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Trial registered on ANZCTR


Registration number
ACTRN12619001748101
Ethics application status
Approved
Date submitted
3/12/2019
Date registered
10/12/2019
Date last updated
10/12/2019
Date data sharing statement initially provided
10/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
EVACUATE-pilot - Ultra-Early, minimally inVAsive intraCerebral haemorrhage evacUATion versus standard trEatment (EVACUATE)-Pilot phase
Scientific title
Ultra-Early, minimally inVAsive intraCerebral haemorrhage evacUATion versus standard trEatment (EVACUATE)-Pilot phase

A phase IIa pilot feasibility study of ultra-early minimally invasive haematoma evacuation within 12 hours of intracerebral haemorrhage
Secondary ID [1] 297707 0
none
Universal Trial Number (UTN)
Trial acronym
EVACUATE-Pilot
Linked study record

Health condition
Health condition(s) or problem(s) studied:
stroke 312029 0
Condition category
Condition code
Stroke 310597 310597 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Positioning and planning
Using standard of care volumetric imaging, a line is extended through the long axis of the clot to the nearest skull surface to maximize hematoma access in a single dimension while minimizing the traversed brain, and avoiding prominent vasculature and the corticospinal tract. Approaches must avoid eloquent brain regions including the primary motor and sensory cortices, language regions, and visual cortex. Stereotactic guidance must be used during the procedure for preoperative trajectory planning and intraoperative live navigation.
Surgical Approach
A linear incision is made in the skin and a high-speed or perforator drill is used to create a 1-2 cm diameter craniectomy. When the trajectory is not perfectly perpendicular to the skull, extra care must be taken to drill away a cylinder in the bone along the planned trajectory to maximize mobility of the sheath and endoscope within the craniectomy. Hemostasis is attained with bone wax, gel foam, and bipolar cautery. Prior to dural incision, ultrasound may be used to confirm the haematoma size and location for comparison after evacuation. The dura is incised and cauterized. The pia is incised. A brain biopsy may be performed for diagnostic purposes. The pia is then cauterized and hemostasis is achieved prior to passing the Surgiscope into the hematoma.
The trajectory is planned such that the tip of the surgiscope obdurator will rest 1-2 cm from the distal end of the hematoma. The surgiscope is passed along the preplanned trajectory under live stereotactic guidance. The clear obdurator will show the red color of the clot as the surgiscope passes through it. The obdurator is then removed.
The Aurora evacuator is introduced and clot is aspirated. Irrigation can be activated through the evacuator to improve visibility of the clot-brain border and to localize bleeding vessels. If a bleeding vessel is identified, bipolar cautery is used to cauterize the vessel under direct visualization. Given the inflammatory consequence of using thrombin in the cavity, the use of thrombin in the cavity is strongly discouraged.
After hematoma is aspirated, reduced mass effect causes the surrounding brain to collapse inward and come into view at the end of the sheath. Once this occurs, the sheath is gently pivoted at the same depth to explore laterally to the sides of the hematoma cavity. Once the operator is convinced there is no remaining hematoma at that depth, the sheath is drawn back 1-2cm and the process is repeated. If, during this phase, a solid clot is encountered, the Aurora agitator is activated to digest more fibrous clot pieces. A large gauge suction and bipolar cautery may also be used if the Aurora evacuator is unable to aspirate a large clot fragment.
After clearing all visible clots by withdrawing incrementally from the distal end of the hematoma, the cavity may be irrigated heavily with lactated Ringer’s solution to evaluate for residual clot fragments and active bleeding vessels.
Assessment and closure
After aspiration of all visible clots, the device is removed and the burr hole ultrasound may be used to assess for residual haematoma. The ultrasound may be helpful to reassess the degree of evacuation and settle any doubt about questionable regions seen through the surgiscope. An intraoperative CT is then performed to confirm that the goal of residual hematoma less than or equal to 15 ml or <50% of initial haematoma volume has been achieved. If the CT demonstrates that the residual clot volume is greater than 15 ml or >50% of initial haematoma volume then a second pass for additional clot removal is recommended (followed by an additional CT scan post procedure). A third pass is not recommended. Intraoperative CT scans can either be performed in operating room or angiography suite prior to closure or it can be performed in a traditional CT scanner with the operating room remaining sterile to permit return to the OR if the evacuation is not satisfactory.
After completing the evacuation, hemostasis of the brain surface at the craniectomy site is confirmed. Dural substitute can be used at the preference of the surgeon. A titanium plate is used to cover the craniectomy defect and secured in place with titanium screws. The galea and skin are closed with sutures or staples per surgeon preference.
Intervention code [1] 313950 0
Treatment: Surgery
Intervention code [2] 313951 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319439 0
The proportion of patients with a positive response defined as at least 50% of haematoma volume removal at 24 hour CT scan compared with baseline imaging, as measured by planimetry volumetric analysis.
Timepoint [1] 319439 0
24 hours post-surgical completion
Primary outcome [2] 319440 0
Primary safety outcome - • The proportion of patients with significant haematoma reaccumulation at 24 hour follow-up CT scan (defined as either an increase in haematoma volume between post-operative and 24 hour scans of >100% and >10ml, or haematoma volume on the follow-up scan which exceeds admission volume)
Timepoint [2] 319440 0
24 hours post-surgical completion
Secondary outcome [1] 368210 0
Mean percentage haematoma removal at 24 hour CT scan
Timepoint [1] 368210 0
24 hours post-surgical completion
Secondary outcome [2] 368211 0
Mean percentage haematoma removal at post-operative CT scan
Timepoint [2] 368211 0
As soon as possible post-surgical completion
Secondary outcome [3] 368212 0
Percent of ICH subjects with < 15 cc clot (or >50% of initial volume) remaining on CT scan post endoscopic clot removal
Timepoint [3] 368212 0
As soon as possible post-surgical completion
Secondary outcome [4] 368213 0
Mean percentage haematoma removal at post-operative intracranial ultrasound (if performed)
Timepoint [4] 368213 0
As soon as possible post-surgical completion
Secondary outcome [5] 368214 0
Last known well time to commencement of procedure time (minutes, entered into study specific form)
Timepoint [5] 368214 0
Commencement of procedure
Secondary outcome [6] 368215 0
Procedure duration (in minutes, entered into study specific form)
Timepoint [6] 368215 0
End of procedure
Secondary outcome [7] 368216 0
Surgical complications (examination of medical records and surgeon self-report)
Timepoint [7] 368216 0
Discharge or 7 days (whichever is sooner)
Secondary outcome [8] 368217 0
Modified Rankin Score
Timepoint [8] 368217 0
3 and 6 months post-admission date
Secondary outcome [9] 368218 0
Mortality
Timepoint [9] 368218 0
3 and 6 months post-admission date

