Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000668808
Ethics application status
Approved
Date submitted
30/03/2021
Date registered
1/06/2021
Date last updated
21/07/2024
Date data sharing statement initially provided
1/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of two existing transfer options: expedited transfer versus non-expedited transfer from scene to hospital in of out of hospital cardiac arrest patients treated and the impact on survival.
Scientific title
A randomised controlled trial on survival in Out of Hospital Cardiac Arrest patients treated with two existing transfer options: expedited transfer versus non-expedited transfer from scene to hospital – The EVIDENCE Study.
Secondary ID [1] 303489 0
None
Universal Trial Number (UTN)
Trial acronym
Efficacy and Value In ExpeDited out of hospital arrEst care with End tidal CO2 (ETCO2) ECMO CPR (ECPR) – The EVIDENCE Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac arrest 320806 0
Condition category
Condition code
Cardiovascular 318627 318627 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Expedited transfer (after 15 minutes of professional paramedic resuscitation) with Mechanical Cardiopulmonary Resuscitation (MCPR) and emergent coronary angiography with or without Extracorporeal Membrane Oxygenation CPR (ECPR). Intensive care paramedics will deliver the intervention and participants will be randomised on scene using the REDCap application. A short survey will be completed and patients will be randomised (1:1) to the control arm (standard protocols and extended on scene resuscitation) or the expedited arm (aim to transport participants off scene within 15 minutes of commencement of CPR). The duration of on site resuscitation and transport from scene is recorded in the NSW Ambulance case sheet, and will be transcribed into the secure REDCap database. Duration of the study is 2.5 years.
Intervention code [1] 319778 0
Treatment: Other
Comparator / control treatment
Non-expedited transfer (more extended on scene resuscitation, up to 30 minutes or greater depending on the situation) from scene with MCPR, coronary angiography with or without ECPR.
Control group
Active

Outcomes
Primary outcome [1] 326584 0
To assess the efficacy of expedited OHCA care against non-expedited cardiac arrest care with regards to survival with favourable neurological outcome as defined by cerebral performance category (CPC) 1 or 2. This outcome will be stratified by initial rhythm (VT/VF and PEA).
Timepoint [1] 326584 0
From admission to hospital discharge
Secondary outcome [1] 391985 0
Overall survival with CPC score 1-2 at 6 months post arrest with expedited versus non-expedited transfer protocol. This will also be stratified by initial rhythm (VT/VF and PEA)
Timepoint [1] 391985 0
6 months post cardiac arrest.
Secondary outcome [2] 396217 0
Survival with CPC score 1-2 at discharge and at 6 months of those receiving MCPR + coronary angiography only versus those receiving MCPR, ECPR and coronary angiography.
Timepoint [2] 396217 0
At hospital discharge and 6 months post cardiac arrest.
Secondary outcome [3] 396218 0
Survival with CPC score 1-2 at discharge and at 6 months by time of day of arrest – 0700-1800 hr versus 1800-0700 hr.
Timepoint [3] 396218 0
At hospital discharge and 6 months post cardiac arrest.
Secondary outcome [4] 396219 0
Overall survival with CPC score 1-2 at discharge by ECPR eligibility.
Timepoint [4] 396219 0
At hospital discharge post cardiac arrest.
Secondary outcome [5] 396220 0
ROSC by ETCO2 10-20 mmHg, 20-30 mmHg and >30 mmHg on arrival to emergency department. ETCO2 will be assessed by capnography.
Timepoint [5] 396220 0
On arrival to emergency department post cardiac arrest.
Secondary outcome [6] 396221 0
Survival by ETCO2 10-20 mmHg, 20-30 mmHg and >30 mmHg on arrival to emergency department. ETCO2 will be assessed by capnography.
Timepoint [6] 396221 0
On arrival to emergency department post cardiac arrest.
Secondary outcome [7] 396222 0
Neurological outcome and Quality of Life (QoL) analysis at 4 weeks and 6 months post-randomisation, using the Euroqol 5-dimension 5 level preference-based measure of health (EQ-5D-5L), and the rapid Montreal Cognitive Assessment instrument (MoCA-BLIND). This is a composite secondary outcome.
Timepoint [7] 396222 0
At 4 weeks and at 6 months post cardiac arrest.
Secondary outcome [8] 396223 0
Safety: Number of complication rates assigned to MCPR and ECPR. This will be assessed by review of medical records.
Timepoint [8] 396223 0
Following randomisation and during hospital admission.
Secondary outcome [9] 396224 0
Effect on ambulance transfer times and arrest to ECMO flow times. This will be analysed at the end of the study using temporal and spatial modelling. Naïve travel times from every suburb to every hospital will be measured via Google Maps API and validated against car manufacturer data to map access to hospitals across NSW. In order to understand the probabilistic performance of the traffic network, distributions of site-to-hospital travel times occurring at the same time of day and day of week as historical OHCAs are collected. The distribution allows the team to report on which patients could have reached potential hospitals within the time budget with a confidence level provided by the repeated observations
Timepoint [9] 396224 0
From randomisation and during hospitalisation.
Secondary outcome [10] 396225 0
Change in participant transfer numbers pre (historical cardiac arrest registry data) and during the study. This will be assessed by comparing numbers in the cardiac arrest registry.
Timepoint [10] 396225 0
Pre study and duration of the study.
Secondary outcome [11] 396226 0
Determine the cost of delivering OHCA care either expedited or non-expedited.
Timepoint [11] 396226 0
Following study completion. At hospital discharge. Participant “costs” will be defined as the sum of money attributed to their episode of care across all elements from time of cardiac arrest to hospital discharge. Key elements attributed to the participants care from time of cardiac arrest to hospital discharge or death will be assessed. Unit costs will be sourced from the appropriate AR-DRG, state cost of care standards, the Australian Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) consistent with standards for health economic evaluation in Australia

Eligibility
Key inclusion criteria
1. Non-traumatic out of hospital cardiac with suspected medical cause
Note: Only non-traumatic cardiac arrests will be included, traumatic cardiac arrests such as blunt traumatic body injury from any cause e.g. motor vehicle collision will not be included. Drownings will be included providing they meet all other inclusion criteria.

2. MCPR present and all of the following
a. Estimated age 18-70 years.
b. Witnessed OHCA.
c. Initial rhythm VT/VF or automatic external defibrillator (AED) shock delivered or PEA arrest.
d. Bystander CPR started within <5 minutes and ongoing on ambulance arrival with no history suggestive of a prolonged period without CPR.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A traumatic cardiac arrest including blunt traumatic body injury from any cause e.g. hanging, motor vehicle accident.
2. Asystole as first rhythm.
3. Terminal illness (including end-stage heart, lung disease or malignancy).
4. Current advance care directive limiting treatment.
5. Advanced cognitive impairment e.g. dementia.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur using a secure REDCap application on arrival to the scene of arrest by the intensive care paramedic.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis will be a comparison of survival at discharge with CPC 1 or 2 after randomisation between the two arms. Results will be stratified by initial rhythm (VT/VF versus PEA). The primary analysis will be a relative risk in all-cause mortality + survival with a CPC score >2, with a 95% CI and p-value. Additionally, a risk difference and number needed to treat (NNT) will be calculated. Similarly, these same analyses will be undertaken for all-cause mortality at 6 months. Kaplan–Meier curves for all-cause mortality will be produced. Hazard ratios will be presented from Cox proportional hazards modelling. Ordered logistic regression will be used to compare the two treatments and a trend test computed. Intention-to-treat analysis will be performed as the primary statistical method; this includes all randomised participants in the groups to which they were randomly assigned, regardless of their adherence with the entry criteria, treatment they actually received and deviation from the protocol. Two-sided p-values will be used for all superiority testing. All statistical analyses shall be performed using SAS software. A limited number of pre-planned subgroup analyses on the primary endpoint will be undertaken which will be detailed in the statistical analysis plan. Analyses will be completed using logistic regression and a formal test undertaken by including an interaction term between the characteristic and the intervention.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/07/2021
Actual
28/07/2021
Date of last participant enrolment
Anticipated
1/07/2023
Actual
27/02/2024
Date of last data collection
Anticipated
27/08/2024
Actual
Sample size
Target
250
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18740 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 18741 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 18742 0
Westmead Hospital - Westmead
Recruitment hospital [4] 18743 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 18744 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 18745 0
Prince of Wales Hospital - Randwick
Recruitment hospital [7] 18746 0
St George Hospital - Kogarah
Recruitment hospital [8] 18747 0
Blacktown Hospital - Blacktown
Recruitment hospital [9] 18748 0
Nepean Hospital - Kingswood
Recruitment hospital [10] 18749 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [11] 18941 0
Wollongong Hospital - Wollongong
Recruitment hospital [12] 18942 0
The Northern Beaches Hospital - Frenchs Forest
Recruitment hospital [13] 19592 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [14] 19593 0
Concord Repatriation Hospital - Concord
Recruitment hospital [15] 19594 0
The Sutherland Hospital - Caringbah
Recruitment postcode(s) [1] 33184 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 33185 0
2050 - Camperdown
Recruitment postcode(s) [3] 33186 0
2145 - Westmead
Recruitment postcode(s) [4] 33187 0
2170 - Liverpool
Recruitment postcode(s) [5] 33188 0
2065 - St Leonards
Recruitment postcode(s) [6] 33189 0
2031 - Randwick
Recruitment postcode(s) [7] 33190 0
2217 - Kogarah
Recruitment postcode(s) [8] 33191 0
2148 - Blacktown
Recruitment postcode(s) [9] 33192 0
2747 - Kingswood
Recruitment postcode(s) [10] 33193 0
2560 - Campbelltown
Recruitment postcode(s) [11] 33450 0
2500 - Wollongong
Recruitment postcode(s) [12] 33451 0
2086 - Frenchs Forest
Recruitment postcode(s) [13] 34200 0
2200 - Bankstown
Recruitment postcode(s) [14] 34201 0
2139 - Concord
Recruitment postcode(s) [15] 34202 0
2229 - Caringbah

Funding & Sponsors
Funding source category [1] 307906 0
Government body
Name [1] 307906 0
NSW Ministry of Health
Country [1] 307906 0
Australia
Primary sponsor type
University
Name
University of Sydney/NHMRC CTC
Address
NHMRC Clinical Trials Centre, Medical Foundation Building, 92-94 Parramatta Road, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 308619 0
None
Name [1] 308619 0
Address [1] 308619 0
Country [1] 308619 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307905 0
Sydney Local Health District Ethics Review Committee, RPAH Zone
Ethics committee address [1] 307905 0
Ethics committee country [1] 307905 0
Australia
Date submitted for ethics approval [1] 307905 0
29/03/2021
Approval date [1] 307905 0
23/04/2021
Ethics approval number [1] 307905 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108882 0
Dr Mark Dennis
Address 108882 0
Royal Prince Alfred Hospital, Sydney Local Health District, Missenden Rd, Camperdown, NSW, 2050
Country 108882 0
Australia
Phone 108882 0
+61 400 701 265
Fax 108882 0
Email 108882 0
[email protected]
Contact person for public queries
Name 108883 0
Mark Dennis
Address 108883 0
Royal Prince Alfred Hospital, Sydney Local Health District, Missenden Rd, Camperdown, NSW, 2050
Country 108883 0
Australia
Phone 108883 0
+61 400 701 265
Fax 108883 0
Email 108883 0
[email protected]
Contact person for scientific queries
Name 108884 0
Mark Dennis
Address 108884 0
Royal Prince Alfred Hospital, Sydney Local Health District, Missenden Rd, Camperdown, NSW, 2050
Country 108884 0
Australia
Phone 108884 0
+61 400 701 265
Fax 108884 0
Email 108884 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIImproving access to extracorporeal membrane oxygenation for out of hospital cardiac arrest: pre-hospital ECPR and alternate delivery strategies2022https://doi.org/10.1186/s13049-022-01064-8
EmbaseA randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest: Rationale and design of the EVIDENCE trial.2024https://dx.doi.org/10.1016/j.ahj.2023.10.003
N.B. These documents automatically identified may not have been verified by the study sponsor.