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

Official title

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

Overview

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

• Procedure Minimally invasive hematoma evacuation
  Neurosurgery performed via burr hole or minicraniotomy and using the Aurora surgiscope and evacuator (Integra Lifesciences)

Primary outcome measures

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

Secondary outcome measures (5)

• 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]
• Ordinal 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 post-onset (adjusted) [Time frame: 6 months post-stroke]
• Reduction in hematoma volume at 24 hours >70% or <15mL residual volume (adjusted) [Time frame: 24 hours post-randomization]
• Proportion of patients with early neurological improvement at 7 days (adjusted) [Time frame: 7 days post-stroke]

Eligibility criteria

Inclusion criteria

• Patients with an acute supratentorial intracerebral hemorrhage (ICH) ≥20mL in volume
• Age ≥18 years
• 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
• Moderate neurological deficit (NIHSS≥6)
• Pre-stroke mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
• CTA or MRA is performed and does not show an underlying vascular lesion

Exclusion criteria

• Brainstem ICH
• 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.
• Hereditary or acquired hemorrhagic diathesis or coagulation factor deficiency (in liver disease, INR>1.4).
• Platelet count <75,000
• 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.
• Recent (<12 hours) parenteral GPIIb/IIIa antagonist.
• 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.
• Participation in any investigational study in the last 30 days
• Pregnant women (clinically evident)
• Co-morbidities or advance care directive preventing general anaesthesia for the procedure.
• Known terminal illness such that the patients would not be expected to survive a year.
• Planned withdrawal of care or comfort care measures.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Australia · 13 centers

• John Hunter Hospital — Newcastle
• Prince of Wales Hospital — Sydney
• Royal Prince Alfred Hospital — Sydney
• Westmead Hospital — Sydney
• Liverpool Hospital — Sydney
• The Royal Brisbane and Women's Hospital — Brisbane
• Princess Alexandra Hospital — Brisbane
• Gold Coast University Hospital — Southport
• … and 5 more centers

Identifiers

NCT: NCT04434807 · MBC2001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