PATIENT ENROLLMENT

What is the protocol each site will follow?

The CIRC study has been designed as a single blinded (blinded only to patients), randomized controlled study, in which randomization will occur at the patient level. Half of patients enrolled will receive conventional manual CPR and the other half mechanical CPR with AutoPulse, both in accordance with American Heart Association and European Resuscitation Council current guidelines, and completely on a randomized basis.

Patients receiving AutoPulse treatment will receive it within 60 seconds of the device's arrival, before which manual CPR will be started. CPR will be interrupted for less than 20 seconds to put the AutoPulse in place. Data is collected for each patient and analyzed so that a comparison between the two treatments can be made.

How is the quality of the study assured?

Prior to the start of the study, each site is reviewed for standard operation procedures, following of the protocol, and other issues. Only sites passing this pre-study phase will be allowed to enroll patients. Everyone involved and who will be using the AutoPulse is extensively trained and certified prior to participation. Periodic testing during the trial will be conducted, assuring quality of AutoPulse use. Collected data is received, stored, and analyzed by independent data monitors. A centralized Data and Safety Monitoring Board, made up of physicians and a statistician, is responsible for monitoring the safety of the trial.

This trial will be conducted in accordance with the principles of Good Clinical Practice (GCP), the applicable Regional Ethics Committee or Institutional Review Board requirements, and relevant informed consent regulations (Declaration of Helsinki). In addition, all local regulatory requirements will be adhered to, in particular those which afford greater protection to the safety of trial patients.

How is patient privacy maintained?

Every effort will be taken to ensure patient confidentiality is maintained at all times. All patient data must be anonymized before retrieval from the trial site. To maintain patient confidentiality, all trial personnel involved in data collection and analysis will be required to sign a confidentiality agreement. In addition, patients will be identified in the database only by a trial number and all links to specific identifiers will be kept at the trial site in a separate secure location. Database files will be maintained on a fire-walled and password-protected computer in a secure location.

What is the informed consent process?

This trial qualifies for a waiver from informed consent requirements for emergency research as outlined in FDA regulation 21 CFR 50.24 and the applicable local national laws of Norway and Austria. The trial would not be feasible without this exception from consent.

The patients enrolled in the CIRC trial will be in cardiac arrest, an immediate life-threatening situation. The standard of care for pre-hospital management of these patients includes the timely provision of CPR. In addition, these patients will be unconscious and unable to provide consent for trial enrollment. Legal next-of-kin will, in all probability, not be immediately available at the scene, nor would it be practical for the pre-hospital provider to explain the trial and receive consent while attempting to care for a patient in cardiac arrest.

Once a trial patient has been admitted to the hospital, every effort will be made to contact legal representatives to notify them that the patient has been enrolled in a randomized trial. If a legal representative is not immediately available, research personnel will attempt to contact the representative as expeditiously as feasible. In those countries with different regulations, the regulations for those countries will be followed. A summary of all such efforts will be documented in the patient's chart. In the event the patient becomes competent during the trial period, then he/she will be approached as soon as feasible by research personnel for notification of enrollment.

How are patients selected for each treatment?

The assignment of a patient to a treatment arm of the trial will be conducted using a pre-determined randomization schedule that has been prepared and dispersed to each site prior to the start of the trial. The randomization schedule will help to avoid possible bias in the allocation of patients.

Upon enrollment each patient will be randomized to Manual-CPR or AutoPulse-CPR in a proportion of 1:1. To facilitate this, an AutoPulse device will be taken to each suspected out-of-hospital cardiac arrest.

Who qualifies to be enrolled in this trial?

Patients aged 18 years (or local age of consent) or more who suffer cardiac arrest in an out-of-hospital setting.

Excluded are:

• Traumatic arrest (blunt, penetrating, burns)
• Arrest due to exsanguinations, strangulation, smoke inhalation, drug overdose, electrocution, hanging, drowning.
• Known or clinically apparent pregnancy
• Do Not Attempt to Resuscitate (DNAR) orders
• Wards of the state
• Prisoners
• Patients who are reached after 16 minutes after the time of emergency call (911).

How many enrollees do you need?

It is estimated that between 3000 and 6000 patients will be enrolled over the 2 to 3 year period for all sites.