"A Randomized Trial Assessing the Effect of Early Double Sequential Defibrillation With Anterior-posterior and Anterior Lateral Pad Placement and Sequential Defibrillation Compared to Standard Pad Placement and Single Defibrillation in Patients With Out of Hospital Cardiac Arrest With Initial Shockable Rhythm and at Least One Failed Standard Defibrillation"
Phase: PHASE2
Conditions: Out of Hospital Cardiac Arrest, Ventricular Fibrillation, Defibrillation, CPR, ACLS, Sudden Death
Sponsor: Gabriel Riva

Clinical Investigation Plan 
Study Code: 
Double-D Main Trial  
SIN/CIV-ID: 
CIV-25-01-051015 
 
CLINICAL INVESTIGATION PLAN 
 
DOUBLE-D TRIAL 
 
Early Double sequential Defibrillation in Out-of-Hospital Cardiac Arrest 
 - A Randomised study 
 
“A randomised trial assessing the effect of early double 
sequential defibrillation with anterior-posterior and anterior lateral 
pad placement and sequential defibrillation compared to standard pad 
placement and single defibrillation in patients with Out-of-Hospital Cardiac 
Arrest with initial shockable rhythm and at least one failed standard 
defibrillation” 
 
 
CIV-25-01-051015 
Date:  
2025 - 12 – 05 
Sponsor:  
Centre for resuscitation science, Karolinska Institutet, 
Department of 
clinical science and education, Södersjukhuset, 
Sjukhusbacken 10, 118 83 Stockholm 
Tel: 08-6161000 
Sponsor representative  Gabriel Riva, MD, PhD 
 
Centre for resuscitation science, Karolinska Institutet, 
Department 
of clinical science and education, Södersjukhuset, 
Sjukhusbacken 10, 118 83 Stockholm 
Tel: 070-5452086 
 
 
Document version 
Date of Issue 
Summary of Change 
2.0 
2025-12--05 
- 
 
 

 
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Table of Contents 
Table of Contents ................................................................................................................... 2 
Signatures ............................................................................................................................... 5 
Contact information ................................................................................................................ 6 
Funding and research agreement ............................................................................................ 8 
List of used acronyms and abbreviations ............................................................................... 9 
1. 
Synopsis ..................................................................................................................... 11 
2. 
Identification and description of the investigational device ...................................... 14 
2.1. 
Description of the investigational devices ........................................... 14 
2.2. 
Intended purpose ................................................................................ 18 
2.3. 
Manufacturer of the investigational device ......................................... 20 
2.4. 
Model/type .......................................................................................... 20 
2.5. 
Target population ................................................................................ 20 
2.6. 
Summary of required training/experience needed .............................. 20 
3. 
Background and justification for the design of the clinical investigation ................. 21 
3.1. 
Background ........................................................................................ 21 
3.2. 
Evaluation of results of prior testing, assessments and clinical 
investigations ...................................................................................................... 23 
3.3. 
Evaluation of clinical data ................................................................... 24 
4. 
Risks and clinical benefits of the investigational device and clinical investigation .. 24 
4.1. 
Expected clinical benefits ................................................................... 24 
4.2. 
Anticipated adverse device effects ..................................................... 25 
4.3. 
Risks associated with participation in the clinical investigation .......... 25 
4.4. 
Possible interactions with concomitant medical treatments ............... 26 
4.5. 
Steps to be taken to control or mitigate risks ...................................... 26 
4.6. 
Rationale for benefit-risk ratio ............................................................. 27 
5. 
Objectives and hypotheses of the clinical investigation ............................................ 27 
5.1. 
Objectives ........................................................................................... 27 
5.2. 
Hypotheses ......................................................................................... 28 
6. 
Design of the clinical investigation ........................................................................... 28 
6.1. 
General information ............................................................................ 28 
6.2. 
Endpoints ............................................................................................ 29 
6.3. 
Subjects .............................................................................................. 29 
6.4. 
Methods to minimise bias ................................................................... 30 

 
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6.5. 
Unblinding ........................................................................................... 30 
6.6. 
Description of the clinical procedures and diagnostic methods relating 
to the clinical investigation .................................................................................. 30 
6.7 Participating Trial sites ................................................................................. 33 
6.8. End of the clinical investigation ................................................................... 35 
6.9. Monitoring plan ............................................................................................ 35 
7. 
Statistical considerations. .......................................................................................... 35 
7.1. 
Analysis population ............................................................................. 35 
7.2. 
Descriptive statistics ........................................................................... 36 
7.3. 
Analytical procedures ......................................................................... 36 
7.4. 
Sample size calculation ...................................................................... 37 
7.5. 
Missing data ....................................................................................... 38 
7.6. 
Exploratory analysis and sensitivity analysis ...................................... 38 
7.7. 
Data safety monitoring board (DSMB) ................................................ 38 
7.8. 
Reporting deviations ........................................................................... 39 
7.9. 
Handling of imbalance of subjects per site ......................................... 39 
8. 
Data management and protection .............................................................................. 39 
8.1. 
Data collection and Case Report Forms ............................................. 39 
8.2. 
Data storage ....................................................................................... 43 
8.3. 
Archiving ............................................................................................. 44 
8.4. 
Data protection ................................................................................... 44 
9. 
Amendments to the CIP ............................................................................................. 45 
10. 
Deviations from the CIP ............................................................................................ 45 
11. 
Device traceability and accountability ....................................................................... 45 
12. 
Statements of compliance .......................................................................................... 45 
12.1. 
Compliance to the investigational plan, good clinical practice, and 
regulations .......................................................................................................... 45 
12.2. 
Ethical review of the clinical investigation ........................................... 46 
12.3. 
Insurance ............................................................................................ 46 
13. 
Informed consent process .......................................................................................... 46 
13.1. 
General process for informed consent ............................................... 46 
13.2. 
Consent process ................................................................................. 47 
14. 
Adverse events, adverse device effects and device deficiencies ............................... 49 
14.1. 
Definitions ........................................................................................... 49 
14.2. 
Recording and Reporting .................................................................... 50 
14.3. 
List of foreseeable Adverse events .................................................... 53 
14.4. 
Monitoring ........................................................................................... 53 

 
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15. 
Premature termination of the clinical investigation ................................................... 53 
16. 
Publication policy ...................................................................................................... 54 
16.1 Authorship of the first publication ............................................................... 54 
17. 
Bibliography .............................................................................................................. 56 
 
 
 

 
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Signatures 
Sponsor  
I am responsible for ensuring that this CIP includes all essential information to be 
able to conduct this clinical investigation. I will submit the CIP and all other important 
clinical investigation-related information to the responsible investigator(s) so that they 
can conduct the clinical investigation correctly. I am aware that it is my responsibility 
to hold the staff members who work with this clinical investigation informed and 
trained. 
Sponsor’s signature 
Date: 2025-12-12  
Gabriel Riva (digital signature at the bottom) 
Coordinating Investigator  
I have read this CIP and agree that it includes all essential information to be able to 
conduct the clinical investigation. By signing my name below, I agree to conduct the 
clinical investigation in compliance with this Clinical investigation plan, the 
Declaration of Helsinki, SS-EN ISO14155:2020 (Good Clinical Practice), and the 
current national and international regulations governing the conduct of this clinical 
investigation. 
I will submit this CIP and all other important clinical investigation-related information 
to the staff members and investigators who participate in this clinical investigation, so 
that they can conduct the clinical investigation correctly. I am aware of my 
responsibility to continuously keep the staff members and investigators who work 
with this clinical investigation informed and trained.  
I am aware that quality control of this clinical investigation will be performed in the 
form of monitoring, audit, and possibly inspection. 
Coordinating Investigator’s signature 
Date: 2025-12-12 
Akil Awad (digital signature at the bottom) 
 
 

 
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Contact information 
Role 
 
 
Sponsor  
 
Centre for resuscitation science, Department of clinical 
science and education, Södersjukhuset, Karolinska 
Institute 
 
Address: Sjukhusbacken 10, 118 83 Stockholm, Sweden 
Phone number: (+46) 08-616 10 00 
 
Contact person: Gabriel Riva, M.D., Ph.D. 
 
Mail: gabriel.riva@ki.se 
Phone number: (+46) 070 545 20 86 
 
 
 
Central Coordinating 
Investigator 
 
Akil, Awad, M.D., Ph.D. 
 
Centre for resuscitation science, Department of clinical 
science and education, Södersjukhuset, Karolinska 
Institute 
 
Address: Sjukhusbacken 10, 118 83 Stockholm, Sweden  
 
Mail: akil.awad@ki.se 
Phone number: (+46) 070 400 13 63 
 
 
Emergency contact 
details, Sponsor and 
Sweden 
 
 
Gabriel Riva, Representative of Sponsor 
 
Mail: gabriel.riva@ki.se 
Phone number: (+46) 070 545 20 86 
Akil Awad, Coordinating Investigator 
Mail: akil.awad@ki.se  
Phone number: (+46) 070 400 13 63 
 
 
 
Emergency contact 
details, The 
Netherlands 
 
 
Christian Van der Werf 
ARREST (AmsteRdam REsuscitation STudies) 
 
Adress: Amsterdam UMC  
Mail: c.vanderwerf@amsterdamumc.nl 
Phone number: (+31) 6 14425804 

 
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Emergency contact 
details, Spain 
 
 
Fernando Rosell M.D. 
 
Mail: fernandorosell@gmail.com 
Phone number: (+34) 697 95 86 89 
 
 
Principal Investigators 
for each participating 
site, Sweden 
 
1. Carl Magnusson, R.N., Ph.D. 
Local PI: Sahlgrenska University Hospital 
Mail: carl.magnusson@vgregion.se 
Phone number: (+46) 070 886 86 20 
 
2. Andreas Claesson, R.N., Ph.D. 
Local PI Alingsås, Lerum and Kungälv (”sjukhusen i 
väster”) 
Mail: Andreas.claesson@ki.se 
Phone number: (+46) 0704940546 
 
3. Kristoffer Wibring, R.N., Ph.D. 
Local PI Ambulanssjukvården Region Halland 
Mail: kristoffer.wibring@regionhalland.se 
Phone number: (+46) 076 721 40 07 
 
4. Per Wennberg, R.N. Ph.D. 
Local PI Ambulanssjukvården Skaraborgs Sjukhus 
Mail: per.wennberg@vgregion.se 
 
5. Carl Magnusson, R.N. Ph.D. 
Ambulanssjukvården NU-sjukvården  
Mail: carl.magnusson@vgregion.se 
Phone number: (+46) 070 886 86 20 
 
6. Linus Lilja, M.D., Ph.D. 
Local PI Ambulanssjukvården Region Värmland 
Mail: linus.lilja@regionvarmland.se 
Phone number: (46+) 010-83 157 16 
 
7. Emil Bergerum, R.N. 
Local PI Ambulanssjukvården Södra Älvsborgs Sjukhus 
Mail: emil.j.olsson@vgregion.se 
 
8. Patrik Martner, M.D.  
Local PI Prehospital Intensive Care Unit  
Mail: patrik.martner@vgregion.se 
Phone number: (+46) 070 485 77 52 
 
9. Knut Taxbro, M.D. Ph.D.  

 
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Local PI Ambulanshelikoptern Västra Götalandsregionen 
Mail: knut.taxbro@rjl.se 
Phone number: (+46) 070 675 34 57 
 
Principal Investigators 
for each participating 
site, The Netherlands 
 
1. Christian Van der Werf M.D. Ph.D. 
Local PI ARREST (AmsteRdam REsuscitation STudies) 
Amsterdam UMC  
Mail: c.vanderwerf@amsterdamumc.nl 
Phone number: (+31) 614 42 58 04 
 
Principal Investigators 
for each participating 
site, Spain 
 
1. Carlos Rubio Chacón M.D. PhD. 
Local PI SUMMA 112, Madrid 
Mail: carlos.rubio@salud.madrid.org 
Phone: (+34) 639 91 74 03 
 
2. María José Luque-Hernández MD. PhD. 
Local PI Centro de Emergencias 061, Malaga, Andalucia 
Mail: mariajose.luque.sspa@juntadeandalucia.es 
Phone: (+34) 617 56 33 52 
 
3. Xavier Francesc Jimenez Fabrega  
Local PI Sistema de Emergencias Medicas de Catalunya 
(Barcelona) 
Mail: francescxavierjimenez@gencat.cat 
Phone: (+34) 616 44 60 68 
 
4. Cristian Fernández Barreras MD 
Local PI Médico Emergencias Osakidetza 
EMERGENTZIAK, (Bilbao) 
Mail: cristian.fernandezbarreras@osakidetza.eus  
Phone: (+34) 699 68 11 82 
 
Funding and research agreement  
This is an academic design and financed study. Participating sites will in this trial take 
own economic responsibilities in taking their own costs. For this purpose, a resource 
certificate is signed. The defibrillators used in this trial are part of the participating 
sites standard equipment. A minor economical deal covering education, data 
management and defibrillation electrode pads used in the trial will be provided.  
 
 
 

 
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List of used acronyms and abbreviations 
Abbreviation 
Term/Explanation 
ALS 
Advanced Life Support 
ADE 
Adverse Device Effect  
AE 
Adverse Event 
A-L 
Anterior - Lateral 
A-P 
Anterior - Posterior 
AE 
Adverse Event 
CIP 
Clinical Investigation Plan 
CPC 
Cerebral Performance Category 
CPR 
Cardiopulmonary Resuscitation 
CRF 
Case Report Form  
DD 
Device Deficiency 
DSD 
Double Sequential Defibrillation 
DMC 
Data Monitoring Committee 
ECMO 
ExtraCorporeal Membrane Oxygenation 
ECG 
ElectroCardioGram 
EMS 
Emergency Medical Services 
GCP 
Good Clinical Practice 
GSPR 
General Safety and Performance Requirements 
IFU 
Instructions for Use 
ILCOR 
International Liaison Committee on Resuscitation 
SS-EN ISO 
Swedish Standard - European standard International 
Organisation for Standardisation  
ISF 
Investigator Site File 
ITT 
Intention-to-treat = including all data from all subjects who have 
participated in the clinical investigation 
MDCG  
Medical Device Coordination Group 
mRS 
Modified Rankin Scale 
OHCA 
Out-Of-Hospital Cardiac Arrest 

 
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PP 
Per Protocol analysis = including only data from subjects who 
have completed the clinical investigation completely in 
accordance with the CIP, with no deviations from the CIP 
ROSC 
Return Of Spontaneous Circulation 
SADE 
Serious Adverse Device Effect  
SAE  
Serious Adverse Event 
USADE 
Unanticipated Serious Adverse Device Effect 
VF 
Ventricular Fibrillation 
VT 
Ventricular Tachycardia 
 
 
 

 
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1. Synopsis 
 
Background and rationale 
and design: 
 
Background: Out-of-hospital cardiac arrest (OHCA) 
affects about 270,000 individuals in Europe annually.[1] In 
OHCA, presenting with ventricular fibrillation (VF) or 
pulseless ventricular tachycardia (VT) amendable to 
defibrillation are among the strongest predictors of 
survival.[2] If defibrillation can be performed successfully 
within the first 3-5 minutes, survival can be as high as 
70%.[3] However, some patients in VT/VF do not respond 
to initial defibrillation, and survival decreases with an 
increasing number of defibrillations required to terminate 
VT/VF.[4]  
 
In 2022, one prospective cluster randomised trial showed 
increased survival among OHCA patients in refractory VF 
using an alternative defibrillation strategy; either switching 
to anterior-posterior defibrillation pad placement (A-P) or 
Double Sequential Defibrillation “DSD” (using two 
defibrillators, one in the standard anterior-lateral position 
(A-L) and one in A-P position and defibrillation in rapid 
sequence), as compared to standard defibrillation pad 
placement.[5] Refractory VF was defined as VF that 
persisted despite three consecutive defibrillations with the 
defibrillation pads in the standard position.  
 
These results prompted the International Liaison 
Committee on Resuscitation (ILCOR) to release a 
statement of treatment recommendation on DSD on March 
6, 2023. It suggested that “…either vector change or DSD 
may be considered for adults with cardiac arrest who 
remain in VF or pulseless VT despite three defibrillations 
(weak recommendation, low certainty of evidence).” [6]  
Furthermore, if DSD was to be used, it should be 
performed with a methodology similar to that described in 
the trial by Cheskes et al.  
 
However, several questions remain. Knowledge gaps 
highlighted in the ILCOR statement included whether the 
results from this one cluster randomised trial could be 
reproduced in any other setting. Furthermore, since 
survival is inversely associated with the number of 
defibrillation shocks, if earlier application of DSD could lead 

 
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to even higher survival for patients not in refractory VF has 
never been studied.  
 
Study rationale: To evaluate whether an early DSD-
strategy could benefit all patients with VT/VF after the first 
shock, including those not in refractory VF, the Double-D 
trial was designed. If DSD proves to be superior to 
standard defibrillation in a broader cardiac arrest 
population, also among those not in refractory VF, it would 
have a large impact on how Advanced Cardiac Life 
Support (ACLS) should be performed.  
 
Design: This is an academic, investigator initiated, open-
label study with a randomised controlled trial (RCT) design 
and 1:1 allocation (1 DSD: 1 standard). Screening for 
inclusion will be performed in all cardiac arrests by 
participating EMS units when there are two study-specific 
defibrillators available on site. 
 
Study population: Adult OHCA patients with pulseless 
VT/VF at initial rhythm analysis, at least one defibrillation 
performed in standard A-L position without return of 
spontaneous circulation (ROSC).  
 
P: Adult patients, 18 years or older, with OHCA, initial 
shockable rhythm (VT/VF) and, at least, one defibrillation 
performed in standard position and ongoing CPR (no 
ROSC).  
 
I: Application of a second defibrillator with pad placement 
in the anterior-posterior (A-P) position as early as possible 
after the first shock and double sequential defibrillation 
after the following rhythm analysis if the patient is still in 
VT/VF. 
 
C: Standard defibrillation electrode placement (A-L) and 
routine defibrillation with one defibrillator after the following 
rhythm analysis if the patient is still in VT/VF. 
 
O: The primary outcome is 30-day survival.  
 
The trial will be conducted by participating ambulance units 
attending OHCAs. These units will perform screening for 
inclusion, randomisation, intervention or control treatment, 
and initial follow up. 
 

 
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Investigational device: 
Two Corpuls3 defibrillators OR two Stryker LifePak15 
defibrillators used together in a double sequential 
defibrillation  
 
Number of subjects: 
 
916 
 
 
Inclusion criteria: 
 
- OHCA patients with VT/VF and at least one defibrillation 
performed in standard (A-L) position 
 
 
Exclusion criteria: 
 
- Age < 18 years 
- Obvious pregnancy 
- Known preexisting Do Not Attempt Resuscitation order  
 
 
Study objectives: 
 
Primary objective: To compare 30-day survival with early 
double sequential defibrillation in OHCA patients with initial 
shockable rhythm, at least one defibrillation performed and 
ongoing CPR, to standard defibrillation. 
 
Secondary objective: To compare the proportion of 
ROSC, survival to hospital admission, survival to hospital 
discharge with favourable neurological function and long-
term survival with a strategy of early double sequential 
defibrillation, compared to standard defibrillation.  
 
