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A randomized controlled trial of ultra-early, minimally invasive, hematoma evacuation versus standard care within 8 hours of intracerebral hemorrhage. Patients presenting to the emergency department with stroke due to supratentorial, spontaneous intracerebral hemorrhage >20mL volume will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomized 50:50 using central computerized allocation to minimally invasive hematoma evacuation using the Aurora surgiscope and evacuator (Integra Lifesciences) versus standard medical therapy. The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design with seamless phase 2b-3 transition if the intermediate endpoint (successful hematoma evacuation) is met in analysis of the first 52 patients. Adaptive sample size re-estimation (Mehta and Pocock) will be performed when 160 patients have completed 6 month follow-up (minimum sample size 240, maximum sample size 434).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minimally invasive hematoma evacuation | Experimental | Patients randomized to minimally invasive hematoma evacuation will have neurosurgery followed by standard medical therapy in a stroke care unit or intensive care unit, as appropriate to the patients clinical condition. |
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| Standard care (medical therapy) | No Intervention | Patients randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage in a stroke care unit or intensive care unit, as appropriate to the patients clinical condition, with no planned surgical intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minimally invasive hematoma evacuation | Procedure | Neurosurgery performed via burr hole or minicraniotomy and using the Aurora surgiscope and evacuator (Integra Lifesciences) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dichotomized Modified Rankin Scale Score 0-3 vs. 4-6 at 6 months post-onset (Adjusted) | Modified Rankin Scale (mRS) 0-3 at 6 months, adjusted for age, baseline GCS, immediate pre-treatment ICH volume and immediate pre-treatment IVH volume. | 6 months post-stroke |
| Measure | Description | Time Frame |
|---|---|---|
| Dichotomized Modified Rankin Scale Score 0-2 or no change from baseline vs. 3-6 at 6 months post-onset (adjusted) | Modified Rankin Scale (mRS) 0-2 or no change from baseline at 6 months, adjusted for age, baseline GCS, immediate pre-treatment ICH volume and immediate pre-treatment IVH volume | 6 months post-stroke |
| Measure | Description | Time Frame |
|---|---|---|
| Safety: Death due to any cause at 6 months (adjusted) | Death due to any cause at 6 months, adjusted for age, baseline GCS, immediate pre-treatment ICH volume and immediate pre-treatment IVH volume. | 6 months post-stroke |
| Safety: Hematoma growth or reaccumulation at 24 hours |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Melbourne Brain Centre at the Royal Melbourne Hospital | Contact | +61 3 9342 4424 | info@thembc.org.au |
| Name | Affiliation | Role |
|---|---|---|
| Timothy Kleinig | Royal Adelaide Hospital/University of Adelaide | Principal Investigator |
| Amal Abou-Hamden | Royal Adelaide Hospital/University of Adelaide | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| John Hunter Hospital | Recruiting | Newcastle | New South Wales | 2305 | Australia |
Anonymized individual patient data will be uploaded to the Virtual Stroke Trials Archive (http://www.virtualtrialsarchives.org/vista/) 2 years after the publication of the primary manuscript. Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA-ICH steering committee.
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2 years after the publication of the primary manuscript
Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA-ICH steering committee.
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Patients will receive either minimally invasive hematoma evacuation or standard medical therapy
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The primary outcome of Modified Rankin scale (mRS) and secondary outcomes including National Institutes of Health Stroke Scale (NIHSS) are assessed by a blinded clinician.
| Ordinal analysis of Modified Rankin Scale Score at 6 months post-onset (adjusted) |
Ordinal analysis of Modified Rankin Scale Score (merging mRS 5-6) at 6 months, adjusted for age, baseline GCS, immediate pre-treatment ICH volume and immediate pre-treatment IVH volume |
| 6 months post-stroke |
| Utility-weighted analysis of Modified Rankin Scale Score at 6 months post-onset (adjusted) | Utility-weighted analysis of Modified Rankin Scale Score at 6 months, adjusted for age, baseline GCS, immediate pre-treatment ICH volume and immediate pre-treatment IVH volume | 6 months post-stroke |
| Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted) | Reduction in hematoma volume at 24 hours >70% or <15mL residual volume, adjusted for immediate pre-treatment ICH volume | 24 hours post-randomization |
| Proportion of patients with early neurological improvement at 7 days (adjusted) | Proportion of patients with ≥8 point reduction in National Institutes of Health Stroke Scale (NIHSS) score or reaching 0-1 at 7 days (or at discharge if earlier) adjusted for baseline NIHSS and age | 7 days post-stroke |
Hematoma growth or reaccumulation defined as >33% or >6mL increased volume between baseline and 24 hour scans (or in the intervention arm a hematoma volume on the follow-up scan exceeding the immediate pre-treatment volume), adjusted for the pre-treatment ICH volume. |
| 24 hours post-randomization |
| Intermediate outcome measure (primary outcome measure for Phase 2b component): Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted) | Intermediate outcome measure (primary outcome measure for the Phase 2b component to be analysed for the first 52 patients): Reduction in hematoma volume at 24 hours >70% or <15mL residual volume, adjusted for immediate pre-treatment ICH volume | 24 hours post-randomization |
| Patient Reported Outcomes Measurement Information System (PROMIS10) | 6 and 12 months post-stroke |
| Modified Rankin Scale (mRS) 0-2, 0-3, ordinal and utility-weighted analysis at 12 months | 12 months post-stroke |
| Assessment of Quality of Life (EQ5D) at 12 months | Assessment of Quality of Life (EQ5D) at 12 months (mapped to mRS at baseline) | 12 months post-stroke |
| Length of stay in intensive care unit, acute hospital, acute hospital and rehabilitation | 6 months post-stroke |
| Home time - time spent at home in the first 6 months | 6 months post-stroke |
| John Laidlaw |
| Royal Melbourne Hospital/University of Melbourne |
| Principal Investigator |
| J Mocco | Icahn School of Medicine, Mt Sinai Hospital, New York | Principal Investigator |
| Christopher Kellner | Icahn School of Medicine, Mt Sinai Hospital, New York | Principal Investigator |
| Stephen Davis | Royal Melbourne Hospital/University of Melbourne | Principal Investigator |
| Bruce Campbell | Royal Melbourne Hospital/University of Melbourne | Principal Investigator |
| Prince of Wales Hospital | Not yet recruiting | Sydney | New South Wales | 2031 | Australia |
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| Royal Prince Alfred Hospital | Not yet recruiting | Sydney | New South Wales | 2050 | Australia |
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| Westmead Hospital | Not yet recruiting | Sydney | New South Wales | 2145 | Australia |
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| Liverpool Hospital | Recruiting | Sydney | New South Wales | 2170 | Australia |
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| The Royal Brisbane and Women's Hospital | Recruiting | Brisbane | Queensland | 4029 | Australia |
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| Princess Alexandra Hospital | Not yet recruiting | Brisbane | Queensland | 4102 | Australia |
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| Gold Coast University Hospital | Recruiting | Southport | Queensland | 4215 | Australia |
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| The Royal Adelaide Hospital | Recruiting | Adelaide | South Australia | 5000 | Australia |
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| The Alfred Hospital | Recruiting | Melbourne | Victoria | 3004 | Australia |
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| The Austin Hospital | Not yet recruiting | Melbourne | Victoria | 3084 | Australia |
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| Monash Medical Centre | Not yet recruiting | Melbourne | Victoria | 3168 | Australia |
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| The Royal Melbourne Hospital | Recruiting | Parkville | Victoria | 3050 | Australia |
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| ID | Term |
|---|---|
| D002543 | Cerebral Hemorrhage |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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