Pre-hospital ECMO in Advanced Resuscitation in Patients With Refractory Cardiac Arrest. ( SUB30 ) (SUB30)

Feasibility Study of a Pre-hospital Extra-corporeal Membrane Oxygenation (ECMO) Capable Advanced Resuscitation Team at Achieving Blood Flow Within 30 Minutes in Patients With Refractory Cardiac Arrest.

To establish whether a pre-hospital advanced physician/ paramedic cardiac arrest team that is ECMO capable can establish ECMO flow within 30 minutes of collapse. The Sub30 study will investigate the technical and logistical feasibility of instituting pre-hospital Extracorporeal Cardiopulmonary Resuscitation (ECPR) within 30 minutes of collapse for selected patients (n=6) in a geographical sector of Greater London. It will achieve this through a unique collaboration between the primary emergency dispatch and response services (London Ambulance Service NHS Trust, LAS), pre-hospital practitioners (LAS and London Air Ambulance) and clinicians in ECMO (Barts Health NHS Trust).

Study Overview

• Status: Unknown
• Conditions: Ventricular Fibrillation; Cardiopulmonary Arrest With Successful Resuscitation; Death, Sudden, Cardiac; Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Procedure: ECMO resuscitation

Detailed Description

Every year, in London, the ambulance service treats over 4,000 patients who have a had a cardiac arrest (or their heart has stopped). Less than 1 in 10 patients survive to get home. Some of those who survive have severe brain damage since their brains did not receive blood and oxygen when their heart was stopped. The ambulance service in London manages to get to a patient, on average, 7 minutes following a 999 call. The paramedics are very skilled in restarting people's hearts and often manage this in less than 10 minutes. However, sometimes it can take much longer or not be possible. The risks of a patient dying or suffering brain damage increase the longer it takes to restart the heart, particularly after about 20-30 minutes. An extracorporeal membrane oxygenation (ECMO) machine may reduce these risks by pumping a patient's blood through an artificial lung and to their vital body organs - temporarily replacing the function of the heart and lungs. The ECMO is used in normal care to support patients after a cardiac arrest once a patient reaches the hospital, but in this study we want to see if the ECMO can be used very soon after the cardiac arrest is reported via the 999 call.

In the Sub30 study, the ECMO team and machine to travel immediately to where the patient collapses rather than wait for the patient to be moved to a hospital. The study hypothesis is that the ECMO will be started faster and that this may improve patient survival and outcomes.

The ECMO team consists of three senior doctors and a paramedic. They attend patients who have collapsed and start ECMO if standard advanced resuscitation techniques fail to restart the heart in 20 minutes. The team will aim to have the ECMO machine started within 30 minutes of the 999 call. The team have achieved this in training and the current study will assess whether it is possible to do this in six patients in real-life.

A target of thirty minutes to achieve ECMO flow or return of spontaneous circulation (ROSC) is less than in published series to date. This can be achieved by:

• integration into an established pre-hospital emergency response services that aggressively pursue ROSC through optimised Advanced Life Support
• immediate deployment of an ECPR-capable cardiac arrest team as a primary resource, as opposed to delayed secondary deployment. Dispatch will be done by the established Advanced Paramedic Practitioner (APP) desk of London Ambulance Service, with the objective to reach the patient within 8-10 minutes of the 999 call.
• early placement of guide-wires into the femoral vessels during on-going conventional CPR, a procedure with low complication risk that does not commit the team to ECPR but will minimise the delay to ECPR support if conventional resuscitative techniques are not successful within 20 minutes
• facilitated guide-wire placement through real-time wireless ultrasound delivered to the operator through augmented reality smart glasses.

Some out of hospital cardiac arrests (OHCA) are irreversible in nature and ECPR would not provide benefit to these patients. The ECPR team will not be task fixated on providing ECPR, but also supportive of the APP primary responders and provide ECPR only in settings of refractory cardiac arrest that fulfils the study criteria, that have been chosen based on best available evidence to identify those patients in whom ECPR is likely to be of benefit.

If pre-hospital ECMO is feasible within 30 minutes of chest compressions starting, then a larger randomised controlled study of clinical and cost effectiveness is merited. Optimisation of the delivery of ECPR is vital, prior to a controlled study, in order to maximise any potential benefits for patients.

Data from Sub30 will inform the design of such studies enabling an estimation of the size of any potential outcome benefits and the likely affordability for a healthcare service.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1 6BQ
    • St Bartholomew'S Hospital
  • London, United Kingdom, SE1 0BW
    • London Ambulance Service Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult patients who:

• have a witnessed out-of-hospital cardiac arrest
• a presumed cardiac aetiology to their cardiac arrest
• receive bystander chest compressions within 3 minutes
• remain in cardiac arrest at 20 minutes following the call to the emergency services or fail to sustain ROSC in the pre-hospital setting

Exclusion Criteria:

The following patients will not be suitable for entry into the study:

• Known to be are visibly appear younger than 18 years old or older than 65 years.
• Known or visible advanced pregnancy (when resuscitative hysterotomy should be performed)
• No signs of life (physical movement or breathing) AND evidence of ineffective chest compressions suggested by:
• absence of electrical activity at 20 minutes time out OR
• end tidal carbon dioxide level of less than 1.3 kPa (10 mmHg)
• Evidence from others present at the scene or patient examination that ECMO unlikely to benefit patient (e.g. advanced malignancy, severe frailty).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ECMO resuscitation; 6 patients who meet the eligibility criteria will be treated by pre-hospital advanced physician/ paramedic cardiac arrest team that is ECMO capable and can establish ECMO flow within 30 minutes of collapse	Procedure: ECMO resuscitation; Extracorporeal Cardio-Pulmonary Resuscitation (ECPR) using ECMO within 30 minutes of cardiac arrest; Other Names: Extracorporeal Membrane Oxygenation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients successfully established with pre-hospital ECPR	The primary endpoint is the proportion of patients successfully established with pre-hospital ECPR within 30 minutes of collapse	Within 30 minutes of collapse

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulance dispatch	Number of patients not dispatched to as travel time too great/team unavailable	Within 30 minutes of collapse
Successful cannulation	The number of patients successfully cannulated 31 and 45 minutes	between 31 and 45 minutes; and 46 and 60 minutes.
Number of patients with return of spontaneous circulations (ROSC)	The number of patients patients who achieve ROSC prior to the 20 minutes timeout, number of patients in refractory cardiac arrest at 20 minutes in whom ROSC is achieved prior to ECMO flow	Within 20 minutes of cardiac arrest
Emergency call-out time frame	The time interval between call to the emergency services and ECPR team arrival	At 30 minutes after cardiac arrest
Successful guide wire placement	The proportion of potentially supportable patients in whom guidewire placement is attempted and achieved	Up to 30 minutes after cardiac arrest
Incidence of ECPR-related complications	Assessment of ECPR-related complications, such as incidence of vascular damage, haemorrhage requiring transfusion and new organ dysfunction	Duration of ECMO run, between 3 - 14 days
Clinical outcome via FIM at 3 months	Assessment of functional status at hospital discharge using the Functional Independence Measure - FIM (18 item scale, measure of dependence. The higher the score, the more independent the patient is in performing the task).	3 months
Clinical outcome via MRS at 3 months	Assessment of functional status at hospital discharge using the modified Rankin Scale (MRS) (scale 0-6, measuring the degree of disability or dependence in the daily activities, where 0 is no symptoms and 6 is dead)	3 months
Duration of hospital stay	Assessment of health resources used for the duration of Intensive Care Unit stay	1-3 months
Number of acute hospital admissions post discharge	Assessment of health resources used for further hospital admissions following discharge.	3 months

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Collaborators: Stryker Nordic; London's Air Ambulance; Bodychillz Ltd; Maquet Cardiopulmonary GmbH
• Investigators: Principal Investigator: Simon Finney, Barts & The London NHS Trust

Publications and helpful links

General Publications

• Singer B, Reynolds JC, Davies GE, Wrigley F, Whitbread M, Faulkner M, O'Brien B, Proudfoot AG, Mathur A, Evens T, Field J, Monk V, Finney SJ; International ECMO Network (ECMONet). Sub30: Protocol for the Sub30 feasibility study of a pre-hospital Extracorporeal membrane oxygenation (ECMO) capable advanced resuscitation team at achieving blood flow within 30 min in patients with refractory out-of-hospital cardiac arrest. Resusc Plus. 2020 Dec;4:100029. doi: 10.1016/j.resplu.2020.100029. Epub 2020 Oct 8.

Helpful Links

• Bart Cardiovascular Clinical Trials Unit (CVCTU) portfolio - SUB30 study

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Advanced life support (ALS); Extra-corporeal Membrane Oxygenation Resuscitation (ECMO)
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Death; Heart Arrest; Ventricular Fibrillation; Out-of-Hospital Cardiac Arrest; Death, Sudden, Cardiac; Death, Sudden
• Other Study ID Numbers: 012543; 244748 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to share study participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No