A Randomized Controlled Trial on Early Double External Sequential Defibrillation in Out of Hospital Cardiac Arrest
Phase: NA
Conditions: Cardiac Arrest, Out-Of-Hospital Cardiac Arrest, Ventricular Fibrillation
Sponsor: St. Olavs Hospital

                       
 
 
The Dual Defib Trial 
A randomised trial on early double external sequential 
defibrillation in out-of-hospital cardiac arrest 
 
 
 
 
 
Sponsor  
Clinic of cardiology, St. Olavs University Hospital 
 
Funder  
Norwegian Air Ambulance Foundation 
 
 
 
 
 
Chief investigator  
Dr Jostein Rødseth Brede, MD, PhD  
 
 
Other investigators 
 
 
 Dr Vegard Nordviste, MD 
Prof Andreas Jørstad Krüger, MD, PhD 
Prof Marius Rehn, MD, PhD 
 
 
 
 
 
 
 
 
Protocol version 2.0 Date 12.06.2024 
 
 

                       
1. Contact details   
 
Sponsor 
 
Name   
 
Clinic of Cardiology, St. Olavs University Hospital  
Contact person   
Rune Wiseth, Head of Clinic 
Address 
 
Postboks 3250 Torgarden, 7006 Trondheim, Norway 
E-mail address  
post.hjertemedisin@stolav.no  
 
Chief Investigator  
Name   
 
Jostein Rødseth Brede  
Professional position  MD, PhD, Consultant Anaesthesiologist   
Address 
 
Luftambulansen Trondheim, Vestre Rosten 114, 7075 Trondheim, Norway.  
E-mail address  
Jostein.brede@norskluftambulanse.no 
Phone number  
+47 994 45 914 
 
PhD candidate  
Name   
 
Vegard Nordviste   
Professional position  MD  
Address 
 
Luftambulansen Trondheim, Vestre Rosten 114, 7075 Trondheim, Norway.  
E-mail address  
Vegard.nordviste@norskluftambulanse.no  
Phone number  
+47 90777686 
 
Main funder 
Name   
 
Norwegian Air Ambulance Foundation  
Contact person   
Tom Hanssen, Director of Research and Development    
E-mail address  
tom.hanssen@norskluftambulanse.no  
 
 

                       
2. Project management  
 
Jostein Rødseth Brede, MD, PhD  
1 Department of Emergency Medicine and Pre-hospital 
Services, St. Olavs University Hospital, Trondheim, Norway  
2 Department of Anaesthesiology and Intensive care, St. Olavs 
University Hospital, Trondheim, Norway  
3 Department of Research, Norwegian Air Ambulance 
Foundation, Oslo, Norway  
   
Vegard Nordviste, MD  
 
3 Department of Research, Norwegian Air Ambulance 
Foundation, Oslo, Norway  
 
Andreas Jørstad Krüger, MD, PhD  
 
1 Department of Emergency Medicine and Pre-hospital 
Services, St. Olavs University Hospital, Trondheim, Norway  
3 Department of Research, Norwegian Air Ambulance 
Foundation, Oslo, Norway  
4 Department of Circulation and Medical Imaging, Faculty of 
Medicine and Health Sciences, Norwegian University of 
Science and Technology (NTNU), Trondheim, Norway  
 
Marius Rehn, MD, PhD  
 
3 Department of Research, Norwegian Air Ambulance 
Foundation, Oslo, Norway  
5 Air Ambulance Department, Division of Prehospital 
Services, Oslo University Hospital, Oslo, Norway 
6 Institute of Clinical Medicine, University of Oslo, Oslo, 
Norway 
 
Jostein Dale, MD  
 
1 Department of Emergency Medicine and Pre-hospital 
Services, St. Olavs University Hospital, Trondheim, Norway  
 
 

                       
3. Table of contents  
Innhold 
1. 
Contact details ......................................................................................... 2 
2. 
Project management ................................................................................. 3 
3. 
Table of contents ....................................................................................... 4 
4. 
Abbreviations ............................................................................................ 6 
5. 
Background ............................................................................................... 7 
Potential eligible patients ..................................................................................................................... 8 
Study rationale .................................................................................................................................... 9 
Academic study ................................................................................................................................... 9 
6. 
Objectives and endpoints .......................................................................... 9 
Primary objective ................................................................................................................................. 9 
Secondary objective ............................................................................................................................ 9 
Primary endpoint ............................................................................................................................... 10 
Secondary endpoints ......................................................................................................................... 10 
Exploratory endpoints ........................................................................................................................ 10 
7. 
Study population ...................................................................................... 10 
Selection of participants .................................................................................................................... 10 
Inclusion criteria ................................................................................................................................ 10 
Exclusion criteria ............................................................................................................................... 11 
Criteria for withdrawal or discontinuation ............................................................................................ 11 
Enrolment ......................................................................................................................................... 11 
8. 
Informed consent process ........................................................................ 11 
9. 
Statistics ................................................................................................. 12 
Statistical hypothesis ......................................................................................................................... 12 
Sample size ....................................................................................................................................... 13 
Interim analyses ................................................................................................................................ 13 
Measures to minimize bias ................................................................................................................. 13 
Selection bias................................................................................................................................ 13 
Performance bias .......................................................................................................................... 13 
Exclusion bias ............................................................................................................................... 13 
Statistical design ............................................................................................................................... 14 

                       
The level of signiﬁcance and power of the clinical study ....................................................................... 14 
Expected drop out rates ..................................................................................................................... 14 
Speciﬁcation of exploratory subgroups ................................................................................................ 14 
Treatment of missing data .................................................................................................................. 14 
Min/max number of subjects per centre .............................................................................................. 14 
10. 
Project methodology and overall design .................................................... 15 
Expected study duration ..................................................................................................................... 15 
Part I ............................................................................................................................................. 15 
Part II ............................................................................................................................................ 16 
Randomisation procedure .................................................................................................................. 16 
Medical devices in the study ............................................................................................................... 16 
11. 
Study procedures ..................................................................................... 16 
Education and training of personnel .................................................................................................... 17 
Outline of the DSED procedure ........................................................................................................... 17 
Follow-up .......................................................................................................................................... 17 
Follow-up medical care ...................................................................................................................... 18 
Discontinuation of the study ............................................................................................................... 18 
Laboratory test .................................................................................................................................. 18 
12. 
Data collection and handling .................................................................... 18 
Data handling .................................................................................................................................... 18 
Source data ....................................................................................................................................... 18 
Storage of study documentation ......................................................................................................... 19 
Data collection .................................................................................................................................. 19 
Data review and editing ...................................................................................................................... 20 
13. 
Study management .................................................................................. 20 
14. 
Study amendments .................................................................................. 20 
15. 
Ethics Committee Approval ...................................................................... 21 
16. 
Other Regulatory Approvals ...................................................................... 21 
17. 
Trial insurance .......................................................................................... 21 
18. 
Trial organisation ...................................................................................... 21 
Organisation ...................................................................................................................................... 21 
The project management .................................................................................................................... 22 
19. 
Data monitoring committee ...................................................................... 22 

                       
20. 
Funding .................................................................................................... 22 
21. 
Conﬂict of Interest ................................................................................... 22 
22. 
Publication policy ..................................................................................... 22 
23. 
References .............................................................................................. 23 
 
 
 
4. Abbreviations  
 
ACLS   
Advanced Cardiovascular Life Support 
CPR  
 
Cardiopulmonary resuscitation  
CRF  
 
Case Report Form 
DSED  
Double Sequential External Defibrillation  
mRS   
Modified Rankin Scale  
OHCA   
Out of Hospital Cardiac Arrest  
REC   
Regional Ethics Committee 
ROSC   
Return of Spontaneous Circulation  
SPIRIT  
Standard Protocol Items: Recommendations for Interventional Trials 
VF  
 
Ventricular fibrillation  
VT  
 
Ventricular tachycardia 
 
 
 
 
 

                       
5. Background   
 
Out-of-hospital cardiac arrest (OHCA) carries a high mortality rate, and the most frequent aetiology is 
cardiac disease (1,2). The 30-day survival rate in Norway is 14% (3) Cardiopulmonary resuscitation 
(CPR) is a means to deliver partially oxygenated blood to vital organs such as the brain and the heart, 
to prevent irreversible hypoxic damage (4). Anoxic brain damage is the most common cause of 
mortality after admission to hospital in these patients (5). 
  
The gold standard treatment of out-of-hospital cardiac arrest are advanced cardiovascular life support 
(ACLS) as described in the guidelines from resuscitation authorities such as the Norwegian 
Resuscitation Council (6) or the European Resuscitation Council (7) (Figure 1).  
 
