Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001485729
Ethics application status
Approved
Date submitted
26/10/2022
Date registered
28/11/2022
Date last updated
30/05/2024
Date data sharing statement initially provided
28/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Continuous mONitoring of recovery iN acutE isChaemic sTroke (CONNECT) - Phase 1
Scientific title
Phase 1 of an investigator-initiated and conducted, multicentre, open-label study to compare the efficacy of the nuroflux device to continuously monitor and detect, abnormal brain function in patients with acute ischaemic stroke from large-vessel occlusion in the anterior circulation of the brain against the gold standard of high-intensity nursing monitoring and routine brain imaging
Secondary ID [1] 308117 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CONNECT - Phase 1
Linked study record
ACTRN12622001486718 is phase 2 follow up for this record

Health condition
Health condition(s) or problem(s) studied:
Acute Ischaemic Stroke (AIS) 328045 0
Condition category
Condition code
Neurological 325101 325101 0 0
Other neurological disorders
Stroke 325156 325156 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is for participants to wear the study device (nuroflux) as soon as possible after initial diagnostic imaging (baseline) and for at approximately 24 hours until the completion of their routine Day 1 National Institutes of Health Stroke Scale (NIHSS) assessments and brain scanning, occurring at approximately 24 hours after initial diagnostic imaging are completed. The device will be fitted, checked on, and removed by ED/Stroke ward nurses. A semi-circular ring is fitted across the participant's forehead, held in place by attachments on the sides of the device. In addition, the two ECG electrodes connected to the device are to be applied to upper chest on either side. The device will be worn continuously, and must not be removed or get wet at any point. The device is connected to a laptop wirelessly, which will be set up nearby and checked on by the ED/stroke nurse.
The investigational device is intended to provide continuous and objective metrics pertaining to the brain activity and brain blood flow of AIS patients. It is intended to provide an indication of stroke location and severity, patient response to treatment, as well as patient neurological deterioration.

Imaging, both initial and follow-up, will be either computerized tomography (CT) or magnetic resonance imaging. CT is most often used, taking a few minutes, and sometimes involving an intravenously administered iodinated contrast agent. MRI is sometimes chosen instead, taking approximately 20 mins, and sometimes utilising an intravenously administered Gadolinium-based contrast agent. The type of imaging, along with the use, specific type of contrast agent, and doses of the contrast agent, are all decisions made by clinicians completely independent from the investigators. Initial imaging, any follow-up imaging taken within 24hrs of baseline, other medical data outside of the device up to 72 hrs after baseline, and the medical data from the 90 day check-up, are all collected as part of the routine hospital diagnostic examination for AIS. While investigators will record this data, we have no influence over these procedures and these procedures not part of the introduced intervention.

Aside from wearing the device, the only other active procedure introduced as part of the intervention for the participant will be recording subjective discomfort and adverse effect information in a 24hr diary. If the participant is unable to record this information, a nurse will record this information for them. Within this study, this data will not be viewed in real-time and will not influence the decisions of clinicians. The data will only be viewed by the investigators after the 24hr device use period, comparing it’s measurements to data from other diagnostic measurements collected as a test of its accuracy.
Intervention code [1] 324777 0
Early detection / Screening
Comparator / control treatment
This study is intended to assess the accuracy of a device that is intended to screen for neurological deterioration. The data will only be viewed by the investigators after the 24hr device use period. Accuracy will be determined by comparing it’s measurements to data from other diagnostic measurements collected as a test of its accuracy (e.g neurological imaging, NIHSS assessments, etc.)
These other diagnostic measurements include:
- Brain imaging (MRI or CT) will occur immediately before study enrolment and at 24hrs after initial imaging. Additional imaging may occur at the discretion of hospital clinicians separate from study. CT scans last only a few minutes, while MRI scans take around 20 mins. Both procedures may take longer if contrast agents (dyes) are used.
- NIHSS, which is a non-invasive visual and physical assessment of stroke effect, including vision-loss, motor-loss, facial paralysis, etc. It's designed to take less than 10 mins. Data from this assessment will be collected once after Day 1 imaging.
- Glasgow Coma Scale (GCS), which is a non-invasive visual and physical assessment of consciousness, including eye, verbal, and motor responses. It's designed to take only 1-2 minutes. Data from this assessment will be assessed once after Day 1 imaging.
As a note, all imaging, along with the other diagnostic measurements outside of the intervention device, are part of the routine hospital diagnostic examination for AIS, and while investigators will collect medical data from these assessments, we have no influence over these procedures and these procedures not part of the introduced intervention.
Control group
Active

