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

Not Applicable

Recruiting

• Conditions: Intra Cerebral Hemorrhage; Stroke
• Interventions: Procedure: Minimally invasive hematoma evacuation

• Registration Number: NCT04434807
• Lead Sponsor: University of Melbourne

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 available

Study Timeline

• Study First Submitted: 2020-06-13
• Study First Submitted QC: 2020-06-13
• Study First Posted: 2020-06-17
• Study Start: 2020-11-15
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-23
• Last Update Posted: 2024-06-25
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Minimally invasive hematoma evacuation	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (13)

Prince of Wales Hospital; 🇦🇺 Sydney, New South Wales, Australia

Liverpool Hospital; 🇦🇺 Sydney, New South Wales, Australia

Westmead Hospital; 🇦🇺 Sydney, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

The Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

The Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Royal Prince Alfred Hospital; 🇦🇺 Sydney, New South Wales, Australia

John Hunter Hospital; 🇦🇺 Newcastle, New South Wales, Australia

Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

The Austin Hospital; 🇦🇺 Melbourne, Victoria, Australia

Monash Medical Centre; 🇦🇺 Melbourne, Victoria, Australia

The Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia