MIS+rtPA for ICH Evacuation (MISTIE)

This study has been completed.
Sponsor:
Collaborators:
Genentech
Emissary International LLC
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00224770
First received: September 21, 2005
Last updated: June 5, 2013
Last verified: June 2013
  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 ICES arm of the trial will determine the safety of endoscopic surgery to remove ICH.


Condition Intervention Phase
Intracerebral Hemorrhage
Drug: MIS+Cathflo Activase (drug)
Procedure: Intraoperative stereotactic CT-Guided Endoscopic Surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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: 7 days ] [ Designated as safety issue: No ]
  • 90-, 180-, & 365-day GOS, eGOS, Rankin, Stroke Impact Scale [ Time Frame: 365 days ] [ Designated as safety issue: No ]
  • Post-operative size reduction [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Enrollment: 143
Study Start Date: August 2005
Study Completion Date: April 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Medical Managment
Active Comparator: MISTIE Surgical Management
Minimally invasive surgery with clot lysis with rt-PA.
Drug: MIS+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.
Other Name: rtPA
Active Comparator: ICES Surgical Management
Endoscopic removal of ICH
Procedure: Intraoperative stereotactic CT-Guided Endoscopic Surgery

Detailed Description:

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.

The Intraoperative stereotactic CT-guided Endoscopic Surgery (ICES) arm of the trial will determine the safety, feasibility and effectiveness of endoscopic surgery to remove ICH.

We propose to test if these interventions facilitate 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 these interventions and assess their ability to remove blood clot from brain tissue.

  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) (Does not apply to ICES Tier)
  • 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 (Does not apply to ICES Tier)
  • Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention (Does not apply to ICES Tier)
  • Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis (Does not apply to ICES Tier)
  • 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

  Show 29 Study Locations
Sponsors and Collaborators
Daniel Hanley
Genentech
Emissary International LLC
Investigators
Study Chair: Daniel F. Hanley, MD Johns Hopkins University
Principal Investigator: Mario Zuccarello, MD University of Cincinnati
Principal Investigator: Paul Vespa, MD University of California, Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Daniel Hanley, MD, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00224770     History of Changes
Other Study ID Numbers: ICH01, R01NS046309
Study First Received: September 21, 2005
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hemorrhage
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
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on April 17, 2014