Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation (MISTIE)

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
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 17, 2015
Last verified: June 2015
  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. All MISTIE intention to treat subjects represent the hypothesized test group. The ICES cohort is to be analyzed separately.


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/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Safety Outcome Number 1: Rate of Mortality [ Time Frame: 30 days from randomization ] [ Designated as safety issue: Yes ]
    Percentage of participants who died during the first 30 days after randomization.

  • Safety Outcome Number 2: Rate of Procedure-related Mortality [ Time Frame: 7 days from randomization ] [ Designated as safety issue: Yes ]
    Percentage of participants who died during the first 7 days after randomization.

  • Safety Outcome Number 3: Rate of Cerebritis, Meningitis, Bacterial Ventriculitis [ Time Frame: 30 days from randomization ] [ Designated as safety issue: Yes ]
    Percentage of participants who had a bacterial brain infection (cerebritis, meningitis, ventriculitis) within 30 days of randomization.

  • Safety Outcome Number 4: Rate of Symptomatic Rebleeding [ Time Frame: 72 hours post last dose ] [ Designated as safety issue: Yes ]
    The difference in the rate of symptomatic rebleeding 72 hours post last dose.

  • Efficacy Outcome Number 1: Dichotomized Modified Rankin Scale (mRS) at Day 180 [ Time Frame: 180 days from randomization ] [ Designated as safety issue: No ]
    Percentage of participants with dichotomized mRS score in 0-3 range. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale ranges from 0-6: (0) no symptoms at all, (1) no significant disability despite symptoms; able to carry out all usual duties and activities, (2) slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, (3) moderate disability; requiring some help, but able to walk without assistance, (4) moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, (5) severe disability; bedridden, incontinent and requiring constant nursing care and attention, (6) dead


Secondary Outcome Measures:
  • Ordinal Modified Rankin Scale (mRS) at Day 180 [ Time Frame: 180 days from randomization ] [ Designated as safety issue: No ]
    Ordinal distribution of the Modified Rankin Scale score at 180 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale ranges from 0-6: (0) no symptoms at all, (1) no significant disability despite symptoms; able to carry out all usual duties and activities, (2) slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, (3) moderate disability; requiring some help, but able to walk without assistance, (4) moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, (5) severe disability; bedridden, incontinent and requiring constant nursing care and attention, (6) dead.

  • Ordinal Modified Rankin Scale (mRS) at Day 365 [ Time Frame: 365 days from randomization ] [ Designated as safety issue: No ]
    Ordinal distribution of the Modified Rankin Scale score at 365 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale ranges from 0-6: (0) no symptoms at all, (1) no significant disability despite symptoms; able to carry out all usual duties and activities, (2) slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, (3) moderate disability; requiring some help, but able to walk without assistance, (4) moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, (5) severe disability; bedridden, incontinent and requiring constant nursing care and attention, (6) dead.

  • Clot Size Reduction by End of Treatment [ Time Frame: Time from randomization until end of treatment, up to 10 days ] [ Designated as safety issue: No ]
    The percentage of blood clot resolved by the end of treatment CT scan compared to the stability CT scan.

  • Post-operative Clot Size Reduction [ Time Frame: Time from post-operation until end of treatment, up to 10 days ] [ Designated as safety issue: No ]
    The percentage of blood clot resolved by the end of treatment CT scan compared to the post-operative CT scan for surgical patients.


Enrollment: 141
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 Management
Standard of care medical management as per American Heart Association (AHA) guidelines.
Active Comparator: MISTIE Surgical Management

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

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 or 1.0mg of rt-PA, CathFlo®) through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Drug: MIS+Cathflo Activase (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 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.
Other Name: rtPA
Active Comparator: ICES Surgical Management

Intraoperative stereotactic CT-Guided Endoscopic Surgery

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Procedure: Intraoperative stereotactic CT-Guided Endoscopic Surgery
Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative targeting arm as MISTIE arm. No rt-PA administered, and in addition to best medical care.

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. This tests the first step of the MISTIE surgical procedure with an endoscope, not a rigid cannula.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00224770

  Show 29 Study Locations
Sponsors and Collaborators
Daniel Hanley
Genentech, Inc.
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
Results First Received: September 21, 2014
Last Updated: June 17, 2015
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 27, 2015