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

Stroke Clinical Trial

— EVACUATE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04434807
• Other study ID #: MBC2001
• Status: Recruiting
• Phase: N/A
• Start date: November 15, 2020
• Est. completion date: December 2026

Study information

• Verified date: October 2021
• Source: University of Melbourne
• Contact: Melbourne Brain Centre at the Royal Melbourne Hospital
• Phone: +61 3 9342 4424
• Email: info[@]thembc.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• 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)

Locations

Country	Name	City	State
Australia	The Royal Adelaide Hospital	Adelaide	South Australia
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	The Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Austin Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Liverpool Hospital	Sydney	New South Wales
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
University of Melbourne

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Safety: Hematoma growth or reaccumulation at 24 hours	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
Other	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
Other	Patient Reported Outcomes Measurement Information System (PROMIS10)		6 and 12 months post-stroke
Other	Modified Rankin Scale (mRS) 0-2, 0-3, ordinal and utility-weighted analysis at 12 months		12 months post-stroke
Other	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
Other	Length of stay in intensive care unit, acute hospital, acute hospital and rehabilitation		6 months post-stroke
Other	Home time - time spent at home in the first 6 months		6 months post-stroke
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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