 
 
Figure 1. Guidelines from the European Resuscitation Council 
 
In Norway, approximately 22% of OHCA present with a shockable rhythm – ventricular fibrillation 
(VF) or ventricular tachycardia (VT) (8). In the cardiac arrest setting, it is well documented that 
immediate defibrillation is important if the presenting cardiac rhythm is VT or VF. According to the 
Norwegian national guidelines for CPR, a shock should be delivered every third minute if the rhythm 
is shockable (6). However, multiple attempts with defibrillation may be necessary to achieve return of 
spontaneous circulation (ROSC). 
 
In double sequential external defibrillation (DSED) two defibrillators are used simultaneously to 
convert the malignant arrhythmia (9). The first set of defibrillator pads are placed in the standard 
anterior-lateral position and the second set in the anterior-posterior position (Figure 2). The shocks are 
administered manually in quick succession, preferably less than one second apart (10).  
 

                       
 
 
Figure 2. Position of defibrillator pads in dual defibrillation.  
 
DSED has been described in case reports and observation studies without control groups (11–18) and 
in review papers (19,20). Lately, a randomized controlled trial (RCT) assessed the use of DSED in the 
prehospital setting (10), where either DSED or anterior-posterior placement of the defibrillation pads 
were compared to standard defibrillation strategy. In this study, the DSED strategy demonstrated 
significant increase in survival. However, in this RCT, DSED or anterior-posterior placement of 
defibrillation pads was not performed until 3 failed attempts, so-called refractory VF, resulting in a 
delay until alternative defibrillation strategy was attempted.  
 
Studies suggest that more than 50% of patients with shockable rhythm require more than 2 shocks to 
convert the malignant arrhythmia (21). It is well established that reduced time to ROSC is associated 
with improved outcome (22–24). Hence, DSED as the initial defibrillation strategy may seem 
reasonable.  
 
This study therefore aims to assess the use of early DSED as the strategy for defibrillation of OHCA 
patients with shockable rhythm.  
 
This protocol is designed according to the Standard Protocol Items: Recommendations for 
Interventional Trials (SPIRIT) 2013 guidelines and will be reported according to the Consolidated 
Standards Of Reporting Trials 2010 Guidelines (25,26). 
 
Potential eligible patients   
 
The number of OHCA incidents in Norway in 2022 was 3 881, which correlates to an incidence of 
71/100 000 inhabitants per year, increasing from 60/100 000 in 2017 (3,8). The number of patients 
with OHCA that present with a shockable rhythm in Norway is more than 650 (3). The annual number 
of patients in Norway that receive 2 or more defibrillations by ambulance personnel, and therefore 
eligible to a strategy of early DSED, is currently unknown. However, according to the findings by 
Hasegawa et al (21), more than 400 patients may be eligible every year in Norway. The exact number 

                       
of potential eligible patients will be sought investigated in cooperation with the Norwegian Cardiac 
Arrest Registry.  
 
Study rationale  
 
The aim of the study is to assess use of early DSED as part of the ACLS treatment in OHCA. The 
study will assess survival and neurological outcome in surviving patients. The trial does not test 
specific medical equipment, nor compares the effect of different defibrillators.  
 
The use of DSED is already investigated in a randomised controlled trial setting (10). Safety of both 
patient and medical equipment has also been investigated, without clear evidence for patient or 
equipment harm (10,27,28).  
 
DSED may be a superior defibrillation strategy due to several reasons, or combinations of these 
(10,29):  
 
1) increased energy (Joule) delivered at each defibrillation  
2) lowered threshold in the myocytes for the second shock  
3) a current vector change that may result in higher amount of energy (Joule) to the posterior 
parts of the heart muscle where cardiac fibrillation is more likely to originate.  
 
This trial will supplement the data from earlier trials (10), however will potentially be the first to 
assess early DSED as defibrillation strategy, to all patients with shockable rhythms. Hence, the trial 
seeks to contribute as research to improve current best practice.  
  
Academic study  
 
 
This study is not part of an application for regulatory approval of medical devices. It is not conducted 
to establish or verify the clinical benefits of a defibrillator device as specified by its manufacturer. No 
defibrillator manufacturer is involved in the design of the trial or the trial itself, nor will any 
manufacturer gain access to data or results other than those publicly published. The Sponsor retain 
ownership of all data and results generated through this trial. The trial is not designed to report any 
alteration of CE-markings or any other regulatory application for any defibrillator devices.  
 
