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

Condition(s) targeted: Intracerebral Hemorrhage

Intervention: Cathflo Activase (drug) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Johns Hopkins University

Official(s) and/or principal investigator(s):
Daniel F. Hanley, MD, Study Chair, Affiliation: Johns Hopkins University
Mario Zuccarello, MD, Principal Investigator, Affiliation: University of Cincinnati

Overall contact:
Nichol McBee, MPH, CCRP, Phone: 410-614-6996, Email: nmcbee@jhmi.edu

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.

Official title: Minimally Invasive Surgery Plus rtPA for Intracerebral Hemorrhage Evacuation (MISTIE)

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study

Primary outcome:

30-day mortality

Procedure related mortality

Incidence of cerebritis, meningitis

Rate of rebleeding

Secondary outcome:

Rate of clot size reduction at Days 4-5 determined by CT scans

90 & 180 day GOS, Rankin, Stroke Impact Scale

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 18-80

- GCS < 14 or a NIHSS > 6

- Spontaneous supratentorial ICH > 25cc

- Symptoms less than 12 hours prior to diagnostic CT scan (an unknown time of symptom

onset is exclusionary)

- First dose can be given within 36 hours of symptom onset (plus a 2-hour feasibility

window with approval from the coordinating center, reserved for only those situations where the patient is eligible, consented, stable but personnel scheduling prohibits giving the first dose within the 36-hour window)

- 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

- 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. 7, PT > 15s, or an elevated 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.

Nichol McBee, MPH, CCRP, Phone: 410-614-6996, Email: nmcbee@jhmi.edu

Evanston Northwestern Healthcare, Evanston, Illinois 60201, United States; Recruiting
Judith O'Leary, RN, Phone: 847-570-1632, Email: JOLeary@enh.org
Issam Awad, MD, Principal Investigator

Johns Hopkins University, Baltimore, Maryland 21287, United States; Recruiting
Shannon Le Droux, Phone: 410-502-0505, Email: sledrou1@jhmi.edu
Rafael Tamargo, MD, Principal Investigator
Richard Clatterbuck, MD, Principal Investigator
Judy Huang, MD, Sub-Investigator
Neal Naff, MD, Sub-Investigator

University of Maryland Medical Systems, Baltimore, Maryland, United States; Recruiting
Charlene Aldrich, RN, Phone: 410-328-5332, Email: CALDRICH@smail.umaryland.edu
Francois Aldrich, MD, Principal Investigator

Wayne State University, Detroit, Michigan 48201, United States; Recruiting
Flicia Mada, RN, Phone: 313-745-1893, Email: fmada@med.wayne.edu
William Coplin, MD, Principal Investigator
Robert Johnson, MD, Principal Investigator

Washington University, St. Louis, Missouri 63110, United States; Recruiting
Brenda Hall, Phone: 314-362-3559
Greg Zipfel, MD, Principal Investigator

Mt. Sinai Medical Center, New York, New York 10029, United States; Recruiting
Fatima Sehba, PhD, Phone: 212-241-6504, Email: fatima.sehba@mssm.edu
Joshua Bederson, MD, Principal Investigator

University of Cincinnati, Cincinnati, Ohio 45267, United States; Recruiting
Suzanne Kempisty-Cliver, RN, Phone: 513-558-3590, Email: kempiss@ucmail.uc.edu
Mario Zuccarello, MD, Principal Investigator

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Bonnie Muntz-Pope, RN, Phone: 843-792-8967, Email: muntzpob@musc.edu
Byron Bailey, MD, Principal Investigator
Marc Lapointe, PharmD, Sub-Investigator

Virginia Commonwealth University, Richmond, Virginia 23298, United States; Recruiting
Randall Merchant, PhD, Phone: 804-828-9528, Email: rmerchan@hsc.vcu.edu
William Broaddus, MD, Principal Investigator

Starting date: August 2005
Last updated: April 1, 2008