Clinical trial NCT03981107: Compression Only CPR Versus Standard CPR in Out-Of-Hospital Cardiac Arrest - A Randomized Survival Study
Official title: A Randomized Trial Comparing Survival After of a Simplified Form of Cardiopulmonary Resuscitation (CPR) Consisting of Compressions Only Compared to CPR With Compressions and Rescue Breaths
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Out-Of-Hospital Cardiac Arrest
Cardiac Arrest
Cardiopulmonary Resuscitation
Keywords: Cardiopulmonary Resuscitation
Chest compressions only CPR
Dispatcher assisted CPR
Cardiac Arrest
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Swedish Heart Lung Foundation
name: The Swedish Research Council
name: SOS Alarm
name: Azienda Regionale Emergenza Urgenza - AREU Lombardia
First posted: 2019-06-10
Enrollment: 3260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, 1:1, open label, multicenter trial
Primary purpose: TREATMENT

Brief summary: Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of mortality in the industrialized world. Bystander CPR before arrival of the Emergency Medical Service (EMS) is associated with an increased chance of survival. During the last decade, the best form of bystander CPR has been debated. Chest Compression Only CPR (CO-CPR) has been advocated as a preferable method in situations where the bystander has no previous knowledge in CPR, both because its believed to be equally efficient but also a simplified form of CPR that could lead to a higher incidence of bystander-CPR.

In an initiative to increase CPR rates the American Heart Association has launched public campaigns such as the "hands-only CPR" promoting CO-CPR as an option to S-CPR for adult non-asphyxic cardiac arrest. In the 2015 updates of the European resuscitation council guidelines it states that the confidence in the equivalence between the two methods is not sufficient to change current practice.

Whether CO-CPR leads to a survival rate no worse than, equally effective, or even superior to standard CPR in situations where the bystander has previous CPR training however remains unclear. This clinical question remains unanswered while millions of people are trained in CPR worldwide each year.

The overall purpose with this research project is to investigate whether instructions to perform a simplified form of CPR consisting of compressions only (CO-CPR) to bystanders with prior CPR-training is non-inferior, or better than, standard CPR (S- CPR) in witnessed Out-of-Hospital Cardiac Arrest (OHCA).

Detailed description: This is an interventional, prospective, randomized, 1:1 open label, multicenter trial comparing two different methods of bystander CPR in witnessed cases of OHCA. Since CO-CPR is a simplified form of CPR that could lead to a higher incidence of bystander-CPR by itself a non-inferiority design for the primary outcome has been chosen. Superiority testing will also be performed for the purpose of demonstrating a possible increase in survival with CO-CPR.

Witnessed cases of OHCA with a non-asphyctic aetiology will be the principal study population. According to current guidelines an unresponsive patient with no or agonal breathing is treated as a suspected case of OHCA at the dispatch centre. These cases are eligible for screening for inclusion. If the case is witnessed, the bystander has previous knowledge in CPR and no exclusion criteria are present, the case can be included in the study. If included, it will be randomly assigned to either CO-CPR (intervention) or S-CPR (control).

The intervention consists of instructions from a dispatcher at the dispatch center to bystanders to perform either CO-CPR (intervention) or S-CPR (control).

* Instructions to bystanders on how to perform CO-CPR includes continuous chest compressions without interruptions or rescue breaths.
* Instructions to bystanders on how to perform S-CPR in the control group include information on giving chest compressions and rescue breaths in a 30:2 ratio (like current CPR recommendation state).

This is a national study were all dispatch centers in Sweden participate.

The overall study project is conducted in three different phases:

1. Pre study RUN-IN period, for establishing logistical and technical study procedures (completed)
2. PILOT STUDY, with focus feasibility, logistics and safety (Active, not recruiting)
3. MAIN STUDY will focus on 30 days survival (primary end point) and other important clinical outcomes (secondary outcomes)

Objective pre study RUN-IN period:

In order to test the technical inclusion procedures, logistics, feasibility and data collection a pre-study RUN-IN period started in Stockholm during 2015.

Objective PILOT study:

The aim of the PILOT study is to assess safety and feasibility of the TANGO2 trial design, as well as intermediate clinical outcomes. The TANGO2 trial started recruitment of patients on January 1st 2017 and last patient included on December 31st 2018. All patients from the PILOT study will be included in the MAIN STUDY in a seamless design.

