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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01827046




Registration number
NCT01827046
Ethics application status
Date submitted
1/04/2013
Date registered
9/04/2013
Date last updated
27/09/2019

Titles & IDs
Public title
Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III
Scientific title
Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III
Secondary ID [1] 0 0
U01NS080824
Secondary ID [2] 0 0
NA_00080619
Universal Trial Number (UTN)
Trial acronym
MISTIE-III
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intracerebral Hemorrhage 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - rt-PA

Experimental: MIS plus rt-PA management - Subjects randomized to the Minimally Invasive Surgery (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.

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.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dichotomized, Adjudicated Modified Rankin Scale Score 0-3 vs. 4-6 at 365 Days Post Ictus (Adjusted)
Timepoint [1] 0 0
Day 365
Secondary outcome [1] 0 0
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 365 Days Post Ictus (Adjusted)
Timepoint [1] 0 0
Day 365
Secondary outcome [2] 0 0
All Cause Mortality Longitudinally From Ictus to 365 Days (Adjusted)
Timepoint [2] 0 0
Day 365
Secondary outcome [3] 0 0
Clot Removal (Amount of Residual Blood)
Timepoint [3] 0 0
24 hours after last dose
Secondary outcome [4] 0 0
Patient Disposition: Home Days Over 365 Days Time From Ictus.
Timepoint [4] 0 0
During 365 days of follow-up
Secondary outcome [5] 0 0
Patient Disposition: Patient Location at 365 Days Post Ictus (i.e., Good vs. Bad Location) (Adjusted)
Timepoint [5] 0 0
Day 365
Secondary outcome [6] 0 0
Dichotomized, Adjudicated, Cross-sectional Modified Rankin Scale (mRS) Score 0-3 vs. 4-6 180 Days Post Ictus (Adjusted)
Timepoint [6] 0 0
Day 180
Secondary outcome [7] 0 0
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 180 Days Post Ictus (Adjusted)
Timepoint [7] 0 0
Day 180
Secondary outcome [8] 0 0
Type and Intensity of ICU Management: ICU Days
Timepoint [8] 0 0
Up to 365 days
Secondary outcome [9] 0 0
Type and Intensity of ICU Management: Hospital Days
Timepoint [9] 0 0
Up to 365 days
Secondary outcome [10] 0 0
EQ-VAS
Timepoint [10] 0 0
Day 365
Secondary outcome [11] 0 0
EuroQol 5 Dimensional Scale (EQ-5D)
Timepoint [11] 0 0
Day 365

Eligibility
Key inclusion criteria
* Spontaneous supratentorial ICH = 30 mL diagnosed using radiographic imaging (computerized tomography (CT), computerized tomography angiography (CTA), etc.), with a Glasgow Coma Scale (GCS) = 14 or a NIHSS = 6.
* Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth < 5 mL as measured by ABC/2 method).
* Symptoms less than 24 hours prior to diagnostic CT (dCT) scan (an unknown time of onset is exclusionary).
* Ability to randomize between 12 and 72 hours after dCT.
* Systolic Blood Pressure (SBP) < 180 mmHg sustained for six hours recorded closest to the time of randomization.
* Historical Rankin score of 0 or 1.
* Age = 18 and older.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Infratentorial hemorrhage.
* Intraventricular hemorrhage (IVH) requiring treatment for IVH-related (casting) mass effect or shift due to trapped ventricle. External ventricular drain (EVD) to treat intracranial pressure (ICP) is allowed.
* 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, hemorrhagic conversion of an ischemic infarct, recurrence of a recent (< 1 year) hemorrhage diagnosed with radiographic imaging.
* Patients with unstable mass or evolving intracranial compartment syndrome.
* Platelet count < 100,000; international normalized ratio (INR) > 1.4.
* 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, Fresh Frozen Plasma (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, Apixaban, and/or Rivaroxaban (or a similar medication from the similar medication class) 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.
* 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.
* Not expected to survive to the day 365 visit due to co-morbidities and/or are do not resuscitate (DNR)/ do not intubate (DNI) status prior to randomization.
* 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. Presence of bio-prosthetic valve(s) is permitted.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2018
Sample size
Target
Accrual to date
Final
499
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - North Adelaide
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2015 - Camperdown
Recruitment postcode(s) [2] 0 0
5006 - North Adelaide
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment outside Australia
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Alabama
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Arizona
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California
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Connecticut
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Kansas
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Kentucky
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Maine
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Michigan
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Wisconsin
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Ontario
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Quebec
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China
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Guangdong
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China
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Beijing
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China
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Chongqing
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Germany
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Bonn
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Germany
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Heidelberg
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Germany
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Mainz
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Germany
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Munich
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Hungary
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Baranya County
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Debrecen
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Hungary
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Szeged
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Israel
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Ramat-Gan
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Israel
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Petach Tikva
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Spain
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Biscay
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Spain
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Barcelona
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Valladolid
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United Kingdom
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Manchester
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Glasgow
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Newcastle upon Tyne
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United Kingdom
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Southampton

Funding & Sponsors
Primary sponsor type
Other
Name
Johns Hopkins University
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Genentech, Inc.
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Emissary International LLC
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Daniel F. Hanley, MD
Address 0 0
Johns Hopkins University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01827046