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Cardiac Arrest Bundle of cARE Trial (CABARET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05917717
Recruitment Status : Not yet recruiting
First Posted : June 26, 2023
Last Update Posted : March 29, 2024
Sponsor:
Collaborators:
University of Southampton
South Central Ambulance service
Hampshire and Isle of Wight air Ambulance
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE May 25, 2023
First Posted Date  ICMJE June 26, 2023
Last Update Posted Date March 29, 2024
Estimated Study Start Date  ICMJE April 2024
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2023)
  • 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. [ Time Frame: Through study completion an average of up to 1 year ]
    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.
  • Feasibility of delivering a single education package on how to use the 'bundle of care'. [ Time Frame: 30 days ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2024)
  • First recorded cardiac rhythm of the participants in the trial [ Time Frame: 30 Minutes ]
    To record the initial cardiac arrest rhythm, asystole, pulseless electrical activity, ventricular fibrillation or ventricular tachycardia.
  • Signs of life during CPR to include a pulse, an attempt to breathe or to move [ Time Frame: 30 minutes ]
    Signs of life during CPR- Presence of agonal respirations and other signs of life (pupillary response, movement during CPR)
  • Maximum end tidal carbon dioxide (CO2) during CPR before ROSC. [ Time Frame: 30 minutes ]
  • Return of spontaneous circulation (ROSC). [ Time Frame: 60-120 minutes ]
    To mark the time of ROSC is it is achieved.
  • Is the participant alive at hospital at the point of handover in the emergency department (i.e. sustained ROSC) or are they dead. [ Time Frame: 60-120 minutes ]
    Is the patient alive or dead, this is a binary outcome measure
  • To evaluate any differences between intubation and supraglottic airway use with regard to mortality. [ Time Frame: 30 days ]
  • To evaluate any differences between intubation and supraglottic airway use with regard to modified Rankin score. [ Time Frame: 30 days ]
    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.
  • Survival to discharge or 30-day survival (whichever is sooner). [ Time Frame: 30 days ]
  • Survival with a favourable neurological outcome at hospital discharge (or 30 days) using The modified Rankin Scale (mRS) [ Time Frame: 30 days ]
    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 complete a service user questionnaire on the delivery of the intervention. [ Time Frame: 30 days ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2023)
  • First recorded cardiac rhythm of the participants in the trial [ Time Frame: 30 Minutes ]
    To record the initial cardiac arrest rhythm, asystole, pulseless electrical activity, ventricular fibrillation or ventricular tachycardia.
  • Signs of life during CPR to include a pulse, an attempt to breathe or to move [ Time Frame: 30 minutes ]
    Signs of life during CPR- Presence of agonal respirations and other signs of life (pupillary response, movement during CPR)
  • Cerebral oxygenation during CPR. [ Time Frame: 30 minutes ]
    (where the monitor is available) using near-infrared spectroscopy (NIRS)
  • Maximum end tidal carbon dioxide (CO2) during CPR before ROSC. [ Time Frame: 30 minutes ]
  • Return of spontaneous circulation (ROSC). [ Time Frame: 60-120 minutes ]
    To mark the time of ROSC is it is achieved.
  • Is the participant alive at hospital at the point of handover in the emergency department (i.e. sustained ROSC) or are they dead. [ Time Frame: 60-120 minutes ]
    Is the patient alive or dead, this is a binary outcome measure
  • To evaluate any differences between intubation and supraglottic airway use with regard to mortality. [ Time Frame: 30 days ]
  • To evaluate any differences between intubation and supraglottic airway use with regard to modified Rankin score. [ Time Frame: 30 days ]
  • Survival to discharge or 30-day survival (whichever is sooner). [ Time Frame: 30 days ]
  • Survival with a favourable neurological outcome at hospital discharge (or 30 days) using The modified Rankin Scale (mRS) [ Time Frame: 30 days ]
  • To complete a service user questionnaire on the delivery of the intervention. [ Time Frame: 30 days ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiac Arrest Bundle of cARE Trial
Official Title  ICMJE Cardiac Arrest Bundle of Care Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Pilot study - randomised controlled trial
Masking: Single (Outcomes Assessor)
Masking Description:

The study team will not be blinded to which patients receive which arm of the trial and will be aware of what each service is delivering in each phase of the study. The research team carrying out the flow up will be blinded to the arm of the trial that the participant was in when they are collecting outcome and follow up data.

It is impossible to blind the care providers.

Participants will be blinded to which arm of the trial they were in (should they regain capacity).

Primary Purpose: Treatment
Condition  ICMJE
  • Cardiopulmonary Resuscitation
  • Cardiac Arrest
  • Out of Hospital Cardiac Arrest
Intervention  ICMJE Procedure: Neuroprotective 'bundle of care'

This includes the 3 devices:

  • Head up cardiopulmonary resuscitation (HUP-CPR)
  • Active compression decompression CPR
  • Impedance threshold device (ITD)
Study Arms  ICMJE
  • No Intervention: Control (usual care)
    Usual care for a cardiac arrest patient with no deviation.
  • Experimental: Intervention 'bundle of care'
    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.
    Intervention: Procedure: Neuroprotective 'bundle of care'
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 22, 2024)
32
Original Estimated Enrollment  ICMJE
 (submitted: June 14, 2023)
30
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: James OM Plumb, PhD 07967319438 j.plumb@soton.ac.uk
Contact: Martina Brown martina.brown@scas.nhs.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05917717
Other Study ID Numbers  ICMJE CABARET
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: We will use this data to inform a definitive trial in this area
Current Responsible Party University Hospital Southampton NHS Foundation Trust
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital Southampton NHS Foundation Trust
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • University of Southampton
  • South Central Ambulance service
  • Hampshire and Isle of Wight air Ambulance
Investigators  ICMJE
Principal Investigator: James Plumb, PhD University Hospital Southampton NHS Foundation Trust
PRS Account University Hospital Southampton NHS Foundation Trust
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP