Clinical trial NCT03872960: A Randomised Trial of Expedited Transfer to a Cardiac Arrest Centre for Non-ST Elevation Out-of-hospital Cardiac Arrest
Official title: A Randomised Trial of Expedited Transfer to a Cardiac Arrest Centre for Non-ST Elevation Out-of-hospital Cardiac Arrest
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Out-Of-Hospital Cardiac Arrest
Keywords: cardiac arrest
pre-hospital care
strategy trial
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: King's College London
name: London School of Hygiene and Tropical Medicine
name: Barts & The London NHS Trust
name: King's College Hospital NHS Trust
name: Imperial College Healthcare NHS Trust
name: Royal Brompton & Harefield NHS Foundation Trust
name: Royal Free Hospital NHS Foundation Trust
name: St George's University Hospitals NHS Foundation Trust
name: London Ambulance Service NHS Trust
First posted: 2019-03-13
Enrollment: 862
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of ARREST is to determine the best post-resuscitation care pathway for out of hospital cardiac arrest patients without ST-segment elevation. The investigators propose that changes to emergency management comprising expedited delivery to a specialist heart attack centre with organised post-cardiac arrest care including immediate access to reperfusion therapy will reduce mortality in patients without STE compared to the current standard of care, which comprises protracted pre-hospital management of the patient without definitive care plan and delivery to geographically closest hospital.

Detailed description: Out-of-hospital cardiac arrest (OHCA) is a global public health issue. There are 60,000 cardiac arrests per year in the United Kingdom (UK), of which resuscitation is attempted in just under half. Resuscitation attempts are successful in up to 30%. However, more than two thirds of patients who survive to hospital admission die before discharge. There is wide variation in both regional and inter-hospital survival rates from OHCA; this disparity is also present across London. This variation has been shown to be attributable to hospital infrastructure, resources and personnel rather than patient characteristics. Overall survival therefore remains poor, at 7%.

It is well known that the majority of OHCA are secondary to an acute cardiac ischaemic event. Coronary artery disease is responsible for more than 70% of OHCA of presumed cardiac cause, with acute occlusion demonstrated in 50% of consecutive patients taken for immediate coronary angiography (ICA). Early cardiopulmonary resuscitation (CPR) and defibrillation, with ICA and percutaneous coronary intervention (PCI) in a cardiac arrest centre (CAC), prevents re-arrest, preserves myocardial function and has been shown to improve post-arrest outcomes in ST-segment elevation (STE). The management of patients without STE however is controversial, with a delayed approach to intervention. Despite recently published data suggesting PCI in non-STE resulted in a two-fold increase in favourable outcome, randomised data are lacking. Emergent reperfusion therapies come with a weak recommendation from the International Liaison Committee on Resuscitation (ILCOR), and a Class IIa recommendation by the American Heart Association (AHA) and European Society of Cardiology (ESC), if there is a high suspicion of ongoing infarction.

The European Association of Percutaneous Cardiovascular Interventions (EAPCI) recommends a prior rule-out of non-cardiac cause in the emergency department followed by coronary angiography within 2 hours. It remains unclear if time-critical, definitive hospital based management of the post-arrest patient without STE in a specialist centre improves outcomes, and there has been variable uptake of this strategy both pre-hospital and amongst the interventional cardiology community.

There is an urgent need for a randomised controlled trial examining the benefits of early delivery of post-cardiac arrest care in specialist centres, specifically in the absence of STE. Post-arrest care is time-critical, requires a multi-disciplinary approach and may be more optimally delivered in centres with greater provider experience. ILCOR and the EAPCI state that randomised trials are essential in this population to determine if timely delivery by the ambulance services to a CAC with organised postcardiac arrest care including immediate access to reperfusion therapy improves survival. There are no randomised trials and only indirect evidence that CAC and systems of care may be effective and only two observational studies examining the role of immediate ICA±PCI in the absence of STE. This is an important and topical question as there is a drive to regionalise care for all patients into CACs.

To address this, ARREST will enroll 860 OHCA patients with ROSC to a randomised clinical trial. Each arm of the trial will include 430 patients.

The two arms are as follows:

Intervention Arm: Direct to CAC The intervention arm consists of activation of the pre-hospital triaging system currently in place for post-arrest STE patients. This involves pre-alert of the CAC and strategic delivery of the patient to the catheter laboratory (24 hours a day, 7 days a week). Patients will receive definitive post-resuscitation care: intubation and ventilation, where necessary, targeted temperature management, and goal directed therapies including evaluation and identification of underlying cause of arrest with access to immediate reperfusion if necessary. Prognostication will occur no earlier than 72 hours post-cardiac arrest to prevent premature withdrawal of life-sustaining treatment. Transfer times estimated from the 40-patient pilot are anticipated to be 100 minutes (median; IQR 75 to 113) from time of arrest to the designated centre.

Control Arm: Standard of Care The control arm comprises the current standard of pre-hospital advanced life support (ALS) care management for patients with ROSC following cardiac arrest of suspected cardiac aetiology. The patient is conveyed to the geographically closest emergency department. Management thereafter will be as per standard hospital protocols however as in the intervention arm, prognostication is to be delayed in trial patients until at least 72 hours post arrest.

Eligibility criteria: Inclusion Criteria:

* Out-of-hospital cardiac arrest (OHCA)
* Return of spontaneous circulation (ROSC)
* Age 18 or over (known or presumed)

Exclusion Criteria:

* Criteria for ST-elevation myocardial infarction on 12-Lead electrocardiogram (ECG)
* Do Not Attempt Resuscitation (DNAR) Order
* Cardiac arrest suffered after care pathway set and patient en route
* Suspected pregnancy
* Presumed non-cardiac cause (for example; trauma, drowning, suicide, drug overdose)
* Presumed significant trauma/injury

Primary outcomes:
measure: All-cause mortality
timeFrame: 30 days after randomisation
Secondary outcomes:
measure: Cerebral performance category score
timeFrame: Discharge (capped at 30 days)
measure: Modified Rankin Score
timeFrame: Discharge (capped at 30 days)
measure: Cerebral performance category score
timeFrame: 3 months after randomisation
measure: Modified Rankin Score
timeFrame: 3 months after randomisation
measure: All-cause mortality
timeFrame: 3 months after randomisation
measure: All-cause mortality
timeFrame: 6 months after randomisation
measure: All-cause mortality
timeFrame: 12 months after randomisation
measure: Patient's quality of life
timeFrame: Discharge (capped at 30 days)
Other outcomes:
Locations:
city: Dartford
country: United Kingdom
facility: Dartford and Gravesham NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: BHR University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Croydon Health Services NHS Trust
city: London
country: United Kingdom
facility: Epsom and St Helier University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS FT
city: London
country: United Kingdom
facility: Hillingdon Hospitals NHS Trust
city: London
country: United Kingdom
facility: Homerton University Hospital NHS Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Kingston Hospital NHS FT
city: London
country: United Kingdom
facility: Lewisham & Greenwich NHS Trust
city: London
country: United Kingdom
facility: London Ambulance Service NHS Trust
city: London
country: United Kingdom
facility: London North West University Healthcare
city: London
country: United Kingdom
facility: North Middlesex University Hospital NHS Trust
city: London
country: United Kingdom
facility: Royal Brompton and Harefield NHS Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Surrey and Sussex Healthcare NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Watford
country: United Kingdom
facility: West Hertfordshire Hospitals NHS Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Simon Redwood, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patterson T, Perkins A, Perkins GD, Clayton T, Evans R, Nguyen H, Wilson K, Whitbread M, Hughes J, Fothergill RT, Nevett J, Mosweu I, McCrone P, Dalby M, Rakhit R, MacCarthy P, Perera D, Nolan JP, Redwood SR. Rationale and design of: A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation out-of-hospital cardiac arrest: The ARREST randomized controlled trial. Am Heart J. 2018 Oct;204:92-101. doi: 10.1016/j.ahj.2018.06.016. Epub 2018 Aug 6.
citation: Patterson T, Perkins GD, Perkins A, Clayton T, Evans R, Dodd M, Robertson S, Wilson K, Mellett-Smith A, Fothergill RT, McCrone P, Dalby M, MacCarthy P, Firoozi S, Malik I, Rakhit R, Jain A, Nolan JP, Redwood SR; ARREST trial collaborators. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. Lancet. 2023 Oct 14;402(10410):1329-1337. doi: 10.1016/S0140-6736(23)01351-X. Epub 2023 Aug 27.