Intra Cerebral Hemorrhage, Stroke
Conditions
Keywords
neurosurgery, minimally invasive
Brief summary
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).
Interventions
Neurosurgery performed via burr hole or minicraniotomy and using the Aurora surgiscope and evacuator (Integra Lifesciences)
Sponsors
University of Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Intervention model description
Patients will receive either minimally invasive hematoma evacuation or standard medical therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with an acute supratentorial intracerebral hemorrhage (ICH) ≥20mL in volume 2. Age ≥18 years 3. Surgery can commence within 8 hours of symptom onset (the time the patient was last known to be well) or, in patients with wake-up onset, within 8 hours of the time the patient awoke with symptoms. Patients presenting with small ICH (volume \<20mL) with clinical deterioration judged due to ICH hematoma expansion meeting volume criteria may be randomized if surgery can commence within 8 hours of clinical deterioration 4. Moderate neurological deficit (NIHSS≥6) 5. Pre-stroke mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week). 6. CTA or MRA is performed and does not show an underlying vascular lesion
Exclusion criteria
1. Brainstem ICH 2. ICH secondary to trauma, where brain injury is judged more likely to be due to the broad effects of trauma rather than the focal ICH. 3. Hereditary or acquired hemorrhagic diathesis or coagulation factor deficiency (in liver disease, INR\>1.4). 4. Platelet count \<75,000 5. Unreversible heparinization or anticoagulation. If reversing warfarin, INR should be ≤1.4 before procedure commences. Reversal of heparin by protamine, dabigatran by idarucizumab and rivaroxaban, apixaban and enoxaparin by andexanet (where available) is permitted. Unreversed anticoagulation with a last dose within 48 hours is an exclusion. 6. Recent (\<12 hours) parenteral GPIIb/IIIa antagonist. 7. Recent (\<1 hour) thrombolysis. If the ICH has occurred between 1 and 12 hours following thrombolysis, cryoprecipitate (1U per 10kg) and tranexamic acid must be administered prior to treatment. 8. Participation in any investigational study in the last 30 days 9. Pregnant women (clinically evident) 10. Co-morbidities or advance care directive preventing general anaesthesia for the procedure. 11. Known terminal illness such that the patients would not be expected to survive a year. 12. Planned withdrawal of care or comfort care measures. 13. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dichotomized Modified Rankin Scale Score 0-3 vs. 4-6 at 6 months post-onset (Adjusted) | 6 months post-stroke | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dichotomized Modified Rankin Scale Score 0-2 or no change from baseline vs. 3-6 at 6 months post-onset (adjusted) | 6 months post-stroke | 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 |
| Ordinal analysis of Modified Rankin Scale Score at 6 months post-onset (adjusted) | 6 months post-stroke | 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 |
| Utility-weighted analysis of Modified Rankin Scale Score at 6 months post-onset (adjusted) | 6 months post-stroke | 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 |
| Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted) | 24 hours post-randomization | Reduction in hematoma volume at 24 hours \>70% or \<15mL residual volume, adjusted for immediate pre-treatment ICH volume |
| Proportion of patients with early neurological improvement at 7 days (adjusted) | 7 days post-stroke | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Quality of Life (EQ5D) at 12 months | 12 months post-stroke | Assessment of Quality of Life (EQ5D) at 12 months (mapped to mRS at baseline) |
| Home time - time spent at home in the first 6 months | 6 months post-stroke | — |
| Length of stay in intensive care unit, acute hospital, acute hospital and rehabilitation | 6 months post-stroke | — |
| Safety: Death due to any cause at 6 months (adjusted) | 6 months post-stroke | Death due to any cause at 6 months, adjusted for age, baseline GCS, immediate pre-treatment ICH volume and immediate pre-treatment IVH volume. |
| Safety: Hematoma growth or reaccumulation at 24 hours | 24 hours post-randomization | 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. |
| Intermediate outcome measure (primary outcome measure for Phase 2b component): Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted) | 24 hours post-randomization | 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 |
| 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 | — |
Countries
Australia
Contacts
Primary ContactMelbourne Brain Centre at the Royal Melbourne Hospital
Outcome results
None listed