Ultra-Early, Minimally inVAsive intraCerebral Haemorrhage evacUATion Versus Standard trEatment (EVACUATE)

• ClinicalTrials.gov Identifier: NCT04434807
• Recruitment Status: Recruiting
• First Posted: June 17, 2020
• Last Update Posted: October 25, 2021
• Sponsor: University of Melbourne
• Information provided by (Responsible Party): Bruce Campbell, University of Melbourne

Tracking Information

• First Submitted Date: June 13, 2020
• First Posted Date: June 17, 2020
• Last Update Posted Date: October 25, 2021
• Actual Study Start Date: November 15, 2020
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 13, 2020)

Dichotomized Modified Rankin Scale Score 0-3 vs. 4-6 at 6 months post-onset (Adjusted) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 13, 2020)

• Dichotomized Modified Rankin Scale Score 0-2 or no change from baseline vs. 3-6 at 6 months post-onset (adjusted) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 13, 2020)

• Safety: Death due to any cause at 6 months (adjusted) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 6 and 12 months post-stroke ]
• Modified Rankin Scale (mRS) 0-2, 0-3, ordinal and utility-weighted analysis at 12 months [ Time Frame: 12 months post-stroke ]
• Assessment of Quality of Life (EQ5D) at 12 months [ Time Frame: 12 months post-stroke ]
  Assessment of Quality of Life (EQ5D) at 12 months (mapped to mRS at baseline)
• Length of stay in intensive care unit, acute hospital, acute hospital and rehabilitation [ Time Frame: 6 months post-stroke ]
• Home time - time spent at home in the first 6 months [ Time Frame: 6 months post-stroke ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Ultra-Early, Minimally inVAsive intraCerebral Haemorrhage evacUATion Versus Standard trEatment
• Official Title: Ultra-Early, Minimally inVAsive intraCerebral Haemorrhage evacUATion Versus Standard trEatment (EVACUATE)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients will receive either minimally invasive hematoma evacuation or standard medical therapy

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.

Primary Purpose: Treatment

Condition

• Intra Cerebral Hemorrhage
• Stroke

Intervention

Procedure: Minimally invasive hematoma evacuation

Neurosurgery performed via burr hole or minicraniotomy and using the Aurora surgiscope and evacuator (Integra Lifesciences)

Study Arms

• Experimental: Minimally invasive hematoma evacuation
  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.
  Intervention: Procedure: Minimally invasive hematoma evacuation
• No Intervention: Standard care (medical therapy)
  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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 13, 2020): 240
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2026
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Melbourne Brain Centre at the Royal Melbourne Hospital; +61 3 9342 4424; info@thembc.org.au

• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04434807
• Other Study ID Numbers: MBC2001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• Time Frame: 2 years after the publication of the primary manuscript
• Access Criteria: Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA-ICH steering committee.

• Current Responsible Party: Bruce Campbell, University of Melbourne
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Melbourne
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Timothy Kleinig; Royal Adelaide Hospital/University of Adelaide
• Principal Investigator: Amal Abou-Hamden; Royal Adelaide Hospital/University of Adelaide
• Principal Investigator: 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

• PRS Account: University of Melbourne
• Verification Date: October 2021