Safety objective: To assess the safety of an early DSD 
strategy in terms of defibrillation performance. 
 
 
Study endpoints: 
 
Primary endpoint: 
- 30-day survival 
 
Secondary endpoints: 
- Any ROSC 
- Survival to hospital admission, defined as a patient 
admitted alive to a hospital ward (ICU or CCU unit) with 
spontaneous circulation 
- Survival to hospital discharge 
- Neurological function at hospital discharge (mRS) 
 
Other outcomes: 
- Survival to 90 days 
- Neurological function (mRS and CPC) at 30 days 
- Neurological function (mRS and CPC) and Health-related 
Quality of Life at 90 and 180 days 
- Termination of ventricular fibrillation 

 
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- Total time in ventricular fibrillation 
 
 
Planned duration of the 
clinical investigation: 
 
 
Q2 2025 – Q4 2029  
2. Identification and description of the investigational device 
2.1. 
Description of the investigational devices 
The standard treatment for OHCA to terminate VT or VF is external defibrillation in order to 
restore spontaneous circulation. According to the ERC guidelines, the electrodes are placed 
in an anterior-lateral (A-L) position. The defibrillators used in this trial will be Corpuls3 (used 
in Sweden and Spain) and LIFEPAK15 (used in The Netherlands and Spain). 
Corpuls3 
Corpuls3 is a defibrillator with functions including monitoring of cardiac rhythm and vital 
parameters, but also defibrillation, cardioversion, and pacing. It is part of the standard 
equipment in the EMS units in the participating sites stated above. 
 
The risk classification of Corpuls3 is non-invasive IIb. 
 
 
 
Image: Corpuls3 

 
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The Corpuls3 provides monitoring of cardiac rhythm and vital parameters as well as 
diagnostic and therapeutic functions for the treatment of emergency and intensive care 
patients. A 12 lead ECG function provides the user a comprehensive ECG, which can be 
optionally supplemented by ECG analysis software. 
Further monitoring functions include oxygen saturation measurement (pulse oximetry), 
carbon dioxide measurement (capnometry) and temperature measurement, in addition to 
non-invasive and invasive blood pressure monitoring. Corpuls3 provides the following 
therapeutic functions: 
• defibrillation 
• cardioversion 
• pacing 
Defibrillation with corpuls3 is performed with a Biphasic, positive rectangular waveform 4 
msec. (90 % energy) and a negative rectangular waveform 3 msec. (10 % energy) pulse. 
 
 
The defibrillator which operates with the Corpuls3-specific biphasic pulse has two operating 
modes: 
• automatic external defibrillation (AED mode) 
• manual defibrillation and cardioversion (manual mode) 
In AED mode, the user is assisted by an automated ECG analysis, verbal instructions 
(configurable) and a metronome (configurable). The defibrillation pulse is triggered by the 
user. 
In manual defibrillation mode, the user has full freedom of action and decision-making.  
Defibrillation is performed by applying disposable adhesive electrodes, so-called corPatch 
electrodes.  
The standard position of the corPatch electrodes is the A-L Position, but alternative electrode 
positioning, including A-P should be considered in refractory VF. 
 

 
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Image: Anterior-lateral (A-L, standard) corPatch electrode placement from Corpuls3 user 
manual 
 
The Corpuls3 is intended for measurement and monitoring of vital parameters in addition to 
defibrillation, cardioversion or cardiac pacing of patients in the preclinical and clinical field by 
qualified medical staff trained in the use of the device.  
Corpuls3 may only be operated by trained medical staff of, for example, hospitals, doctor’s 
offices and emergency medical services, as well as of authorities and public safety 
organisations. 
The qualified staff must be 
• trained in proper handling, use and operation of the device and of the approved accessories 
as well as be 
• trained in basic and advanced resuscitation measures (Basic Life Support and Advanced 
Cardiac Life Support).  
For further information please see attached Description and intended purpose 
Corpuls3. 

 
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LIFEPAK15 
LIFEPAK®15 is a defibrillator with functions including monitoring of cardiac rhythm and vital 
parameters, defibrillation, cardioversion, and pacing.[1, 2] LIFEPAK®15 devices are part of 
the standard equipment in the EMS units at the participating sites stated above.  
 
 
 
The risk classification of LIFEPAK®15 is non-invasive IIb.[3] 
The LIFEPAK®15 provides monitoring of cardiac rhythm and vital parameters as well as 
diagnostic and therapeutic functions for the treatment of emergency or critically ill patients. 
Further monitoring functions include oxygen saturation measurement (pulse oximetry), 
carbon dioxide measurement (capnometry) and temperature measurement, in addition to 
non-invasive and invasive blood pressure monitoring.  
Defibrillation is performed with a biphasic truncated exponential waveform.  
 

 
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The defibrillator which operates with the LIFEPAK®15 has two operating modes: 
- 
automatic external defibrillation (AED mode) 
- 
manual defibrillation and cardioversion (manual mode) 
In AED mode, the user is assisted by an automated ECG analysis, verbal instructions 
(configurable) and a metronome (configurable). The defibrillation pulse is triggered by the 
user. In manual defibrillation mode, the user has full freedom of action and decision-making. 
Defibrillation is performed by applying disposable adhesive electrodes. 
LIFEPAK®15 may only be operated by trained medical staff of, for example, hospitals, 
doctor’s offices and emergency medical services, as well as of authorities and public safety 
organisations. The qualified staff must be: 
- 
trained in proper handling, use and operation of the device and of the approved 
accessories 
- 
trained in basic and advanced resuscitation measures (Basic Life Support and Advanced 
Cardiac Life Support).  
The LIFEPAK®15 is CE marked for defibrillation in OHCA. The usage of this device with the 
DSD strategy falls under “use outside of intended purpose” and is therefore deemed “off-
label”. The device manufacturer was contacted to evaluate potential risks associated with the 
use of this device within the DSD approach. According to the statement by the manufacturer, 
usage of this device for a DSD strategy incurs a theoretic chance of device damage or 
malfunction. The device-associated risks of DSD are further analysed in section 4.2 and 4.3.  
For further information please see attached statement regarding LIFEPAK15. 
“3314911-030_int-eng_lifepak_15_operating_instructions “  
 
2.2. 
Intended purpose  
The intended purpose of defibrillators in cardiac arrest is to terminate VT or VF with external 
defibrillation to restore spontaneous circulation. This can be done by electrodes placed in 
standard anterior-lateral (A-L) position, but in some circumstances in the anterior-posterior 
(A-P) position. Using one defibrillator with either electrode position (A-L or A-P) is within the 
scope of the CE-mark of the investigational devices. This is all part of standard clinical 
practice and within the intended use of the investigational device.  
An alternative strategy is to use two defibrillators (both A-L and A-P electrode position) and to 
perform two defibrillations in rapid sequence, as soon as possible but not simultaneously, so 
called double sequential defibrillation (DSD). This strategy is, at least partially, outside the 
CE-mark.  
The intended purpose of the investigational device in this clinical trial is to terminate VT/VF 
by performing DSD as early as possible after the first defibrillation. To our knowledge this is 
the first clinical trial evaluating an early DSD strategy in cardiac arrest.  