Outcomes
Primary outcome [1] 332920 0
To determine device threshold estimation on detection of neurological deterioration via comparing device measurements (Electrical brain perfusion index (EBPi), which is a combination of both electroencephalogram (EEG) and electrocardiogram (ECG) measurements, with clinical diagnostic measurements from hospital (MRI/CT imaging, NIHSS, GCS)
Timepoint [1] 332920 0
Continuously from Baseline to 24hrs
Primary outcome [2] 332921 0
To determine safety of the device when immediately deployed via medical records of adverse effects and study-specific subjective patient experience forms (only adverse effects foreseen are discomfort from wearing device).
Timepoint [2] 332921 0
Baseline, 24hrs
Primary outcome [3] 333007 0
To determine patient acceptability profile of the device when immediately deployed via study specific subjective patient experience forms.
Timepoint [3] 333007 0
Baseline, 24hrs
Secondary outcome [1] 415126 0
Device threshold estimation on severity of AIS via comparing device EBPi measurements with hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS)
Timepoint [1] 415126 0
Continuously from Baseline to 24hrs
Secondary outcome [2] 415128 0
Device threshold estimation on response to treatment (successful or unsuccessful reperfusion) via comparing device EBPi measuresments with hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS). Successful or unsuccessful reperfusion are composite and measured via the same mechanism. They are not independent.
Timepoint [2] 415128 0
Continuously from Baseline to 24hrs
Secondary outcome [3] 415129 0
Device threshold estimation on severity of recurrent stroke (defined as new lesion on follow-up imaging) via comparing device EBPi measurements with hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS)
Timepoint [3] 415129 0
Continuously from Baseline to 24hrs
Secondary outcome [4] 415130 0
Device threshold estimation on cerebral oedema via comparing device EBPi measurements with medical records and hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS)
Timepoint [4] 415130 0
Continuously from Baseline to 24hrs
Secondary outcome [5] 415537 0
Device threshold estimation on haemorrhagic transformation via comparing device EBPi measurements with medical records and hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS)
Timepoint [5] 415537 0
Continuously from Baseline to 24hrs
Secondary outcome [6] 415538 0
Device threshold estimation on early seizure (after study enrolment; defined as use of anti-convulsive drug) via comparing device EBPi measurements with medical records.
Timepoint [6] 415538 0
Continuously from Baseline to 24hrs
Secondary outcome [7] 415556 0
Device threshold estimation on location of AIS via comparing device EBPi and TCD measurements with hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS)
Timepoint [7] 415556 0
Continuously from Baseline to 24hrs
Secondary outcome [8] 415557 0
Device threshold estimation on location of recurrent stroke (defined as new lesion on follow-up imaging) via comparing device EBPi measurements with hospital diagnostic measurements (MRI/CT imaging, NIHSS, GCS)
Timepoint [8] 415557 0
Continuously from Baseline to 24hrs

Eligibility
Key inclusion criteria
1. Adults (age >= 18 years);
2. AIS (initial diagnostic scan within 24 hours from symptom onset or last known well time) in anterior circulation due to large vessel occlusion (LVO, occlusion at the internal carotid artery, the middle cerebral artery horizontal or insular segment, or proximal site of the anterior cerebral artery), diagnosed by clinician and confirmed on CT with/without angiography;
3. At least moderate neurological severity (National Institute of Health Stroke Scale [NIHSS] score >4); and
4. Provision of consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Recent (<1 months) brain surgery;
2. Evidence of seizure activity from stroke symptom onset to study inclusion;
3. Having history of severe skin rash due to ECG/EEG electrode patches;
4. Skin conditions on scalp or face that preclude safe use of the device (local infections, rashes, fragile skin, etc.);
5. Having difficulties to wear the device stably (e.g., patients with severe dementia, extreme agitation, or susceptible to stress).
6. Inability to communicate in English either personally or through translator

Study design
Purpose of the study
Diagnosis
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
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Phase 1 – Threshold estimation phase
Sample Size
Recruit 50 patients to wear the device following confirmed LVO-AIS. Assuming the distribution of device data is normal or log-normal, a sample size of 50 participants will ensure the representative of the study population asymptotically nonbiased and to have a satisfactory coverage probability.

Statistical Analysis
The final device data metric (EBPi), will be computed using EEG and ECG data captured by the device using a custom-made script written in MATLAB (MATLAB version 2019b, Mathworks Inc., Natick, MA). EEG data will also be captured and EEG metrics may be analysed in a future study. Distributions of device data, including EBPi data at each scalp electrode, by neurological deterioration, severity and location of AIS, successful reperfusion, recurrent stroke, cerebral oedema, haemorrhagic transformation, and early seizure will be calculated to estimate thresholds of primary and secondary outcomes in
Phase 1. Safety profile of the device will be analysed with descriptive statistical methods. An assessment of feasibility (as measured by patient experience and safety) and device utility (as measured by accuracy of measurements) in routine clinical practice will also be undertaken. While the sample size of this study phase (phase 1) is 50, below the required sample size of 260 for adequate power for device accuracy assessment, this sample size is adequate to gather initial data regarding the primary outcomes of device threshold estimation for detection of neurological deterioration and patient acceptability and safety before more robust data analysis can occur is Phase 2 (registered seperately).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/01/2024
Actual
18/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23456 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 38858 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 312372 0
Other Collaborative groups
Name [1] 312372 0
The George Institute
Country [1] 312372 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The George Institute
Address
Level 5, 1 King Street, Newtown NSW 2042
Country
Australia
Secondary sponsor category [1] 314115 0
None
Name [1] 314115 0
Address [1] 314115 0
Country [1] 314115 0
Other collaborator category [1] 282467 0
Commercial sector/Industry
Name [1] 282467 0
Nuroflux Pty Ltd
Address [1] 282467 0
202a/7-9 Kent Road, Mascot NSW 2020
Country [1] 282467 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311732 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 311732 0
Level 11, KGV Building Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 311732 0
Australia
Date submitted for ethics approval [1] 311732 0
27/09/2022
Approval date [1] 311732 0
31/05/2023
Ethics approval number [1] 311732 0
Protocol no. X23-0322 & 2023/ETH00608

Summary
Brief summary
Aims:
To assess the efficacy of the NurofluxTM device to continuously monitor and detect significant neurological deterioration in patients with acute ischaemic stroke due to large-vessel occlusion (LVO) in anterior cerebral circulation against the gold standard of high-intensity nursing monitoring of vital signs and neurological function, and use of routine brain imaging.

Study Design:
This is an investigator-initiated and conducted, open-label, single arm, clinical evaluation feasibility (proof-of-concept) trial. This stage is an internal pilot phase to rehearse the main study to identify key issues to consider in the next phase of the study, as well as to optimise the device parameters within the RPAH under the supervision of leading stroke clinician-scientists.

Phase 1 – Threshold estimation
RPA only. Recruit 50 patients to wear the device following confirmed AIS with LVO in the anterior circulation to estimate device threshold of critical neurological deteriorations. An assessment of device utility in routine clinical practice will also be undertaken.

Outcome Measures:
Phase 1
Primary Outcomes:
1. Device threshold estimation on detection of neurological deterioration
2. Safety and patient acceptability profile of the device when immediately deployed

Secondary Outcomes: Device threshold estimation on:
1. Acute ischaemic stroke (severity and location)
2. Response to treatment (successful or unsuccessful reperfusion)
3. Recurrent stroke
4. Cerebral oedema, haemorrhagic transformation, and early seizure (after study enrolment)

Phase 2 of this study will involve a larger sample size gathered from multiple sites for more detailed assessment of device accuracy. Phase 2 will be registered separately.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122170 0
Prof Craig Anderson
Address 122170 0
The George Institute for Global Health
Level 5, 1 King St, Newtown NSW 2042
Country 122170 0
Australia
Phone 122170 0
+61 2 8052 4521
Fax 122170 0
Email 122170 0
canderson@georgeinstitute.org.au
Contact person for public queries
Name 122171 0
Dr Xiaoying Chen
Address 122171 0
The George Institute for Global Health
Level 5, 1 King St, Newtown NSW 2042
Country 122171 0
Australia
Phone 122171 0
+61 2 8052 4549
Fax 122171 0
Email 122171 0
xchen@georgeinstitute.org.au
Contact person for scientific queries
Name 122172 0
Dr Xiaoying Chen
Address 122172 0
The George Institute for Global Health
Level 5, 1 King St, Newtown NSW 2042
Country 122172 0
Australia
Phone 122172 0
+61 2 8052 4549
Fax 122172 0
Email 122172 0
xchen@georgeinstitute.org.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?
Data dictionaries
When will data be available (start and end dates)?
From 12 month after publication of the main results, with no end date.
Available to whom?
Bona fide researchers with experience in medical research, no conflict of interest that may potentially influence their interpretation of any analyses, and employed by a recognised academic institute, health service organisation, commercial research organisation of from the pharmaceutical industry.
Available for what types of analyses?
The data sharing will be only for analyses for the purposes of health and medical research and within the constraints of the consent under which the data were originally gathered.
How or where can data be obtained?
Data can be shared with bona fide researchers after publication of the main results, based on a submitted protocol to the research office of The George Institute for Global Health, Sydney Australia. To initiate the data sharing process, please email that study PI Craig Anderson at canderson@georgeinstitute.org.au


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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