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Trial record 2 of 2 for:    MISTIE

Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III (MISTIE III)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Johns Hopkins University
Sponsor:
Collaborators:
Genentech, Inc.
Emissary International LLC
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01827046
First received: April 1, 2013
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

A phase III, randomized, case-controlled, open-label, 500-subject clinical trial of minimally invasive surgery plus rt-PA in the treatment of intracerebral hemorrhage (ICH).


Condition Intervention Phase
Intracerebral Hemorrhage
Drug: rt-PA
Phase 3

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 Plus Rt-PA for ICH Evacuation Phase III

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • modified Rankin Scale score [ Time Frame: day 180 ] [ Designated as safety issue: No ]
    Efficacy: Demonstrate that minimally invasive surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) for three days improves functional outcome by a 12% increase in the modified Rankin Scale (mRS) score 0-3 compared to medically treated subjects assessed at 180 days.

  • Rate of mortality, rebleeding, and infection as a measure of safety [ Time Frame: day 30 ] [ Designated as safety issue: Yes ]
    Safety: Demonstrate that early use of MIS+rt-PA for three days is safe for the treatment of ICH relative to rates of mortality, rebleeding, and infection in the medically treated subject at 30 days.


Secondary Outcome Measures:
  • ICH reduction [ Time Frame: day 7 ] [ Designated as safety issue: No ]
    Secondary Objective: Demonstrate that the end of treatment volume and percent of ICH reduction from MIS+rt-PA is related to improved functional outcome, as compared to medically treated subjects.


Estimated Enrollment: 500
Study Start Date: December 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MIS plus rt-PA management
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
Drug: rt-PA
Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
Other Names:
  • Activase
  • Alteplase
  • CathFlo
No Intervention: Medical management
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.

Detailed Description:

Primary Objectives:

Efficacy: Demonstrate that minimally invasive surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) for three days improves functional outcome by a 12% increase in the modified Rankin Scale (mRS) score 0-3 compared to medically treated subjects assessed at 180 days.

Safety: Demonstrate that early use of MIS+rt-PA for three days is safe for the treatment of ICH relative to rates of mortality, rebleeding, and infection in the medically treated subject at 30 days.

Secondary Objective: Demonstrate that the end of treatment volume and percent of ICH reduction from MIS+rt-PA is related to improved functional outcome, as compared to medically treated subjects.

  Eligibility

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

Inclusion Criteria:

  • Spontaneous supratentorial ICH ≥ 30 mL diagnosed using radiographic imaging (CT, CTA, etc.), with a GCS ≤ 14 or a NIHSS ≥ 6.
  • Six-hour clot size equal to the most previous clot size (within 5 mL) as determined by additional CT scans at least 6 hours apart using the ABC/2 method.
  • Symptoms less than 24 hours prior to diagnostic CT (dCT) scan (an unknown time of onset is exclusionary).
  • Intention to initiate surgery between 12 and 72 hours after dCT. First dose can be given within 76 hours after dCT (delays for post surgical stabilization of catheter bleeding or because of unanticipated surgical delay are acceptable with approved waiver from the CCC).
  • SBP < 180 mmHg sustained for six hours recorded closest to the time of randomization.
  • Historical Rankin score of 0 or 1.
  • Age ≥ 18 and ≤ 80.

Exclusion Criteria:

  • Infratentorial hemorrhage.
  • Intraventricular hemorrhage requiring treatment with extraventricular drainage (obstruction of third and fourth ventricles).
  • Thalamic bleeds with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions. Note: Patients with a posterior fossa ICH or cerebellar hematomas are ineligible.
  • Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4.
  • Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease diagnosed with radiographic imaging.
  • Patients with unstable mass or evolving intracranial compartment syndrome.
  • Platelet count < 100,000, INR > 1.4, or an elevated prothrombin time (PT) or activated partial thromboplastin time (aPTT).
  • Any irreversible coagulopathy or known clotting disorder.
  • Inability to sustain INR ≤ 1.4 using short- and long-active procoagulants (such as but not limited to NovoSeven, FFP, and/or vitamin K).
  • Subjects requiring long-term anti-coagulation are excluded. Reversal of anti-coagulation is permitted for medically stable patients who can realistically tolerate the short term risk of reversal. Patient must not require Coumadin (anticoagulation) during the first 30 days, and normalized coagulation parameters must be demonstrated, monitored closely and maintained during the period of brain instrumentation.
  • Use of Dabigatran prior to symptom onset.
  • 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, etc.) or site of recent surgical intervention.
  • Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
  • Allergy/sensitivity to rt-PA.
  • Prior enrollment in the study.
  • Planned or simultaneous participation (between screening and Day-30) in another interventional medical investigation or clinical trial. Patients in observational, natural history, and/or epidemiological studies not involving an intervention are eligible.
  • Subjects who are not expected to survive to the day 365 visit due to co-morbidities and/or are DNR/DNI status prior to randomization are excluded.
  • 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 heart valve.
  • Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis.
  • Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • In the investigator's opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus MIS+rt-PA removal of the ICH.
  • Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
  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: NCT01827046

Contacts
Contact: Amanda Bistran-Hall 4109552536 abistran1@jhmi.edu
Contact: Karen Lane, CMA 4106143461 klane@jhmi.edu

  Show 77 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: Issam Awad, MD University of Chicago
  More Information

No publications provided

Responsible Party: Daniel Hanley, MD, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01827046     History of Changes
Other Study ID Numbers: ICH02
Study First Received: April 1, 2013
Last Updated: August 18, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
intracerebral hemorrhage
ICH
brain hemorrhage
minimally invasive surgery
rt-PA

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 November 23, 2014