 
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2.2.1 Performing DSD within the Double-D trial: 
In this trial, all patients will be connected to defibrillators with adhesive electrodes in standard 
A-L position (se image above). 
If another defibrillator (AED) is already attached to the patient at EMS arrival the EMS will 
remove the electrodes from the other defibrillator and attach electrodes in standard A-L 
position and connect them to Corpuls3 or LIFEPAK15 in all cases. This is all part of current 
routine practice.  
 
2.2.2. If randomised to intervention  
The electrodes from a second defibrillator (Corpuls3 or LIFEPAK15) are placed in the A-P 
posterior position during interruptions in chest compressions for ventilation, thus not 
interfering with the electrodes from the first defibrillator. Attachment of the second defibrillator 
electrodes shall be performed as soon as possible after randomisation. 
 
If the patient has VT/VF at the subsequent rhythm analysis (every two minutes during CPR) 
both defibrillators are charged simultaneously during chest compressions and shocks from 
the two defibrillators are delivered by one healthcare professional in rapid sequence, as soon 
as possible but not simultaneously, (A-L first, A-P second when possible) and CPR is 
immediately resumed (DSD strategy). A DSD strategy will be used for all subsequent 
defibrillations if the patient remains in VT/VF, until termination of resuscitation or a decision to 
transfer the patient to hospital. The total shock pause (hands off interval where no 
compressions are performed) is recommended to be less than 5 seconds. 
 
In summary:  
- First defibrillator is attached in A-L position.  
- Second defibrillator is attached in A-P position. 
- Both defibrillators are set to manual mode. 
- If VT/VF is present at the next rhythm analysis, chest compressions are resumed and both 
defibrillators are charged to maximal energy (200J Biphasic for Corpuls3, 360J for 
LIFEPAK15) 
- Defibrillations are performed sequentially (as soon as possible but not simultaneously, 
preferably A-L first, A-P second. 
 
2.2.3 If randomised to the control group,  
The ambulance crew team will continue Advanced Cardiac Life Support in accordance with 
the European Resuscitation Council (ERC) guidelines and local protocols. Defibrillation is 
performed with standard A-L electrode placement using one Corpuls3 or LIFEPAK15 
defibrillator. Maximal energy output should be used for second shock and beyond (200J 
Biphasic for Corpuls3, 360J Biphasic for LIFEPAK15). The 2025 ERC guidelines suggest that 
shifting the placement of electrodes to the anterior-posterior position (so called vector 
change) may be considered after three unsuccessful standard A-L shocks and refractory 
VT/VF. It lies within the decision capacity of the ambulance nurse or physician on site and 
local protocols to determine whether a vector change strategy may be conducted after three 
non-successful standard A-L shocks.  

 
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For both groups, in accordance with 2025 ERC guidelines, charging the defibrillator(s) before 
the rhythm check is an acceptable alternative, if this is in accordance with local practice and 
protocols. 
 
2.3. 
Manufacturer of the investigational device 
Corpuls3 (Sweden and Spain) 
Name: Corpuls, GS Elektromedizinische Geräte G. Stemple GmbH  
Address: Hauswiesenstraße 26 86916 Kaufering, Germany  
Contact, phone number: +49819165722-0, 
Mail: info@corpuls.com 
LIFEPAK15 (the Netherlands and Spain) 
Name: Stryker  
Address: 3800 E. Centre Ave. Portage, MI 49002 USA 
Contact, phone number: +1 800 327 0770 
Mail: medicalcustomerservice@stryker.com 
 
2.4. 
Model/type 
 
• 
Corpuls3 / LIFEPAK15 
 
2.5. 
Target population 
The target population for this trial is patients with OHCA and VT/VF after one defibrillation in 
standard A-L position. The defibrillators deliver energy through electrodes attached to the 
patient in A-L or A-P position. Defibrillation with Corpuls3 or LIFEPAK15 is compliant with 
relevant GSPR, please see attached files. 
2.6. 
Summary of required training/experience needed 
Corpuls3 or LIFEPAK 15 may only be operated by trained medical staff of, for example, 
hospitals, doctor’s offices and emergency medical services, as well as of authorities and 
public safety organisations. The qualified staff must be: 
• trained in proper handling, use and operation of the device and of the approved accessories 
as well as be 
• trained in basic and advanced resuscitator measures (Basic Life Support and Advanced 
Cardiac Life Support).  

 
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All EMS units in this trial provide ACLS care for OHCA and are trained in ACLS. In addition to 
this, all EMS organisations included in the study ensure that EMS crews are trained in double 
sequential defibrillation prior to participating in the trial. 
This is in practice done by: 
a) “Theoretical study concept course”. All EMS crews take a 20-minutes obligatory web-
course providing theory and methodology for the study and the intervention.  
b) Practical training. All EMS crews shall under the supervision of a certified ALS-instructor 
undergo practical training. This training includes application of defibrillation pads in the 
anterior-posterior position while making sure to minimise interruptions in chest compressions, 
performing defibrillation in manual mode and charging and defibrillating with two defibrillators 
in a sequential manner. During this training special attention will be given to delayed 
(sequential) defibrillation by one individual. All participants shall in front of an instructor 
demonstrate correct practical performance. Finally, to perform team training in ALS scenarios 
using the Double-D algorithm.  
The scenarios shall facilitate the early provision of a DSD with maintained safety for all 
personnel, while minimizing interruptions in chest compressions. All EMS crews will rehearse 
the CPR training including DSD training once a year.  
For details on EMS training protocol, please see attached “Double-D training prerequisites 
and procedure 250922_Final” 
 
3. Background and justification for the design of the clinical 
investigation 
3.1. 
Background 
 
Out-of-Hospital Cardiac Arrest is a major health issue affecting approximately 380 000 
persons in the U.S. and 270 000 in Europe each year.[4] Presence of VT or VF, which are 
amendable to defibrillation, at the first rhythm analysis is one of the strongest predictors of 
survival, with survival rates up to 10 times higher compared to patients found in asystole or 
pulseless electrical activity.[5, 6] 
 
However, not all patients presenting with VT/VF will respond to defibrillation. The term 
“refractory ventricular fibrillation” is used for cardiac arrest patients who remain in VT/VF 
despite 3 consecutive defibrillation shocks. Treatment recommendations for this condition 
include administration of drugs such as epinephrine and amiodarone, continuous CPR, and 
where available, consideration of transport with ongoing CPR to a facility capable of ECMO-
assisted CPR.[7] Importantly, survival of patients with VT/VF is inversely associated with the 
number of defibrillations required to terminate VT/VF.[8] Therefore, an intervention that could 
increase the rate of conversion from VT/VF into a perfusing rhythm earlier has the theoretical 
potential to increase survival. 
 

 
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Standard external defibrillation is provided by applying defibrillator pads in the anterior-lateral 
position (A-L) with the anterior pad placed to the right of the sternum, just below the 
clavicle and the lateral pad in the left mid-axillary line, approximately in level with a V6 ECG 
electrode. This position should be clear of any breast tissue, see fig A.[9]  
 
 
An alternative pad placement is the so-called anterior-posterior position (A-P) where the 
anterior pad is placed on the left side of the sternum, below the clavicle, and the second 
posterior pad is placed on the back, to the left of the spine, below the left scapula, see fig B.  
Advantages with A-L position include the possibility to perform defibrillation without adhesive 
defibrillation pads (not recommended during CPR since 2010), but it is also relatively easy to 
apply defibrillation pads during CPR without the need to move the patient, and application 
can be done while chest compressions are ongoing. 
 
One advantage with A-P position is the theoretical closer proximity between pads resulting in 
lower thoracic impedance, and that the pads are encircling the heart, i.e. more current is 
transmitted through the posterior parts of the heart. Disadvantages include the need to move 
the patient to apply the posterior pad, interruptions in chest compressions during application, 
and no visual control over the posterior pad during chest compressions.  
 
A-L pad placement has been compared to A-P placement in elective cardioversion of atrial 
fibrillation with conflicting results. However, more recent studies comparing A-L to A-P using 
modern biphasic rectilinear or truncated defibrillation waveforms have found A-L placement 
superior in this setting.[10]  
 

 
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An alternative defibrillation strategy with double sequential defibrillation includes the use of 
two defibrillators, one in the A-L position and one in the A-P position and defibrillation shocks 
in rapid sequence “Double Sequential Defibrillation” (DSD). 
 
 
Electrode pad placement in DSD 
 
Double sequential defibrillation was described in 1994 to treat induced ventricular fibrillation 
during electro-physiology studies, that where refractory to standard defibrillation.[11] 
Observational studies and case reports of DSD has provided conflicting results, but usually 
DSD was used as an “last resort” when all other therapies had failed [12]. However, in 2022, 
the first and only randomised trial demonstrated increased survival with a strategy of either 
switching from A-L to A-P or from A-L to DSD in refractory VF (defined as VF at three 
consecutive rhythm analysis despite standard A-L defibrillation). 
 
These results prompted the International Liaison Committee on Resuscitation ILCOR to 
release a statement of treatment recommendation on DSD on March 6, 2023. It suggested 
that “either vector change or DSD may be considered for adults with cardiac arrest who 
remain in ventricular fibrillation or pulseless ventricular tachycardia despite three 
defibrillations (weak recommendation, low certainty of evidence).” Further, if DSD would be 
used it should be performed with a methodology similar to that described Canadian trial. 
 
However, several questions remain. Knowledge gaps highlighted in the ILCOR statement 
included whether the results from this one cluster randomised trial could be reproduced in 
any other setting. Furthermore, since survival is inversely associated with the number of 
defibrillation shocks, whether earlier application of DSD could lead to even higher survival for 
patients not in refractory VF has never been studied. Finally, no randomised trial on DSD has 
evaluated neurological function at 90 and 180 days or Health related quality of life. 
3.2. 
Evaluation of results of prior testing, assessments and clinical 
investigations 
 
As stated above, DSD has already been tested in a previous randomised controlled trial in 
humans and may be considered in refractory VT/VF according to international guidelines. 

 
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The difference in this trial is to apply DSD after one failed defibrillation, before the VT/VF is 
considered refractory.  
 
DSD with Corpuls3 is considered to be technically safe according to manufacturer, please 
see attached file “231130_DSED_eng_Corpuls”.  
 
Double-D Pilot trial 
 
We have performed a pilot study (CIV-25-01-051015) using Corpuls3 including 40 patients 
with the aim of assessing the feasibility and safety of a randomised trial comparing early DSD 
to standard defibrillation at 4 pilot sites (Clinical trials NCT06447805). 
Randomisation in the pilot trial was 3:1 (3 DSD, 1 standard). The primary feasibility outcome 
was proportion of patients randomised before three defibrillations (target >80%). The primary 
safety outcome was defibrillation malfunction. 
 
In total, 40 patients were included between June 2024 and April 2025, 29 were randomised 
to DSD and 11 to standard. Of all patients, 32/40 were randomised before three 
defibrillations (80%). Cross-over occurred in 1 patient in the control group after five standard 
defibrillations and in one patient in the control group. Follow-up was 100%.  
 
In the pilot study, all defibrillators were checked for functionality via a self-test immediately 
after resuscitation and a test defibrillation as soon as possible after resuscitation following 
each DSD use. We have not had any reported adverse events or technical problems. No 
alarming safety risks regarding defibrillators or time delays have been observed. 
 
In conclusion, we found that randomisation to a strategy of early DSD was feasible and 
appears safe. Therefore, the Double-D main trial will use same methodology for ambulance 
training and intervention as in the pilot trial.  
 