Objective MAIN study:

The aim of the MAIN study is to evaluate whether survival to 30 days following instructions to perform CO-CPR is non-inferior compared to instructions to perform S-CPR bystanders in witnessed OHCA where the bystander has previous CPR training. Secondary and exploratory objectives include the evaluation of neurological favorable survival, return of spontaneous circulation, admission to hospital, long-term survival and other clinical outcome variables as well as evaluations of 30-day survival between CO-CPR and S-CPR in pre-specified subgroups. The MAIN study will include patients from the PILOT phase in a seamless design

Experiences from the pre study RUN-IN period and implications for the PILOT and MAIN studies:

The pre-study RUN-IN period started in Stockholm County in 2015 and analysis were performed during 2016. After continuous technological adjustments, the randomization module was integrated within the computer aided dispatch system and was found to functioned well in the end of 2016. However, during pre-study RUN-IN period, one major obstacle was identified. Due to unexpected technological matters and an unanticipated new organization of the dispatch centers in Sweden only about 15% of the cardiac arrest calls for patients suffering cardiac arrest in Stockholm were actually answered by dispatchers in Stockholm; all other calls were transferred to other dispatch centers throughout Sweden. This meant that the dispatchers had to consider the geographical site of the suspected cardiac arrest and remember if that area was part of the study area. This new organization and logistics, were the call could be made in one area and answered and handled at another site and county during the pre-study RUN-IN period, resulted in a far greatly slower inclusion rate than anticipated and made a correct follow-up of patients unmanageable and unreliable. This made it impossible to conduct a PILOT study in Stockholm only.

As a consequence, a decision was made by the steering committee:

A) To move the start of the PILOT study forward, until completion of the national expansion of the study and not to start inclusion of patients into the PILOT study before January 1st 2017. The new length of the PILOT study was set to two years to assure sufficient inclusion of patients to assess safety in terms of survival to hospital admission.

B) That the PILOT study seamlessly will move on into the MAIN study in an inferentially seamless manner after the PILOT phase inclusion ended on Dec 31 2018. This means that patients from the PILOT study will also be included in the MAIN survival study. The outcomes for the PILOT study were changed to not interfere with the primary endpoint of the main survival study (see below). Inclusion and Exclusion criteria remained unchanged throughout the TANGO2-project.

Eligibility criteria: Inclusion Criteria:

* Unconsciousness with no, abnormal or agonal breathing (suspected OHCA)
* The suspected OHCA is witnessed (seen or heard)
* Any Bystander at the scene has previous training in CPR

Exclusion Criteria:

* Age 18 or younger
* Collapse is not witnessed
* Bystander has never been taught CPR. (These bystanders should be instructed to administer CO-CPR in accordance to guidelines)
* Asphyxia, i.e. drowning, strangulation, hanging
* Intoxication or drug overdose
* Pregnancy
* Trauma

Post randomisation exclusion Criteria from data analysis:

* Previous decision that CPR should not be initiated i.e. terminal illness or palliative care
* No Cardiac arrest, other condition (Cases where EMS did not start CPR)

Primary outcomes:
measure: 30-day survival
timeFrame: 1 month
Secondary outcomes:
measure: Survival to hospital admission
timeFrame: 1 day
measure: One year survival
timeFrame: 1 year
measure: Survival with good neurologic outcome at discharge
timeFrame: 30 days
measure: Survival with complete neurologically outcome
timeFrame: 30 days
Other outcomes:
measure: Proportion of participants found with VT/VF at first rhythm analysis
timeFrame: 1 day
measure: Proportion of participants with return of spontaneous Circulation (ROSC)
timeFrame: 1 day
measure: Analysis of primary endpoint (30-day survival) in pre-defined subgroup
timeFrame: 30 days
Locations:
city: Bergamo
country: Italy
facility: AREU, Agenzia Regionale Emergenza Urgenza
city: Stockholm
country: Sweden
facility: SOS Alarm AB
Study officials:
affiliation: Karolinska Institutet, Department of Medicine Solna
name: Jacob Hollenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Milan
name: Giuseppe Ristagno, MD, PhD
role: STUDY_CHAIR
References: