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, or even superior to standard CPR in situations where the bystander has previous CPR training remains unclear. This clinical question remains unanswered while millions of people are trained in CPR worldwide each year.

To investigate whether CO-CPR is non-inferior to standard CPR (S-CPR) when performed by a bystander with previous CPR training in witnessed, non-asphyxic cases of OHCA. Superiority testing will also be performed for the purpose of demonstrating a possible increase in survival with CO-CPR.

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 rate of bystander-CPR by itself, a non-inferiority design for the primary outcome has been chosen. Superiority testing will also be performed to demonstrate a potential 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 include 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.

This is a national study where all dispatch centers in Sweden participate, and since 2025, selected sites in northern Italy.

The overall study project is conducted in three different phases:

1. RUN-IN period, for establishing logistical and technical study procedures (completed)
2. PILOT STUDY, with focus on feasibility, logistics, and safety (completed)
3. MAIN STUDY will focus on 30-day survival (primary end point) and other important clinical outcomes (secondary outcomes)

Objective for 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 PILOT study aimed to assess the 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 the last patient was 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 MAIN study aims to evaluate whether survival to 30 days following instructions to perform CO-CPR is non-inferior to instructions to perform S-CPR in witnessed OHCA where the bystander has previous CPR training.

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 below 18 years
• Collapse is not witnessed
• Bystander has no prior CPR training
• Obvious asphyxia (i.e. hanging, foreign body, suffocation, strangulation)
• Obvious drug overdose / intoxication
• Pregnancy
• Trauma (penetrating, blunt, burn injury)

Post randomisation exclusion Criteria from data analysis:

• Not EMS-verified cardiac arrest
• Previous do not resuscitate (DNR) decision

Data will be published on group level only

Because of the inherent logistical problems, where the dispatcher at the emergency medical dispatch center can not be blinded to the randomized allocation (instruction), the study is defined as open-label.

Treatment allocation will, however, be blinded for EMS, data management, and at follow-up, for clinicians treating the patients at the hospitals, and for all responsible researchers. Allocation concealment will be preserved.