In the pilot trial, patients who had received one defibrillation at any point during resuscitation, 
irrespective of first presenting rhythm, were included. This resulted in the inclusion of 14 
patients who had an initial non-shockable rhythm that later transitioned to a shockable 
rhythm during resuscitation and were included. The rate of ROSC among those patients was 
very low and only one patient survived to hospital admission. The low rate of survival in this 
group is also supported by observational data (3). Therefore, we do not believe this group will 
benefit significantly from DSD and therefore, to increase homogeneity of the study population 
in the main trial, we will only include patients with an initial shockable rhythm. 
3.3. 
Evaluation of clinical data 
 
Please see 3.1 above 
4. Risks and clinical benefits of the investigational device and 
clinical investigation 
4.1. 
Expected clinical benefits 

 
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The novel strategy of DSD might have a higher probability of terminating VT/VF and restoring 
spontaneous circulation. Based on the results from one major previous trial, there is a strong 
signal that DSD is superior to continuous standard defibrillation in refractory VT/VF in terms 
of saving more lives and neurological recovery. The clinical situation, to be in a cardiac 
arrest, is highly time critical, and every minute that passes without restoration of spontaneous 
circulation is associated with lower survival. Every minute in delay without defibrillation and 
CPR raise mortality by 10%. Part of this outcome is due to irreversible brain damage that is 
caused by cerebral hypoperfusion during the cardiac arrest. The earlier VT/VF can be 
terminated, and spontaneous circulation be restored, the higher the probability of survival. 
 
We therefore believe that a DSD strategy a soon as possible has a high potential to save 
more lives through a dual effect since: 
a) A larger proportion of patients will have their VT/VF terminated and spontaneous 
circulation restored, e.g. higher survival,  
b) The termination of VT/VF could occur sooner, leading to shorter duration of brain 
hypoperfusion and ischemia, and eventually better neurological function among survivors. 
4.2. 
Anticipated adverse device effects 
 
Possible adverse device effects with DSD compared to standard defibrillation include: 
 
1. Higher energy delivery 
A DSD strategy delivers double the amount of energy with each defibrillation. This may result 
in injuries such as superficial burns to the skin. 
 
2. Failure to deliver energy during defibrillation / or defibrillation malfunction 
There may be a theoretical risk of potential damage to defibrillators due to no synchronised 
shocks.[13] There is a theoretical risk that synchronised defibrillation could lead to high 
voltage and cause damage to the defibrillators. This risk may be higher if the defibrillator 
pads from the two defibrillators are placed linearly, as opposed to a 90-degree angle, and if 
defibrillation is synchronised. In this trial, the second pair of defibrillation electrodes will be 
placed at an almost 90-degree angle and defibrillation will be performed sequentially, 
meaning approximately a one second delay between defibrillation using the two defibrillators, 
with one person pressing both defibrillators in sequence. In the trial by Cheskes et al., there 
were no reports of defibrillation malfunction despite more than 130 patients treated using 
DSD. Also, in a recent survey on defibrillator damage during DSD use in clinical practice, the 
rate of defibrillator damage seemed to be exceedingly low.[14] In our pilot trial, there was no 
report of defibrillation malfunction or deficiencies, see above.  
 
4.3. 
Risks associated with participation in the clinical investigation 
 
The application of the second pair of defibrillation electrodes is associated with a short 
interruption in chest compression at the moment of placement of the posterior electrode. 
Long interruptions in chest compressions have been found to be associated with poorer 
outcome. However, short interruptions for ventilation have not been found to be worse than 
continuous chest compressions. In the trial by Cheskes et al., the application of the posterior 

 
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electrode was done in a standardised way, using the interruption in chest compressions for 
ventilation and simultaneously move the patient and apply the posterior electrode. They 
could also report guideline compliant CPR quality regardless of the treatment strategy 
(standard, Vector Change or DSD).[15] In order to minimise this risk there will be mandatory 
training for all participating ambulance crew on how to synchronise posterior defibrillation 
electrode placement to pauses in ventilation. The extra moment should not take longer than 
10-15 seconds. 
 
4.4. 
Possible interactions with concomitant medical treatments 
 
This is strictly a defibrillator management/strategy trial, and no medication are involved. All 
other medical treatments, e.g., adrenalin, amiodarone, airway management and ventilation 
strategies and the use of mechanical CPR-devices follow standard routine for ALS. 
 
During the course of the trial, it is possible that two other RCTs from ARREST (the 
Netherlands) are initiated in the same study region as this study. If the study period of these 
two other RCTs (REVIVE-PEEP and LUCASVP) would overlap with the current study, 
patients might be included in several RCTs simultaneously. Because neither of the selection, 
randomisation or treatment procedures interact with/influence each other’s selection, this 
would not influence or bias any of these studies’ results.  
 
4.5. 
Steps to be taken to control or mitigate risks 
 
1. Ambulance crew training. As mentioned above, the main risk with the DSD strategy, as far 
as we know, relates to the application of defibrillation electrodes and defibrillation. Therefore, 
all participating ambulance units must be trained and certified before participation in the trial. 
This is to minimise the risk of long interruptions in chest compressions and ensure correct 
electrode placement. 
 
2. During the pilot study, we had individual assessment and early feed-back of EMS 
intervention for every included patient to allow for early detection of unanticipated adverse 
events. In the main trial we will continue to have close monitoring, with early assessment and 
feedback with regular intervals, or if requested by EMS personnel in CRF1. Please also see 
the attached monitoring plan.  
 
3. Evaluation of defibrillators after each and every use. The Corpuls3 performs a complete 
system check each time it is switched on. This internal automatic self-test checks the system 
components. LIFEPAK 15 performs an internal self-test every time it is switched on and an 
automatic self-test daily at 03:00 AM.  
 
If error messages appear during automatic self-test, these are displayed in the 
status line and listed in the event history. After each use of DSD, the defibrillators will be 
checked for malfunction by performing an automatic self-test to ensure functionality. 
Furthermore, all Corpuls3 defibrillators used in the study will be tested by using a test box 
and performing a test discharge at least once weekly during the study period (part of current 

 
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routine) and as soon as possible after each DSD use, and a “User Test” as described in the 
operating instructions for LIFEPAK15.  
 
4. Stepwise escalation of including sites to uncover unknown risks. In order to perform 
monitoring of included patients and feedback from participating ambulance crew the trial will 
have an escalation strategy. The training protocol can be modified during trial to mitigate 
potential risks. For all significant modifications, the Swedish Medical Product Agency and the 
Swedish Ethical Review Authority will be notified. Please see also 9. Amendments to CIP.  
 
4.6. 
Rationale for benefit-risk ratio 
 
Cardiac arrest is a highly critical medical emergency. Only approximately 1/3 of all patients 
with VT/VF will survive to 30 days with standard ACLS treatment. Patients that survive the 
initial resuscitation phase and are transferred to hospital may still suffer from anoxic brain 
injury, cardiogenic shock, multiorgan failure and traumatic injuries from chest compressions. 
It is therefore highly important to convert patients in VF/VT to a sustained spontaneous 
circulation as soon as possible.  
 