Eligibility
Key inclusion criteria
1. Patients presenting with an acute spontaneous supratentorial ICH >=20mL in volume
2. Age greater than or equal to 18 years
3. Surgery can commence within 12 hours of symptom onset (or in patients with unknown time of symptom onset, the time patient was last known to be well) OR in patients presenting with small ICH (volume <20mL) with clinical deterioration judged due to ICH haematoma expansion meeting volume criteria, within 12 hours of clinical deterioration
4. Moderate to severe neurological deficit (NIHSSgreater than or equal to 6)
5. CTA or MRA is performed and does not show an underlying vascular lesion
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Glasgow coma scale (GCS) of 3 unless procedure can be commenced within 1 hour of deterioration to this level
2. Brainstem ICH (minimal brainstem extension of a thalamic ICH is allowed)
3. 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,
4. Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency (in liver diease, INR>1.5).
5. Platelet count <75,000
6. Unreversed heparinization or anticoagulation. An INR or less than 1.6 is required in the setting of reversed warfarinisation. 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.
7. Recent (<12 hours) parenteral GPIIb/IIIa antagonist.
8. Recent (<1 hour) thrombolysis. If the ICH has occurred between 1 and 12 hours following thrombolysis cryoprecipitate (1U per 10kg) must be administered prior to treatment.
9. Participation in any investigational study in the last 30 days
10. Known terminal illness such that the patients would not be expected to survive a year.
11. Planned withdrawal of care or comfort care measures.
12. 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Simon's two-stage design will be used. In the first stage, 5 patients will be recruited, with a potential to recruit 5 more patients in the second stage to the total of 10 patients.

The null hypothesis that the response rate is 0.2 will be tested against a one-sided alternative. During Stage 1, if 1 or none of the 5 patients achieve a positive response, the study will be stopped. Otherwise, 5 additional patients will be accrued during Stage 2 for a total sample size of 10, and the null hypothesis will be rejected if 5 or more patients in total will achieve a positive response. This design yields a Type I error rate of 0.03 and power of 0.8 when the true response rate is 0.6.
All outcomes will be estimated as either proportion or mean as appropriate and presented with corresponding 95% confidence intervals.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 13404 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 13405 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 26007 0
5000 - Adelaide
Recruitment postcode(s) [2] 26008 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 302231 0
Hospital
Name [1] 302231 0
Royal Adelaide Hospital
Address [1] 302231 0
1 Port Road Adelaide SA 5000
Country [1] 302231 0
Australia
Funding source category [2] 304488 0
Hospital
Name [2] 304488 0
Royal Melbourne Hospital
Address [2] 304488 0
300 Grattan St, Parkville VIC 3050
Country [2] 304488 0
Australia
Primary sponsor type
Hospital
Name
royal adelaide hospital
Address
1 Port Road Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 302096 0
None
Name [1] 302096 0
Address [1] 302096 0
Country [1] 302096 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302911 0
Central northern Adelaide Local Health Network REC
Ethics committee address [1] 302911 0
1 Port Road Adelaide SA 5000
Ethics committee country [1] 302911 0
Australia
Date submitted for ethics approval [1] 302911 0
13/03/2019
Approval date [1] 302911 0
06/05/2019
Ethics approval number [1] 302911 0
HREC/19/CALHN/151

Summary
Brief summary
This trial is a phase IIa study of ultra-early minimally invasive haematoma removal acutely following ICH. The aim of the study is to demonstrate feasibility, safety and preliminary efficacy of this treatment in patients with acute intracerebral supratentorial haemorrhage of greater than 20mL volume and less than 12 hours duration.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91818 0
A/Prof Timothy Kleinig
Address 91818 0
Dept Neurology, Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Country 91818 0
Australia
Phone 91818 0
+61421832272
Fax 91818 0
Email 91818 0
timothy.kleinig@sa.gov.au
Contact person for public queries
Name 91819 0
A/Prof Timothy Kleinig
Address 91819 0
Dept Neurology, Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Country 91819 0
Australia
Phone 91819 0
+61421832272
Fax 91819 0
Email 91819 0
timothy.kleinig@sa.gov.au
Contact person for scientific queries
Name 91820 0
A/Prof Timothy Kleinig
Address 91820 0
Dept Neurology, Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Country 91820 0
Australia
Phone 91820 0
+61421832272
Fax 91820 0
Email 91820 0
timothy.kleinig@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All trial data will be publicly available in a de-identified format
When will data be available (start and end dates)?
From 16.12.20 until no end date determined
Available to whom?
To interested researchers
Available for what types of analyses?
For meta-analyses
How or where can data be obtained?
By contacting the Principal investigator via email (timothy.kleinig@sa.gov.au)
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 6006 0
Study protocol
Citation [1] 6006 0
Link [1] 6006 0
Email [1] 6006 0
timothy.kleinig@sa.gov.au
Other [1] 6006 0
Attachment [1] 6006 0
Summary results
No Results