Clinical trial NCT05917717: Cardiac Arrest Bundle of CARE Trial
Official title: Cardiac Arrest Bundle of Care Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiopulmonary Resuscitation
Cardiac Arrest
Out of Hospital Cardiac Arrest
Keywords: Cardiac Arrest
Mechanical CPR
Cardiopulmonary Resuscitation
Impedance threshold device
Active compression decompression CPR
Head up cardiopulmonary resuscitation (HUP-CPR)
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Southampton
name: South Central Ambulance service
name: Hampshire and Isle of Wight air Ambulance
First posted: 2023-06-26
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pilot study - randomised controlled trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Adult patients (\>18 year of age) who have suffered a cardiac arrest
2. Body habitus is compatible with the bundle devices.
3. Witnessed event
4. Time of collapse was known with reasonable certainty to have been to be within 20 minutes.

Exclusion Criteria:

1. Visibly pregnant women
2. Prisoners
3. Traumatic cardiac arrest
4. Drowning
5. Hanging
6. DNACPR
7. Have been in witnessed cardiac arrest for an estimated time of 21 minutes or more

Primary outcomes:
measure: The feasibility of initiating the 'bundle of care' (ability to recruit to the intervention, ability to place the 3 devices in the intervention group and use them as per the protocol.
timeFrame: Through study completion an average of up to 1 year
measure: Feasibility of delivering a single education package on how to use the 'bundle of care'.
timeFrame: 30 days
Secondary outcomes:
measure: First recorded cardiac rhythm of the participants in the trial
timeFrame: 30 Minutes
measure: Signs of life during CPR to include a pulse, an attempt to breathe or to move
timeFrame: 30 minutes
measure: Maximum end tidal carbon dioxide (CO2) during CPR before ROSC.
timeFrame: 30 minutes
measure: Return of spontaneous circulation (ROSC).
timeFrame: 60-120 minutes
measure: Is the participant alive at hospital at the point of handover in the emergency department (i.e. sustained ROSC) or are they dead.
timeFrame: 60-120 minutes
measure: To evaluate any differences between intubation and supraglottic airway use with regard to mortality.
timeFrame: 30 days
measure: To evaluate any differences between intubation and supraglottic airway use with regard to modified Rankin score.
timeFrame: 30 days
measure: Survival to discharge or 30-day survival (whichever is sooner).
timeFrame: 30 days
measure: Survival with a favourable neurological outcome at hospital discharge (or 30 days) using The modified Rankin Scale (mRS)
timeFrame: 30 days
measure: To complete a service user questionnaire on the delivery of the intervention.
timeFrame: 30 days
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation trust
state: England
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: James Plumb, PhD
role: PRINCIPAL_INVESTIGATOR
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