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
- Spontaneous supratentorial intracerebral haemorrhageMedDRA version: 19.1Level: PTClassification code 10062025Term: Intracerebral haematoma evacuationSystem Organ Class: 10042613 - Surgical and medical proceduresTherapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]
- Registration Number
- EUCTR2013-002818-12-DE
- Lead Sponsor
- The John Hopkins University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 499
4.1.1 Spontaneous supratentorial ICH = 30 mL measured by the site utilizing ABC/2 method using radiographic imaging (CT, CTA, etc.), with a GCS = 14 or a NIHSS = 6.
4.1.2 Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth < 5 mL as measured by ABC/2 method). If the clot volume measured on this stability CT scan increases by 5 mL or more, a second stability determination is allowed by repeat CT scan at least 12 hours later. Additional scans are permitted as needed every 12 hours to continue to monitor for stability up until the eligibility time window closes. Subsequent
clot retraction remains inclusionary as long as the ICH clot size remains = 25 mL.
4.1.3 Symptoms less than 24 hours prior to diagnostic CT (dCT) scan. An unknown time of onset is exclusionary. Use the time the patient was last known to be well for patients that awaken from sleep with symptoms.
4.1.4 Ability to randomize between 12 and 72 hours after dCT.
4.1.5 SBP < 180 mmHg sustained for six hours recorded closest to the time of randomization.
4.1.6 Historical Rankin score of 0 or 1.
4.1.7 Age = 18 and older.
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
4.2.1 Infratentorial hemorrhage.
4.2.2 Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, hemorrhagic conversion of an ischemic infarct, recurrence of a recent (< 1 year) hemorrhage, diagnosed with radiographic imaging.
4.2.3 Patients with unstable mass or evolving intracranial compartment syndrome.
4.2.4 Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS = 4. 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.
4.2.6 Intraventricular hemorrhage requiring treatment for IVH-related (casting) mass effect or shift due to trapped ventricle. EVD to treat ICP is allowed.
4.2.7 Platelet count < 100,000; INR > 1.4.
4.2.8 Any irreversible coagulopathy or known clotting disorder.
4.2.9 Inability to sustain INR = 1.4 using short- and long-acting procoagulants (such as but not limited to NovoSeven, FFP, and/or vitamin K).
4.2.10 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.
4.2.11 Use of Dabigatran, Apixaban, and/or Rivaroxaban (or a similar medication from the similar medication class) prior to symptom onset.
4.2.12 Internal bleeding involving retroperitoneal, gastrointestinal, or genitourinary site or respiratory tract bleeding.
4.2.13 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.
4.2.14 Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
4.2.15 Allergy/sensitivity to rt-PA.
4.2.16 Prior enrollment in the study.
4.2.17 Participation in a concurrent interventional medical investigation or clinical trial.
Patients in observational, natural history, and/or epidemiological studies not involving an intervention are eligible.
4.2.18 Not expected to survive to the day 365 visit due to co-morbidities, or are DNR/DNI status prior to randomization.
4.2.19 Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease.
4.2.20 Patients with a mechanical heart valve. Presence of bio-prosthetic valve(s) is permitted.
4.2.21 Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial
endocarditis. Atrial fibrillation without mitral stenosis is permitted.
4.2.22 Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
4.2.23 Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
4.2.24 In the investigator’s opinion, the patient is unstable and would benefit from a specific inter
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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. <br>;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
- Secondary Outcome Measures
Name Time Method 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;Timepoint(s) of evaluation of this end point: 30, 180 and 365 days.