An out-of-hospital cardiac arrest is a sudden event where the heart stops beating and a
person becomes unresponsive. During this event, vital organs in the body receive no blood
flow, causing them to shut down. Without intervention to restart the heart, a person
effectively dies. In the UK, around 60,000 people experience cardiac arrests each year,
with most occurring at home. Despite prompt emergency service response, survival rates
are typically low.

There is technology available that has the potential to improve survival rates for
out-of-hospital cardiac arrests. The intervention involves three devices used together:
head-up position CPR (Elegard), active compression-decompression mechanical CPR
(Lucas-3), and the Impedance Threshold device (Resqpod-16). When combined, these devices
can enhance blood flow during resuscitation, potentially leading to improved initial
resuscitation rates and higher rates of survival with normal brain function after a
cardiac arrest.

A pilot study is planned to test the feasibility of using these devices. The results will
inform the design of a larger study to determine if this technology can indeed improve
survival rates in out-of-hospital cardiac arrests.

Cardiac Arrest Bundle of cARE Trial

Cardiopulmonary Resuscitation

Cardiac Arrest

Out of Hospital Cardiac Arrest

Out of hospital cardiac arrest (OOHCA) is the sudden cessation of effective
cardiovascular circulation in the pre hospital setting. This is sadly a common occurrence
within the UK with approximately 60,000 OOHCAs per year. In 30,000 of these,
resuscitation is attempted by the ambulance service. Survival remains poor (2-12%) within
the UK and even the best performing regions still lag someway behind exemplar global
systems (Seattle 21%, Norway 25%). There are a plethora of reasons for variation in
outcome, not limited to the availability of community defibrillators, the education and
ability of bystanders to provide effective CPR, the response times of the emergency
medical personnel, the training of emergency services personnel and their individual
exposure to cardiac arrest, the availability of primary percutaneous coronary
intervention, and even the availability of extracorporeal resuscitation.

Despite poor outcomes from OOHCA for decades, there exists promising data from animal and
cadaver studies that new technological devices could improve the currently poor blood
flow generated by chest compressions during CPR, particularly cerebral blood flow. The
current standard of care for patients with an OOHCA includes manual CPR delivered at a
rate of 100-120 compressions per minute with a depth of 5 cm (maximum 6 cm). In turn,
periodic inflation of the lungs using positive pressure ventilation to maintain
oxygenation is mandated during CPR. Animal data have shown that blood flow to the heart
and brain using this method is approximately 15-30% of normal. Conventional CPR is
therefore unphysiological by definition, with intracerebral pressures being too high in
the compression phase and intrathoracic pressure being too high in the release phase for
adequate blood flow to the brain and heart respectively. Mechanisms and tools to improve
this have been available for some time but using them synergistically to achieve improved
cerebral and coronary blood flow is a relatively recent advance.

It is now possible to mimic a more physiologically normal situation by combining 3 pieces
of technology. These may lead to better organ perfusion during CPR and therefore better
rates of survival. The 3 devices in question do this in different complementary ways, in
turn;

  1. Head up position- gradated elevation of the head after CPR has been initiated,
     improves cerebral blood flow during CPR. This has been studied predominantly in
     porcine models. HUP-CPR enhances venous return, and reduces intracranial pressure
     during the decompression phase of CPR. This results in improved cerebral perfusion
     pressure and improves cerebral blood flow.

  2. Active compression/decompression CPR uses a device with a suction cup placed on the
     thorax that via active decompression generates a negative intrathoracic pressure on
     each upward stroke, meaning that venous return to the heart improves during each
     cycle of CPR, allowing more blood to then be pumped to the brain on the next
     compressive cycle.

  3. Combined with an impedance threshold device which works by limiting air entry into
     the lungs during chest recoil between chest compressions thereby enhancing the lower
     intrathoracic pressure achieved by active decompression, as described above.

The first retrospective study examining the combination of active compression
decompression CPR with an ITD and HUP-CPR in humans was published in 2022, concluding
that rapid initiation of bundle of care-CPR was associated with a higher likelihood of
survival to hospital discharge after OHCA when compared with conventional CPR. 9. The
first prospective human study using this triple bundle approach is currently ongoing in
France.

The 3 devices described above are all CE marked meaning that this trial is not a trial of
an experimental device and therefore does not need to be reported to the MHRA for their
regulatory approvals.

Justification for undertaking the trial

Survival from OOHCA in the UK remains extremely poor (2-12%). The fact that this has not
changed over many decades is of concern. Additionally, the global health disparity that
exists in survival from OOCHA between different healthcare systems is stark.

The published animal data has created a plausible biological signal that improvements
with cerebral blood flow are indeed possible using a bundle approach to neuroprotective
CPR. The practicalities of performing this in human subjects in cardiac arrest is already
being done in certain emergency medical systems globally. One study has published
retrospective data with a signal to suggest that improved outcomes are possible using
this approach. As far as the investigators are aware, no randomised control trial is
currently being undertaken to test this hypothesis.

The proposed treatment bundle holds the potential to change this, the investigators are
of the opinion that this should be tested scientifically within the remit of a clinical
trial and this is the first necessary stage of that process. The individual components
have shown promise in animal studies but this has not been borne out in the human trials
that have followed. The synergistic and complementary effect of the 3 devices that make
up the bundle of care in this study have the potential to change outcomes.

In parts of the USA (Seattle and Phoenix Fire departments) this bundle of care has been
brought in due to the marked improvements in survival that have been seen. The
investigators are of the opinion that an adequately powered randomised trial is essential
to confirm these possible benefits.

Research statement

Out-of-hospital cardiac arrest (OOHCA) is a common event with poor long-term survival
rates, often resulting in poor neurological outcomes. While there are several
interventions that may improve survival and neurological outcomes, single interventions
alone have not consistently demonstrated significant improvements in outcomes. The
combination of head up cardiopulmonary resuscitation (CPR), active compression
decompression CPR, and the use of an impedance threshold device has not yet been tested
in a pragmatic randomised controlled trial. Therefore, the objective of this study is to
assess the feasibility of conducting a randomized trial comparing usual care with a
"bundle of care" approach incorporating the above interventions to improve patient
outcomes after OOHCA.

Neuroprotective 'bundle of care'

Cardiac Arrest Bundle of Care Trial

The feasibility of initiating the 'bundle of care' (ability to recruit to the
intervention) and to adequately perform the randomisation and crossover of each arm
within each participating service, evidenced by the number of eligible patients and the
number recruited.

The feasibility of delivering an education package to teach the procedure for the bundle
of care intervention and the success of said education package, evidenced by the number
of staff trained and the incidence of non-compliance. The package will contain classroom
teaching and video resources.

To record the initial cardiac arrest rhythm, asystole, pulseless electrical activity,
ventricular fibrillation or ventricular tachycardia.

Signs of life during CPR- Presence of agonal respirations and other signs of life
(pupillary response, movement during CPR)

To mark the time of ROSC is it is achieved.

Is the patient alive or dead, this is a binary outcome measure

The Modified Rankin score is a score from 0-5 with a higher score indicating a worse
neurological outcome after cardiac arrest. The values are as follows.

0 The patient has no residual symptoms.

  1. The patient has no significant disability; able to carry out all pre-stroke
     activities.

  2. The patient has slight disability; unable to carry out all pre-stroke activities but
     able to look after self without daily help.

  3. The patient has moderate disability; requiring some external help but able to walk
     without the assistance of another individual.

  4. The patient has moderately severe disability; unable to walk or attend to bodily
     functions without assistance of another individual.

  5. The patient has severe disability; bedridden, incontinent, requires continuous care.

To evaluate the opinions of the paramedics and doctors recruiting to the trial regarding
the use of the equipment in the intervention group and any barriers to recruitment.

Usual care for a cardiac arrest patient with no deviation.

The clinical team will follow a specific sequence of actions using three devices
(Elegard, Lucas-3, and ITD-16), in addition to standard CPR. Firstly, they will place the
ITD onto the i-gel) or ETT, followed by the Elegard device and the LUCAS-3. The team will
also place a cerebral saturation monitor on (Near-Infrared Spectroscopy (NIRS)) (if they
have access to one). After 2 minutes of CPR via the LUCAS-3 with the ResQPOD-16 (ITD),
the Elegard device will be turned on and activated to gradually elevate the head
approximately 22cm from the ground to the back of the occiput. If necessary, the clinical
team may choose to intubate the trachea at this point. Resuscitation will continue for at
least 30 minutes or until ROSC is achieved. If ROSC is achieved, standard post ROSC
guidelines will be followed.

Cardiac Arrest Bundle of cARE Trial

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status