MISTIE III. 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.
- Conditions
- Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]MedDRA version: 17.1 Level: PT Classification code 10062025 Term: Intracerebral haematoma evacuation System Organ Class: 10042613 - Surgical and medical proceduresSpontaneous supratentorial intracerebral haemorrhage
- Registration Number
- EUCTR2013-002818-12-ES
- Lead Sponsor
- The John Hopkins University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 499
1)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.
2)Symptoms less than 24 hours prior to diagnostic CT (dCT) scan (an unknown time of onset is exclusionary).
3)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).
4)SBP < 180 mmHg sustained for six hours recorded closest to the time of randomization.
5)Historical Rankin score of 0 or 1.
6)Age ? 18 and ? 80.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 250
1)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.
2)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 anticoagulation 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.
3)Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
4)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.
5)Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
6)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.
7)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.
8)Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: To show whether the reduction in the size of the blood clot in the brain acheived by using MIS+rt-PA is related to improved functional outcome, as compared to medically treated subjects.;Primary end point(s): Overall better functional outcome at 180 days, as defined by the modified Rankin Scale (mRS) using dichotomized adjudicated mRS 0-3 vs. 4-6 at 180 days post-stroke;Timepoint(s) of evaluation of this end point: 180 days post-stroke;Main Objective: To show whether minimally invasive surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) for three days improves outcome at six months as compared to standard medical treatment in patients with spontaneous bleeding in the brain (with no underlying cause)(ICH). It will also show whether 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
Name Time Method <br> Secondary end point(s): Dichotomized adjudicated mRS at 365 days post-stroke 0-3 vs. 4-6 and 0-2 vs. 3-6<br> Ordinal adjudicated mRS (0 ? 6) at 180 days post-stroke<br> Mortality and Safety Events at 30 days post-randomization including procedurerelated<br> mortality, symptomatic bleeding rate, and infection rate<br> Mortality at 180 days post stroke<br> Functional Status: NIHSS, Barthel, GOS, GOSE, MMSE at 180 days<br> Type and intensity of ICU management: ICU days, hospital days, patient disposition at 180 days and 365 days<br> Quality of life: SIS, EQ-5D, PBSI,Personal Health Utility Assessment<br> Cost<br> ;Timepoint(s) of evaluation of this end point: 30, 180 and 365 days.