6. Objectives and endpoints  
 
Primary objective 
The primary objective is to assess the efficacy of DSED as an initial treatment in patients with out-of-
hospital cardiac arrest (OHCA), measured as primary endpoint: Survival with admission to hospital.  
 
Secondary objective  
Secondary objectives of this trial are to evaluate the effect of DSED on 30-day survival and 
neurological status at 30 days.   

                       
 
Primary endpoint  
 
The primary endpoint of this study is the proportion of patients admitted to hospital.  
 
Secondary endpoints  
 
 
30-day survival with neurological status defined as modified Rankin scale (mRS) score 0-3 
(Figure 3)  
 
Successful termination of the arrhythmia  
 
 
 
 
Figure 3. The modified Ranking scale.  
 
Exploratory endpoints 
 
All-cause mortality one year after randomisation  
 
Incidence of all patient-related adverse effects  
 
Incidents of malfunction of defibrillators after DSED 
 
7. Study population  
 
Selection of participants  
 
The patient population is adult patients (18 or older, as estimated by medical personnel on-scene) 
suffering from an out-of-hospital cardiac arrest.  
 
Inclusion criteria  
 

                       
The subject must meet all the following criteria to be included in the trial:  
 Estimated age 18 or older   
 Out-of-hospital cardiac arrest with shockable rhythm  
 
Exclusion criteria  
 
Fulfilling one criterion excludes the subject to be included in this trial. 
 Known do-not-resuscitate order  
 Obvious ethical reasons not to initiate or continue resuscitation  
 Pregnancy, obvious or suspected   
 Incarcerated patients  
 
Criteria for withdrawal or discontinuation  
 
Patients can withdraw from the clinical study at any time without the need of a rationale and without 
compromise to their future medical care. If the patient has not regained ability to give consent, the 
next-of-kin can withdraw the patient from the study at any time. All patients will receive the same 
standard of care.  
 
Any safety data on adverse events registered in patients that withdraw from the study will be stored in 
the database in an anonymized form, to ensure that no safety information is lost.  
 
Patients that withdraw or are withdrawn from the study after randomisation will be replaced. 
 
Enrolment  
 
Subjects with out-of-hospital cardiac arrest in the areas serviced by the study centres are candidates for 
enrolment into the study. Patients who develop cardiac arrest while being treated for other causes by 
ambulance personnel are also eligible.  
 
8. Informed consent process  
 
Eligible patients cannot provide informed consent before inclusion due to the cardiac arrest. Hence, 
inclusion to study will be performed before the patient or next-of-kin can provide informed consent or 
withdraw from the study.  
  
In accordance with national regulations and as currently applied in studies on cardiac arrest patients, 
the patient’s next-of-kin will be asked for an informed consent. However, during the resuscitation 
informed consent cannot be obtained, both because ambulance personnel are occupied with 
resuscitation of the patient and because it is expected that the next-of-kin is in a mental state where 
such information may be difficult to process. The next-of-kin will therefore be asked for a deferred 
consent, and they will be contacted as soon as possible after the incident. All information will be given 

                       
by someone experienced in communication with next-of-kin to patients with critical illness. If the 
patient regain capacity to provide an informed consent within 90 days, he/she will be asked for a 
deferred consent. Informed consent may be signed on paper or by a digital solution, as approved by 
the regional ethical committee (REC).  
 
This adheres to the ethical principles that have their origin in the Declaration of Helsinki (30). Prior to 
study start, all written information intended to subject or next-of-kin has been approved by the REC. 
The responsible investigator at the study site and/or a designee (collectively named site investigator 
(SI)) will explain the clinical study to the subject/next-of-kin as well as provide a copy of the subject 
information sheet. This sheet will include all aspects of the clinical study that are relevant to the 
subject’s/next-of-kin’s decision to participate. The sheet will be written in a non-technical and easily 
understood language.  
  
The SI is instructed to avoid coercion, not to appear to waive the subject’s legal rights in any way, to 
allow sufficient time for questions about study details and allow the subject/next-of-kin to make an 
informed decision to participate or not in the clinical study. 
 
In case of consent to participation, the informed consent form is signed and dated, and a copy is 
provided to the subject. A digital solution for informed consent will be available, through the eFORSK 
solution, handled by KlinForsk, the Clinical Research Unit, Central Norway. The information in this 
digital solution is identical as the written consent forms.  
 
9. Statistics  
 
The study will follow a group sequential design with adaptive sample size modification. This allows 
possible early stop of the study, in case of significant differences in the primary endpoint or 30-day 
survival rate between the groups. It also allows re-estimation of the sample size at the interim analyses 
to maintain the desired statistical power. Adaptive design is used in clinical research because it may 
contribute to study cost-effectiveness regarding time and money, may require fewer participants and is 
a safety aspect hence an important ethical argument (31–34). 
 
Statistical hypothesis 
 
Null hypothesis H0: There is no difference in survival to hospital admission between the control group 
(single defibrillation strategy) and the intervention group (dual sequential external defibrillation 
strategy).  
 
Alternative hypothesis HA: There is a difference in survival to hospital admission between the control 
group (single defibrillation strategy) and the intervention group (dual sequential external defibrillation 
strategy).  
 

                       
Sample size  
In Norway, 3881 patients suffered an OHCA in 2022, of which 22 % presented with a shockable 
rhythm (3). It is reported that 50% of patients receive more than one defibrillation shock (21), which 
results in 420 patients in Norway annually.  
 
The number of patients with both two or more defibrillation shocks and survival to hospital admission 
in Norway is not reported in known literature. A need assessment study to investigate this will be 
sought performed during 2024, as part of Dr Vegard Nordvistes PhD thesis.  
 
However, preliminary estimates using available data from the Norwegian Cardiac Arrest Registry 
indicate that expected survival to hospital admission in this patient cohort is approximately 50%. The 
sample size needed to demonstrate a clinically relevant increase from 50% to 65% survival to hospital 
admission, with 0,80 power and a significance level of 0,05 is 169 patients in each group, total 338 
patients.  
 
We estimate a 5% drop-out from the study and therefore choose to include a total of 356 patients in the 
study, 178 patients in each group.  
 
Interim analyses 
One interim analysis will be performed, after 90 patients in both the intervention and the control group 
are included. There is no specific time schedule for the interim analysis. The variables that should be 
assessed is the primary endpoint and 30-day survival with good neurologic outcome.  
An external data monitoring committee will perform the interim analysis and may consider a 
recommendation to the Sponsor to stop the trial if a difference in primary endpoint or 30-day survival 
between the groups, with a significance level following the O´Brien-Fleming approach is found 
(35,36).  
At the interim analysis, we will re-estimate the sample size. Based on an assumption that any 
difference in the primary endpoint between the two groups will persist, we will recommend the 
sponsor to consider stopping the trial due to futility if the new sample size needed to prove a 
difference is more than three times the planned sample size (with 0.80 power and a significance level 
of 0.05).  
 
Measures to minimize bias  
Selection bias  
This is a randomised study, which is important to minimise selection bias. Randomisation procedure is 
described in the section “Randomisation procedure”.   
 
Performance bias  
The treatment post-ROSC or after hospital admission will not differ between the groups. This will 
minimize performance bias.  
 
Exclusion bias  
Exclusion bias is mitigated using limited number of personnel to obtain informed consent and to check 
survival and other patient data. The same personnel are used for registration of data into the case 
report form (CRF).  

                       
 
Statistical design 
Statistical analysis will follow the intention-to-treat (ITT) principle. The outcome between participants 
randomised to the intervention group (DSED strategy) and the control group (single defibrillation 
strategy) will be analysed, for all patients where defibrillation has been performed. Per-protocol 
analyses will be considered if more than 10% of patients in the intervention group that received 
defibrillation did not receive DSED but single defibrillation. This means that a considerable amount in 
the intervention group has deviated from protocol and may therefore undermine the validity of the ITT 
analysis.  
 
Hypothesis testing will be used to analyse the primary endpoint and other dichotomous secondary 
endpoints. Any continuous variables will be analysed by regression methods.  
 
The level of significance and power of the clinical study 
One RCT demonstrate that DSED improve survival (10), however it is possible that DSED, and the 
inclusion to a study itself, may contribute to decrease the chance of good outcome. Therefore, we will 
use a two-sided test with significance level of 0.05 for the analyses. A significance level following the 
O´Brien-Fleming approach is chosen on the interim analysis (35,36).  
 
Expected drop out rates 
Inclusion to study is performed prior to informed consent. Based on earlier experience with cardiac 
arrest studies in Norway we expect a low dropout rate, estimated to 5%.  
 
Specification of exploratory subgroups 
Subgroups of patients may have enhanced or reduced effect of the intervention. To assess possible 
modifiers of the intervention effect, exploratory analyses will be used:  
 
Age  
 
Sex  
 
Time from debut of arrest to defibrillation   
 
Study site  
The subgroups will be analysed by generalised linear models, which includes multiple regression 
analyses. This enables multiple imputation if necessary.   
 
Treatment of missing data 
Missing data will be reported in the publication and multiple imputation may be considered.   
 
Min/max number of subjects per centre  
There is no minimum or maximum number of subjects per study site.   
 

                       
10. Project methodology and overall design 
The purpose of the study is to assess the efficacy of DSED as a strategy as part of the ACLS provided 
in treatment of OHCA. This trial will not test any medical device, nor compare the effect of different 
medical devices. 
 
This is a prospective, cluster randomised, parallel group, crossover, multi-centre, clinical trial. Study 
sites are randomised in a 1:1 ratio to include patients to either the control group or the intervention 
group. After 6 months, crossover to the other study arm will be performed. After these 6 months a re-
randomisation is performed, and the study site will be allocated to either the control group or 
intervention group. This will continue to the end of study or to the study site withdraw from the study 
(Figure 4).  
The control group will receive ACLS according to national guidelines. The intervention group receives 
ACLS according to national guidelines, with defibrillations performed as DSED.    
 
 
 
 
Figure 4. Flow-chart of patient allocation and inclusion  
 
Blinding of the ambulance crew to the intervention is impossible due to the nature of the intervention. 
The study is estimated to last for 8 years. This includes start-up and education of the study centres, 
enrolment of patients, evaluation of last included patient one year after randomisation and a period of 
five years for retention of study documentation.  
 
Expected study duration 
The trial period is one year after inclusion for each study participant. The survival rate after 30 days 
will be registered and all-cause mortality one year after inclusion will be registered, after a chart 
review.  
 
Part I  
The first part of the trial will commence summer 2024 and last for two months. Three ambulance 
bases in Trondheim, Norway, will include patients to the intervention group during these two months. 

                       
Any modifications to the trial’s operating procedure and/or changes in the CRF will be performed 
before the second part of the trial can start. If Part I demonstrate need for significant change to the 
study protocol or lack of compliance to protocol by the ambulance bases, the included patients in Part 
I will not be added to the intervention group in the main part of the study, Part II.  
 
Part II  
This is the main part of the trial and will include no more than 50 ambulance bases, 25 to the 
intervention group and 25 to the control group.  
We estimate that the second part of the trial will start 1st September 2024 and estimate that 3 years is 
necessary to include patients. This includes the time needed for education and training of ambulance 
and study personnel.  
 
Randomisation procedure  
Study sites will be randomly allocated in a 1:1 ratio between the two study groups. The study site will 
then include all eligible patients into the study group assigned, for 6 months. After 6 months cross-
over will be performed, so the study site will include patients to the other study arm for the next 6 
months. After these 6 months a re-randomisation will be performed (Figure 4).  
The study site randomisation will be performed by KlinForsk, Clinical Research Unit, Central 
Norway. The random allocation sequence is generated using a Microsoft Access data base by 
KlinForsk. No investigator has access to the allocation sequence.  
 
Medical devices in the study 
During ACLS, several medical devices are used for treatment and diagnosis. These devices will be 
used in both groups of this trial, as part of the normal set-up in ground ambulances. This includes 
several devices, such as mechanical chest compressions devices, monitoring equipment, ultrasound, 
venous catheters, intraosseous needles, supraglottic airways and other.  
 
The study sponsor takes no responsibilities in the funding, provision, approval, or other aspects 
regarding these devices.  
 
Each study site will use two identical defibrillators, Corpulse 3 (Corpuls, GS Elektromedizinsche 
Geräte, Germany).  
Other available defibrillators may be used during the trial.  
 
11. Study procedures  
Treatment 1 – the control group  
The control group will receive ACLS as described in the guidelines from the Norwegian Resuscitation 
Council (6).  
 
Treatment 2 – the intervention group  
The intervention group will receive the same treatment as the control group, with the exception that 
defibrillations will be as DSED. The standard operating procedure is described in the chapter “Outline 
of the DSED procedure” (Figure 5).  
 

                       
Education and training of personnel  
All personnel involved in this study that will include patients are regularly part of resuscitation teams 
both in real life and in scenario training. Therefore, no mandatory training program for ACLS is 
necessary for this trial.  
 
All personnel that will include patients, must participate in a training program to ensure compliance to 
the DSED standard operating procedure. Participants must complete and pass this training program to 
include patients into the intervention group. Participants without proper training in DSED may still 
include patients in the control group.  
 
Outline of the DSED procedure  
Two defibrillators are placed side by side, preferably on the patients left side. The first ambulance 
worker identifies cardiac arrest and initiates CPR. The second ambulance worker turns on the 
defibrillators and readies two sets of pads. The first two pads are placed according to existing 
guidelines, i.e., in anterolateral position while chest compressions are ongoing. The third pad is placed 
in sternal position. The patient is logrolled, the left side of the posterior torso is exposed, and the fourth 
pad is placed in subscapular position before the patient is returned to supine position. To enable this, a 
maximum of 20 second pause in chest compression is allowed. The cardiac rhythm can be identified, 
and shocks delivered if appropriate (Figure 5).  
 
 
 
 
Figure 5. Standard operating procedure for dual defibrillation set-up.  
 
Follow-up  
The SI (principle investigator at study site or research employee) will follow up patients admitted to 
hospital until 30 days after inclusion.  

                       
The SI will perform a chart review after one year to assess one-year mortality and register the result in 
the CRF.  
 
Follow-up medical care  
All patients will receive standard care after inclusion to the study.  
 
Discontinuation of the study  
The trial may be stopped by the sponsor in the event of any of the following:  
 
Occurrence of adverse event (unknown to date) in respect of their severity, nature or duration.  
 
Loss of study funding  
 
Low inclusion rate  
 
Ethical or medical reasons that affect the continuation of the study  
 
If the interim analysis demonstrates significant group difference in the primary endpoint or 30-day 
survival with good neurologic prognosis, the sponsor may decide to stop the study. Recommendation 
to stop the study should only happen after a face-to-face meeting with the project management.  
 
The study site primary investigator may stop or terminate the study at his/her study site, at any time.  
 
The data monitoring committee (DMC) can recommend the sponsor to stop or terminate the study if 
they find severe or unsolvable safety issues.  
 
Laboratory test  
We will not analyse blood samples in this study.  
 
12. Data collection and handling 
 
Data handling  
Data will be registered into a web-based case report form (CRF),through the eFORSK solution, 
(https://www.klinforsk.no/info/Informasjon) handled by the department KlinForsk, Clinical Research 
Unit, Central Norway. KlinForsk is authorised as data processors by the Norwegian Centre for 
Research Data. KlinForsk will set up necessary accounts to permit access to the CRF. 
 
Source data 
Data may be gathered from:  
 
 
Ambulance journal and air ambulance journal  
 
Utstein prehospital cardiac arrest journal  
 
Data file from the defibrillator used  
 
Electronic patient journal  
 
Interview with the patient/next-of-kin  

                       
 
Storage of study documentation  
Electronically data (i.e., ultrasound images, pictures, patient monitor files) will be stored in a separate 
folder in the Microsoft Teams application, connected to the users at St. Olavs Hospital. Access to this 
folder will be restricted to authorized users only on a need to know and need to do basis.  
 
Hard copies of any patient documents that may include identifiable information will be stored at the 
investigator site file (ISF), at a locked location at each study site or at the coordinating study site at 
Rosten, Trondheim. Only the site investigator and study employee at the study site have access to this 
ISF.  
 
Original study trial documents will be stored at the study sites or at the coordinating study site at 
Rosten, Trondheim, for five years to allow for inspection by relevant authorities. The site 
investigator will maintain confidentiality of the data and prevent accidental destruction of such 
documents.  
 
Data collection  
Data will be registered according to this schedule:  
 
 
Table 1. SPIRIT data schedule.  
 
These data points will be registered:  
 
All patients - data reported after inclusion 
Age 
 
Gender  
 
Location of the incident 
Public outdoors, public indoors, private 
indoors 
Medication and dose used during resuscitation  
 

                       
Route of administration 
Intravenous, intraosseous 
All relevant times 
DD.MM.YYYY: hh:mm 
Time of dispatch  
 
Time of arrival  
 
Time of first defibrillation  
Time of first termination of shockable 
rhythm  
Time of first ROSC  
Time of sustained ROSC 
 
Number of defibrillations, DSED or single  
n  
Number of defibrillations before DSED 
n 
Compression machine used 
yes/no 
Airway management (main method)  
Supraglottic airway, Endotracheal 
intubation 
ROSC more than 20 minutes 
yes/no 
Data file from monitor used   
 
Signs of life during CPR 
yes/no 
 
Delivered to hospital - additional data 
Survival to hospital discharge
Yes/no  
Modified Rankin scale at day 30 
0 to 6 
Survival one year after randomisation 
yes/no 
 
 
Data review and editing  
Each included patient will be given a unique study number and data will be identified only by the 
study number. The site investigator or designee will handle an enrolment log (Subject ID log and 
Screening log, in Appendix) which include the patients name, date of birth and study number. These 
logs will be stored separately at each study site. Identifiable data will not be registered in the CRF.  
 
If a SI for any reason must withdraw from the trial, his/her responsibility is transferred to the project 
management, which, if necessary, will appoint a new investigator.   
 
13. Study management  
The study will be performed according to the ICH GCP Notes for Guidance on Good Clinical 
Practice (CPMP/ICH/135/95). All study sites will have a system for data monitoring, and data 
management and retention. Individual patient data records will be handled according to the 
legislation of each participating country.  
 
14. Study amendments  
This research protocol may require amendments during study. Any amendments will be agreed upon 
between the project management and sponsor and be approved by REC and other relevant authorities.  
 

                       
15. Ethics Committee Approval 
The study will not start before approval by the ethics committee is granted. This approval will apply 
for all Norwegian study sites.  
Any foreign study sites must be approved by their regional or national ethics committee, prior to 
patient inclusion. All sites must comply with local regulations, national and EU law.  
 
16. Other Regulatory Approvals 
Sites outside of Norway may be need national regulations in conjunction to European Union 
Regulation 2017/745 on medical devices. In such instances, the necessary approvals must be in place 
prior to site opening. These applications are the responsibility of the foreign site’s investigator. 
 
17. Trial insurance  
In Norway, all patients who participate in the study are covered by Norwegian System of Patient 
Injury Compensation (Norsk Pasientskadeerstatning), a government agency subject to the Norwegian 
Ministry of Health and Care Services. Details are found at http://www.npe.no/en/.   
Any foreign study sites must ensure insurance cover for any included patients and provide the project 
management with documentation prior to opening the study site.  
 
18. Trial organisation  
Organisation  
The research responsible institution (Sponsor) is the Clinic of Cardiology, St. Olavs University 
Hospital. The main funder is the Norwegian Air Ambulance Foundation. An external data monitoring 
committee is independent from the project management and will communicate directly to the sponsor 
or the project management as appropriate (Figure 6).  
 
 
 
Figure 6. Trial organisation  
 

                       
The project management  
These are the personnel most involved with the day-to-day handling of the study. They will have face-
to-face meetings at need, no less than every 6 months. Members of the project management are listed 
in chapter 2, Project management.  
 
19. Data monitoring committee 
An independent Data Monitoring Committee (DMC) will be established and be governed by a charter 
based on the NorCRIN standard operating procedure. This charter will describe the roles and 
responsibilities of the DMC. The charter and DMC should be in place before inclusion of the first 
patient.  
 
20. Funding  
This trial is funded mainly by the Norwegian Air Ambulance Foundation. Research grants or funders 
may be involved during the study period. None of the funders will contribute to the study design, 
collection, management, analysis, or interpretation of data, nor writing of the report or decision to 
submit the report to publication. The sponsor retains full ownership of all data generated in the trial. 
 
21. Conflict of Interest 
The sponsor has no conflict of interest in relation to any defibrillator device or manufacturer in this 
trial.  
 
VN, AJK, MR, JD and JRB have no financial conflict of interest. VN, AJK, MR and JRB are partly 
funded by the Norwegian Air Ambulance Foundation for research purposes.  
 
22. Publication policy 
The study protocol will be submitted for publication in an international peer reviewed journal.  
When the study is completed, the results will be submitted for publication in an international peer 
reviewed journal, as well as submitted to the REC according to national regulations.  
 
Authorship of the primary publication is decided by the project management and granted according to 
the Vancouver definitions ((37). Personnel with significant contribution, but not fulfilled the criteria to 
authorship, will be mentioned under “Acknowledgements”. Study sites that recruit > 30 participants 
will be entitled to one name, > 60 participants will be entitled to one additional name, > 90 two 
additional names. If a study site includes less than 30 patients, the site will not be entitled to an author 
name.  
The main publication will report the primary and secondary endpoints.  
 
 

                       
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