot lysis with rt-PA to remove intracerebral hemorrhage (ICH). The procedure is to use image-based surgery (MRI or CT) to provide catheter access to ICH for the intervention, which is a one-time clot aspiration followed by instillation of rt-PA over 72 hours. We propose to test if this intervention facilitates more rapid and complete recovery of function and decreased mortality from this condition compared to conventional medical management without subjecting the patient to craniotomy. The specific objective of this trial is to test the safety of this intervention and assess its ability to remove blood clot from brain tissue.


Condition Intervention Phase
Intracerebral Hemorrhage
Drug: Cathflo Activase (drug)
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study
Official Title: Minimally Invasive Surgery Plus rtPA for Intracerebral Hemorrhage Evacuation

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Procedure related mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Incidence of cerebritis, meningitis [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Rate of rebleeding [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of clot size reduction at Days 4-5 determined by CT scans [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
  • 90- & 180-day GOS, eGOS, Rankin, Stroke Impact Scale [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
  • Post-operative size reduction [ Time Frame: 180-days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 110
Study Start Date: August 2005
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Medical Managment: Active Comparator Drug: Cathflo Activase (drug)
The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3, 1.0, or 3.0 mg of recombinant tissue plasminogen activator, rt-PA, CathFlo®) through the catheter once every eight hours for up to 72 hours with best medical care.
Surgical Management: Active Comparator Drug: Cathflo Activase (drug)
The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3, 1.0, or 3.0 mg of recombinant tissue plasminogen activator, rt-PA, CathFlo®) through the catheter once every eight hours for up to 72 hours with best medical care.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-80
  • GCS < 14 or a NIHSS > or equal to 6
  • Spontaneous supratentorial ICH > or equal to 20cc
  • Symptoms less than 12 hours prior to diagnostic CT scan (an unknown time of symptom onset is exclusionary)
  • Intention to initiate surgery within 48 hours after diagnostic CT
  • First dose can be given within 54 hours after diagnostic CT (delays for post surgical stabilization of catheter bleeding or because of unanticipated surgical delay are acceptable with approved waiver from the coordinating center)
  • Six-hour clot size equal to the most previous clot size + 5 cc (as determined by an additional CT scan at least 6 hours after the initial stability scan (A*B*C)/2 method)
  • SBP < 200 mmHg sustained for 6 hours recorded closest to time of randomization
  • Historical Rankin score of 0 or 1
  • Negative pregnancy test

Exclusion Criteria:

  • Infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy)
  • Patients with platelet count < 100,000, INR > 1.4, or an elevated PT or APTT (reversal of coumadin is permitted but the patient must not require coumadin during the acute hospitalization). Irreversible coagulopathy either due to medical condition or prior to randomization
  • Clotting disorders
  • Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease
  • Patients with a mechanical valve
  • Patients with unstable mass or evolving intracranial compartment syndrome
  • Ruptured aneurysm, AVM, vascular anomaly
  • Greater than 80 years (higher incidence of amyloid)
  • Under 18 years of ag e (high incidence of occult vascular malformation)
  • Pregnant (positive pregnancy test) or lactating females (likelihood of altered coagulation function associated with the high estrogen/progesterone state)
  • Irreversibly impaired brainstem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS less than or equal to 4
  • Historical Rankin score greater than or equal to 2
  • Intraventricular hemorrhage requiring external ventricular drainage
  • Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts
  • Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention
  • Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis
  • In the investigator's opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus MIS+rtPA
  • 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
  • Participation in another simultaneous trial of ICH treatment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00224770

Contacts
Contact: Karen Lane, CCRP 410-614-6996 klane@jhmi.edu

  Hide Study Locations
Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Jennifer Varma, MSN     310-825-4095     jvarma@mednet.ucla.edu    
Principal Investigator: Neil Martin, MD            
Stanford University Recruiting
Palo Alto, California, United States, 94034
Contact: Ryan Snyder     650-736-7648     rsnider@stanford.edu    
Principal Investigator: Christine Wijman, MD            
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94143
Contact: Michele Meeker     415-206-3200     meekerm@neurosurg.ucsf.edu    
Contact: Adam Kincaid     415-206-4457     akincaid@neurosurg.ucsf.edu    
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Shoshana Goldberg     202-784-0757     sg434@georgetown.edu    
Principal Investigator: Chelsea S Kidwell, MD            
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32216
Contact: Alexa Richie     904-953-7839     richie.alexa@mayo.edu    
United States, Illinois
Rush University Recruiting
Chicago, Illinois, United States, 60612
Contact: Susan Dvojack, MS     312-563-2208     Susan_A_Dvojack@rush.edu    
Principal Investigator: Richard Temes, MD, MS            
NorthShore University Health System Recruiting
Evanston, Illinois, United States, 60201
Contact: Jennifer Jaffe     847-570-1675     jjaffe@northshore.org    
Principal Investigator: Issam Awad, MD            
Loyola University Medical Center Recruiting
Maywood, Illinois, United States, 60153
Contact: Linda Chadwick, BSN, RN     708-216-6638     lchadwick@lumc.edu    
Principal Investigator: Michael J Schneck, MD            
United States, Maryland
Johns Hopkins University/Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Shannon LeDroux     410-502-0505     sledrou1@jhmi.edu    
Principal Investigator: Judy Huang, MD            
University of Maryland Medical Systems Recruiting
Baltimore, Maryland, United States, 21201
Contact: Charlene Aldrich, RN     410-328-5332     CALDRICH@smail.umaryland.edu    
Principal Investigator: E. Francois Aldrich, MD            
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Meaghan Whalen     617-726-7544     mbwhalen@partners.org    
Contact: Diedre Buckley     617-726-5531     dbuckley@parners.org    
United States, Michigan
Bronson Medical Hospital Recruiting
Kalamazoo, Michigan, United States, 49007
Contact: Karen Bergman, RN, Phdc     269-341-7587     bergmank@bronsonhg.org    
Principal Investigator: Jeffrey Fletcher, MD            
United States, Missouri
ST. Luke's Hospital Recruiting
Kansas City, Missouri, United States, 64111
Contact: Jennifer McIntire, RN     816-932-7985     jmcintire@saint-lukes.org    
Principal Investigator: Paula Camarata, MD            
United States, New Jersey
New Jersey Medical School Recruiting
Edison, New Jersey, United States, 08818
Contact: Albert Obiozo, MD     732-321-7000 ext 68897     aobiozo@solarishs.org    
Principal Investigator: Kevin Crutchfield, MD            
United States, New York
Mt. Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Sandra Augustine, RN     212-241-1665     sandra.augustine@mountsinai.org    
Principal Investigator: Joshua Bederson, MD            
Columbia University Not yet recruiting
New York, New York, United States, 10027
Contact: Lashana Lewis     212-342-1188     lsl2109@columbia.edu    
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Joanna Stoner     919-668-5275     stone034@bronsonhg.org    
Principal Investigator: Carmelo Graffagnino, MD            
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Carolyn Koenig     513-558-3518     koenigch@ucmail.uc.edu    
Contact: Becky Reinert     513-558-0496     gibsonrk@ucmail.uc.edu    
Principal Investigator: Mario Zuccarello, MD            
Case Western University Not yet recruiting
Cleveland, Ohio, United States, 44106
Contact: Valerie Cwiklinski     216-983-5144     valerie.cwiklinsk@uhhospitals.org    
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Emerson Clement, PhD     215-707-4071     emerson.clement@tuhs.temple.edu    
Principal Investigator: Christopher Loftus            
Thomas Jefferson University Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Deborah August     215-503-1984     deborah.august@jefferson.edu    
University of Pittsburgh Medical Center Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Deborah Crowley     412-647-4992     crowleyda@upmc.edu    
Contact: Sharon DeCesare, CCRC     412-647-8445     decesares@upmc.edu    
Principal Investigator: Larence Wechsler, MD            
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Marc Lapointe     843-792-2993     lapointe@musc.edu    
Principal Investigator: Dilantha Ellegala            
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Karinda Langford, BS     713-798-7518     kjlangofo@bcm.tmc.edu    
Principal Investigator: George Lopez, MD,PhD            
University of Texas HSC, San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Anne Leonard     210-567-5625     leonarda@uthscsa.edu    
Principal Investigator: Jean-Louis Caron, MD            
United States, Virginia
Inova Fairfax Hospital Not yet recruiting
Fairfax, Virginia, United States, 22042
Contact: Janet Rosecan     703-776-4223     janet.rosecan@inova.org    
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Randall Merchant, PhD     804-828-9528     rmerchan@hsc.vcu.edu    
Principal Investigator: William Broaddus, MD            
Canada, Quebec
Montreal Neurological Institute at McGill University Recruiting
Montreal, Quebec, Canada, H3A 2B4
Contact: Nelly Delouya     514-398-5903     nelly.delouya@mcgill.ca    
Principal Investigator: David Sinclair, MD, FRCSC            
Germany
Universitatsklinikum Erlangen Not yet recruiting
Erlangen, Germany
Contact: Juergen Bardutzky         juergen.bardutzky@uk-erlangen.de    
Universitatsmedizin Goettingen Not yet recruiting
Goettingen, Germany
Contact: Rhode Viet         viet.rhode@med.uni-goettingen.de    
University of Heidelberg Not yet recruiting
Heidelberg, Germany, 69117
Contact: Sylvia Treiber         sylvia.treiber@med.uni-heidelberg.de    
United Kingdom
University of Cambridge Not yet recruiting
Cambridge, United Kingdom
Contact: Ming-Yuan Tseng     + 44 1223 33 1763     myt22@cam.ac.uk    
Newcastle General Hospital Not yet recruiting
Newcastle, United Kingdom
Contact: Barbara Gregson, PhD     +44 191 233 6161 ext 22175     barbara.gregson@ncl.ac.uk    
Principal Investigator: David Mendelow, MD            
Sponsors and Collaborators
Johns Hopkins University
Genentech
Investigators
Study Chair: Daniel F. Hanley, MD Johns Hopkins University
Principal Investigator: Mario Zuccarello, MD University of Cincinnati
  More Information

Additional Information:
No publications provided

Responsible Party: Johns Hopkins University ( Daniel F. Hanley, MD )
Study ID Numbers: ICH01, 1 R01 NS046309-01 A1
Study First Received: September 21, 2005
Last Updated: July 21, 2009
ClinicalTrials.gov Identifier: NCT00224770     History of Changes
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cerebral Hemorrhage
Molecular Mechanisms of Pharmacological Action
Hematologic Agents
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents
Cardiovascular Agents
Intracranial Hemorrhages
Hemorrhage
Brain Diseases
Cerebrovascular Disorders
Pharmacologic Actions
Fibrin Modulating Agents
Pathologic Processes
Therapeutic Uses
Cardiovascular Diseases

ClinicalTrials.gov processed this record on November 27, 2009