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

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Katrina Van De Bruinhorst

Principal Investigator
Louis Whitworth, M.D.

Official Title

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

Brief Overview

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).


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.

Participant Eligibility

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

- 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

- 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

- 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

- 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.