Clinical trial NCT04434807: Ultra-Early, Minimally inVAsive intraCerebral Haemorrhage evacUATion Versus Standard trEatment
Official title: Ultra-Early, Minimally inVAsive intraCerebral Haemorrhage evacUATion Versus Standard trEatment (EVACUATE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Intra Cerebral Hemorrhage
Stroke
Keywords: neurosurgery
minimally invasive
Lead sponsor: University of Melbourne
Sponsor class: OTHER
First posted: 2020-06-17
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will receive either minimally invasive hematoma evacuation or standard medical therapy
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Dichotomized Modified Rankin Scale Score 0-3 vs. 4-6 at 6 months post-onset (Adjusted)
timeFrame: 6 months post-stroke
Secondary outcomes:
measure: Dichotomized Modified Rankin Scale Score 0-2 or no change from baseline vs. 3-6 at 6 months post-onset (adjusted)
timeFrame: 6 months post-stroke
measure: Ordinal analysis of Modified Rankin Scale Score at 6 months post-onset (adjusted)
timeFrame: 6 months post-stroke
measure: Utility-weighted analysis of Modified Rankin Scale Score at 6 months post-onset (adjusted)
timeFrame: 6 months post-stroke
measure: Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted)
timeFrame: 24 hours post-randomization
measure: Proportion of patients with early neurological improvement at 7 days (adjusted)
timeFrame: 7 days post-stroke
Other outcomes:
measure: Safety: Death due to any cause at 6 months (adjusted)
timeFrame: 6 months post-stroke
measure: Safety: Hematoma growth or reaccumulation at 24 hours
timeFrame: 24 hours post-randomization
measure: Intermediate outcome measure (primary outcome measure for Phase 2b component): Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted)
timeFrame: 24 hours post-randomization
measure: Patient Reported Outcomes Measurement Information System (PROMIS10)
timeFrame: 6 and 12 months post-stroke
measure: Modified Rankin Scale (mRS) 0-2, 0-3, ordinal and utility-weighted analysis at 12 months
timeFrame: 12 months post-stroke
measure: Assessment of Quality of Life (EQ5D) at 12 months
timeFrame: 12 months post-stroke
measure: Length of stay in intensive care unit, acute hospital, acute hospital and rehabilitation
timeFrame: 6 months post-stroke
measure: Home time - time spent at home in the first 6 months
timeFrame: 6 months post-stroke
Locations:
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: The Royal Brisbane and Women's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: The Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Royal Adelaide Hospital/University of Adelaide
name: Timothy Kleinig
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Adelaide Hospital/University of Adelaide
name: Amal Abou-Hamden
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Melbourne Hospital/University of Melbourne
name: John Laidlaw
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine, Mt Sinai Hospital, New York
name: J Mocco
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine, Mt Sinai Hospital, New York
name: Christopher Kellner
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Melbourne Hospital/University of Melbourne
name: Stephen Davis
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Melbourne Hospital/University of Melbourne
name: Bruce Campbell
role: PRINCIPAL_INVESTIGATOR
References: