Stay or go? Should we Move Patients with Refractory Out-of-Hospital Cardiac Arrest to Hospital? The EVIDENCE Trial

Background

This is great to see. A randomised controlled trial in prehospital care that actually aims to answer a really important and super controversial question. When we have an out-of-hospital cardiac arrest (OHCA) where initial resuscitation efforts fail, should we then transport to hospital for further treatment/therapies or should we stay and keep going with the available ALS techniques we have. In the UK there is quite a lot of variability around this, in Virchester we have high than expected rates of transport whilst still in cardiac arrest as compared to other areas, but is that right, with right being some idea of whether it leads to better outcomes for patients?

Whether to continue resuscitation on scene or expedite transport to hospital for advanced therapies has long been debated. You may hear the phrase ‘stay and play, or load and go’ if you do then close your ears…. It’s not a helpful phrase and over-simplifies the question as it’s often nuanced by patient characteristics, geography and an understanding of what therapies are available on scene vs. hospital. Observational studies have provided conflicting signals. Data from the Resuscitation Outcomes Consortium (ROC) registry suggested that intra-arrest transport was associated with lower survival compared to continued on-scene resuscitation (1). Conversely, Dutch registry data suggested a possible benefit if transport occurred within 20 minutes (2). There are often significant confounding factors in observational studies and so we could really do with better trial design, such as RCTs

One of the big factors will be what therapies are available if a move to hospital is undertaken. If your system is going to carry on with the same ALS algorithm but just in a different place, it;’s unlikely to make much of a difference, but if you can move to more advanced therapies such as ECPR, intra-arrest PCI etc. then there may be a difference.

The ARREST trial in the US, though very small, suggested benefit from ECPR (3). The Prague OHCA trial randomised 256 patients and found no statistically significant improvement with expedited ECPR and angiography (4). The INCEPTION trial in the Netherlands (n=160) also failed to show a benefit for ECPR over conventional resuscitation (5). Some of these were OOH thereapies, others in hospital, but the picture is really mixed and complicated by geographical and other matters.

Against this backdrop of uncertainty, the EVIDENCE trial (6) was launched in Sydney, Australia, to test whether expedited transport improves outcomes compared with extended on-scene resuscitation. The abstract is below, but as always ensure that you read the paper yourself and come to your own conclusions.

Abstract

The benefit of expedited intra-arrest transport with ongoing resuscitation versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest (OHCA) is uncertain. We aimed to determine whether expedited intra-arrest transfer to hospital in adults with refractory OHCA improves favourable neurological outcomes.

Methods

We conducted a prospective, parallel, multi-centre, open-label randomised, superiority trial across greater Sydney, NSW, Australia. Patients aged 18–70 years with a witnessed OHCA of presumed medical cause, bystander cardiopulmonary resuscitation (CPR), and an initial shockable rhythm or pulseless electrical activity without return of spontaneous circulation after 15 mins of advanced life support or three rounds of professional resuscitation were randomly assigned (1:1) at the scene by New South Wales Ambulance paramedics using a secure online randomisation system. Masking of allocation from ambulance staff and hospital staff receiving the patients was not possible. The intervention consisted of a predefined expedited bundle of pre-hospital care followed by intra-arrest transport with mechanical compression to a cardiac catheterisation centre (15 receiving hospitals) for immediate assessment for coronary angiography, extracorporeal cardiopulmonary resuscitation (ECPR), or both. The control arm consisted of a standard transport strategy of more extended on-scene advanced life support before considering transport and the same therapies. The primary outcome was survival with a good neurological outcome (defined as Cerebral Performance Category [CPC] score of 1–2) at hospital discharge, stratified by initial rhythm. Patients were followed-up until death or for 6 months (last patient followed-up Aug 29, 2024). All analyses were done on an intention-to-treat basis. The trial was prospectively registered with the Australian Clinical Trials Registry, ACTRN12621000668808 and is now complete. Data on safety and adverse events were collected throughout the study period and reported to a data safety monitoring board on a 6 monthly basis.

Findings

Between July 15, 2021 and March 3, 2024, we enrolled 206 patients. Eight patients were later deemed to be ineligible and one patient was excluded due to a randomisation application failure. 197 patients were therefore enrolled; 102 to the expedited strategy (intervention) and 95 to the standard strategy (control). The median age was 57·0 years (range 47–64); 161 (82%) were men and 78 (40%) were White. At hospital discharge, 15 (15%) of 102 patients in the expedited transportation group were alive with a favourable neurological outcome, compared with 15 (16%) of 95 patients in the standard care group (risk difference –1·1% [95% CI –12·2% to 10·0%]; adjusted relative risk 0·95 [95% CI 0·50 to 1·8], p=0·87). 38 patients had a serious adverse event (19%)—35 (92%) were diagnosed with a hypoxic brain injury (17 [49%] in the expedited arm, 18 [51%] in the standard arm), one (3%) had a cerebral stroke, one (3%) had a pulmonary haemorrhage, and one (3%) had a gastrointestinal haemorrhage (all in the standard arm). Adverse events were evenly distributed between treatment arms. No unanticipated (ie, expected sequelae seen in a cardiac arrest trial or in intensive care) adverse events were identified.

Interpretation

Among patients with refractory out-of-hospital cardiac arrest, expedited intra-arrest transport did not significantly improve survival with neurologically favourable outcome. However, the study might have been underpowered to detect a smaller than expected treatment effect.

What kind of study is this

The EVIDENCE trial was a multicentre, parallel-group, open-label, superiority randomised controlled trial. Pretty much exactly what we want to see here. RCTs are the best way to try and control for bias and get us closer to the truth. Alongside the ambulance service, fifteen receiving hospitals in Sydney, including five ECPR centres, participated (Ed – that’s more ECPR centres then in the entirety of the UK, and there is currently no ECPR in the whole of Virchester (frustratingky)). Randomisation occurred in the field via a smartphone tool after 15 minutes of advanced life support without ROSC, which is the definition of refractory arrest here.

Patients were allocated to either:

Expedited transport: a predefined bundle of short on-scene care followed by intra-arrest transfer with mechanical CPR to hospital for possible angiography and/or ECPR.
Standard care: prolonged advanced life support on scene, with transport only considered later.

The primary outcome was survival with good neurological function (CPC 1–2) at hospital discharge. Secondary outcomes included survival and neurological outcomes at 4 weeks and 6 months, as well as rates of ROSC, angiography, PCI, ECPR, and complications. These are pretty reasonable outcomes and they did follow up in the secondary outcomes to 6 months.

Tell me about the patients

From July 2021 to March 2024, 197 patients were randomised. The median age was 57 years, 82% were men, and nearly all arrests were witnessed with bystander CPR provided. Three-quarters had a shockable rhythm (VF/VT), with the remainder in PEA.

They excluded patients in Asystole which is reasonable as outcomes are known to be very poor in those patients.

Randomisation occurred a median of 21 minutes after collapse. Expedited patients left scene faster (15 minutes vs 24 minutes) and more often reached hospital within 60 minutes of arrest (66% vs 43%) (6).

Patients were carefully selected: only adults aged 18–70 years with a presumed medical cause were included. Asystole, non-medical causes (trauma, overdose), and significant comorbidities were excluded.

What were the outcomes in this study

The primary outcome was survival with CPC 1–2 at hospital discharge.

Secondary outcomes included:

Survival with CPC 1–2 at 4 weeks and 6 months
Overall survival at discharge, 4 weeks, and 6 months
Subgroup analyses (initial rhythm, age, ETCO₂ at arrival, time of day)
Access to advanced therapies (angiography, PCI, ECPR)
Adverse events (including rib fractures, hypoxic brain injury, bleeding).

What are the main results

Primary outcome: 15% survived with good neurological function in both groups (15/102 expedited vs 15/95 standard). No difference: risk difference –1.1% (95% CI –12.2 to 10.0), p=0.87 (6).
Overall survival: 19% in both groups.
By rhythm: Almost all survivors had VF/VT. Only one PEA patient survived (in the control arm).
Hospital therapies: 33% expedited vs 29% standard underwent angiography. Only 12 patients (6%) received ECMO (7 expedited, 5 standard). Two survived to discharge. Median time to ECMO flow was 80 minutes—too late to be effective in most.
Adverse events: 19% had serious adverse events, mostly hypoxic brain injury. No significant differences between groups.

In short, expedited transport was feasible and safe, but conferred no survival benefit. It also shows that it’s the shockable rhythms where success lies.

Do the results stand up to critical appraisal?

There are a lot of positivew (Strengths):

Largest multicentre trial of its kind
Pragmatic design embedded in routine EMS and hospital systems
Masked assessment of neurological outcomes
Engagement across 15 hospitals and >1300 paramedics, that’s such an achievement and a great example of good quality prehospital research.

And there are some weaknesses too (Limitations:

)It’s underpowered: They designed to detect a large treatment effect; smaller benefits could not be ruled out. 197 patient is really small when we compare it to other prehospital trials in OHCA such as the PARAMEDIC and AIRWAYS trials where thousands of patients were recruited to show important benefit. It’s worth reading the stats section about the sample size calculation as it changed during the study. That’s not ideal. Even then they were calculating for a 15% difference in outcome, which is very ambitious. Bottom line is that if small but significant differences exist then this sample size would miss them.
Delays to hospital therapies: Median time to hospital in the expedited group was 55 minutes; ECMO started at 80 minutes, this is likely too late for benefit, and reflects our experience here in Virchester when we trialled ECPR on this model (start ECPR in hospital). Remember that the alternative which is to start ECPR on scene (such as in Paris) is a different model that also needs testing in robust trials. So maybe this trial tells us that if we want to look at ECPR we need to see if we can do it at scene.
Control contamination: Many “standard” patients were transported anyway, narrowing the difference between groups. This is common in trials, and it reflects practice. But it may influence the effect size.
Resource limitations: ECPR was mostly unavailable outside business hours; so only a handful of patients received it. This is an issue as I described earlier, if you’re not transporting to do something different then why transport?
Generalisability: This may well be mostly relevant to this particular health economy, in this country and in this city. How generalisable the results are to other settings is really difficult to know, a problem we see in a lot of trials over highlky sepcailised intervention in OHCA.

Taken with Prague OHCA (4) and INCEPTION (5), EVIDENCE reinforces the message: unless hospital therapies can be delivered very rapidly, expedited transport is unlikely to help.

Should we change practice based on this study

Probably not, at least not universally. For most EMS systems, high-quality on-scene resuscitation remains the standard of care. Expedited transport only makes sense if there is realistic, timely access to advanced interventions like ECMO or PCI.

The trial does reassure us that intra-arrest transport can be delivered safely by skilled paramedics with mechanical CPR, but it is not a panacea. Systems should carefully consider their own geography, hospital capacity, and ECMO access before adopting an expedited strategy.

Summary

The EVIDENCE trial (6) tested whether expedited transport improves survival in refractory OHCA. It found no difference in survival or neurological outcome compared with extended on-scene resuscitation.

Expedited strategies may still have a role in well-resourced systems with 24/7 ECMO and cath-lab capacity, but for now, the evidence supports focusing on the basics.

References

Grunau B, Reynolds JC, Scheuermeyer FX, et al. Association between intra-arrest transport and survival to hospital discharge among out-of-hospital cardiac arrest patients. Resuscitation. 2018;125:39–44.
Bosch FH, de Graaf C, Bonnes JL, et al. Intra-arrest transport with ongoing resuscitation for refractory out-of-hospital cardiac arrest: results from a nationwide registry. Resuscitation. 2015;94:46–52.
Yannopoulos D, Bartos JA, Raveendran G, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single-centre, open-label, randomised controlled trial. Lancet. 2020;396(10258):1807–16.
Belohlavek J, Smalcova J, Rob D, et al. Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation, and immediate invasive assessment and treatment on functional neurologic outcome in refractory out-of-hospital cardiac arrest: a randomized clinical trial. JAMA. 2022;327(8):737–47.
Suverein MM, Delnoij TSR, Lorusso R, et al. Extracorporeal cardiopulmonary resuscitation in refractory out-of-hospital cardiac arrest. N Engl J Med. 2023;389:1163–73.
Burns B, Marschner IC, Buscher H, et al. Expedited transfer from the scene for refractory out-of-hospital cardiac arrest in Australia: a prospective, multicentre, open-label, randomised controlled trial (EVIDENCE). Lancet Respir Med. 2025; published online Aug 22. doi:10.1016/S2213-2600(25)00130-4.
Halden Hutchinson-Bazely, “Pre Hospital Extracorporeal CPR (ECPR) in the UK: The Sub30 study,” in St.Emlyn’s, January 2, 2025, https://www.stemlynsblog.org/sub30study/.
Simon Carley, “ECPR for refractory cardiac arrest,” in St.Emlyn’s, January 30, 2023, https://www.stemlynsblog.org/ecpr-for-refractory-cardiac-arrest/.
Prehospital ECPR with Alice Hunt: Ep 248 – Prehospital eCPR with Alice Hutin at Tactical Trauma 2024