In cardiac arrest situation with VT/VF, early defibrillation within 3-5 minutes is the most 
important therapeutic treatment to terminate the arrythmia and based on the results from 
previous trials there is a strong signal that DSD is superior to standard defibrillation in 
refractory VT/VF. In terms of survival. The risk with DSD includes a theoretical risk of 
defibrillation damage but this risk appears to be exceedingly low. Another physical risk is 
worse CPR quality. However, to be in a cardiac arrest is highly time critical, and every minute 
that passes without restoration of spontaneous circulation is associated with lower survival. 
Part of this is due to irreversible brain damage that is caused by cerebral hypoperfusion 
during the cardiac arrest. The earlier VT/VF can be terminated, and spontaneous circulation 
be restored, the higher the probability of survival. We believe that a DSD strategy a soon as 
possible can have a potential dual positive effect since  
 
a) a larger proportion of patients will have their VT/VF terminated and spontaneous 
circulation restored, which could potentially lead to higher survival,  
 
b) the termination of VT/VF will occur sooner, leading to shorter duration of brain 
hypoperfusion and ischemia, which could potentially lead to better neurological function 
among survivors. 
 
In summary, we believe that this novel method to use defibrillators has a strong potential 
benefit that largely outweighs the potential risks, and that the intervention can have a direct 
positive effect on the study participants. The net benefit is likely to be determined by efficacy 
of the intervention rather than safety aspects. 
 
5. Objectives and hypotheses of the clinical investigation 
5.1. 
Objectives 

 
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Primary objective 
To compare 30-day survival with early double sequential defibrillation in OHCA patients with 
initial shockable rhythm, at least one defibrillation performed and ongoing CPR, to standard 
defibrillation. 
 
 
Secondary objective(s) 
To compare the proportion of ROSC, survival to hospital admission, survival to hospital 
discharge with favourable neurological function and long-term survival with a strategy of early 
double sequential defibrillation, compared to standard defibrillation.  
 
Safety objectives 
 
To assess safety of an early DSD strategy in terms and defibrillation performance. 
5.2. 
Hypotheses 
 
Primary hypothesis 
 
In OHCA patients with an initial shockable rhythm who have undergone at least one 
defibrillation and still require CPR, switching to an early DSD strategy leads to higher 30-day 
survival rates compared to standard defibrillation.  
6. Design of the clinical investigation 
6.1. 
General information 
 
Design: This is an academic, investigator initiated, open-label randomised controlled trial 
(RCT) design and 1:1 allocation (1 DSD: 1 standard). Screening for inclusion will be 
performed in all cardiac arrests by participating EMS units where there are two study-specific 
defibrillators available on site: one Corpuls3 + one Corpuls3 OR one LIFEPAK15 + one 
LIFEPAK15 
Study population: All adult OHCA patients (>18 years) with VT/VF at initial rhythm analysis 
and at least one defibrillation performed in standard A-L position and ongoing CPR (no 
ROSC). 
Study setting: The study is conducted in the prehospital emergency medical services, i.e. 
ambulance organisations. The trial will be conducted by participating ambulance units 
attending OHCAs staffed with special nurses. These units will perform screening for 
inclusion, randomisation, intervention or control treatment and initial follow-up. All ambulance 
units in Sweden, the Netherlands and Spain follow the European Resuscitation Council 
(ERC) guidelines, published in 2021 and 2025 [7], and perform team training on an annual 
basis for high quality provision of ALS care in OHCA.  

 
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6.2. 
Endpoints 
6.2.1. 
Primary endpoints 
The primary endpoint of this trial will be survival to 30 days after the cardiac arrest.  
6.2.2. 
Key secondary endpoint (s) 
The secondary endpoints will, in chronological order be: 
 - Any prehospital ROSC, defined as confirmed ROSC by EMS personnel, in accordance 
with latest Utstein definition [16]  
- Survival to hospital Admission, defined as a patient admitted alive to a hospital ward 
(ICU or CCU unit) with spontaneous circulation  
- Survival to hospital discharge 
- Neurological function at hospital discharge (mRS) using the modified Rankin Scale 
(mRS) scale.[17]  
6.2.3. 
Other endpoints (optional) 
- Neurological function (CPC) at hospital discharge 
- Survival at 90 days 
- Neurological function (mRS and CPC) at 30 days 
- Neurological function (mRS and CPC) and Health-related Quality of Life at 90 days 
- Neurological function (mRS and CPC) and Health-related Quality of Life at 180 days 
- Termination of shockable rhythm, defined as the presence as a non-shockable rhythm 5 
seconds after defibrillation 
- Total time in ventricular fibrillation 
- Total number of shocks (each DSD or STD count as one) 
- Time from shock to re-fibrillation and time to first organised rhythm  
- Time to first ROSC 
- CPR quality measures (chest compression fraction, longest pause, chest compression 
depth) 
 
Data to assess the listed other endpoints above, such as long-term survival, Health-related 
Quality of Life and ECG-outcomes for mechanistic and explanatory sub studies are not 
mandatory to collect at all participating sites (optional).  
 
 
6.2.4. 
Description of the intervention and comparator 
 
Please see 6.6. 
 
6.3. 
Subjects 
6.3.1. 
Inclusion criteria 

 
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- OHCA patients in VT/VF at initial rhythm analysis, and at least one defibrillation performed 
in standard (A-L) position and still ongoing CPR. 
6.3.2. 
Exclusion criteria 
- Age < 18 years  
- Obvious pregnancy 
- Known preexisting Do Not Attempt Resuscitation order 
 
6.3.3. 
Investigation population 
 
The goal is to include 916 patients (458 in each group) 
6.3.4. 
Criteria and procedures for subject withdrawal or 
discontinuation. 
 
If DSD by any reasons cannot be performed due to any expected/unexpected circumstances 
at the scene EMS shall at once proceed with standard defibrillation according to routine 
practice. All randomised patients will be included in the intention to treat ITT analysis.  
6.4. 
Methods to minimise bias 
Study participants will be randomised at the individual patient level, therefore minimising 
confounding and allocation bias. 
 
Due to the nature of the intervention, blinding is not possible for providers, therefore there is 
a theoretical risk for performance bias (duration of CPR). Neurological and HRQoL follow-up 
at 90 and 180 days will be collected by research staff in a blinded way.  
6.5. 
Unblinding  
 
This is an open-label trial. However, the neurological long-term follow-up will be performed in 
a blinded way. The persons collecting the neurological follow-up data at 90 and 180 days will 
not be aware of the randomised allocation.  
6.6. 
Description of the clinical procedures and diagnostic methods 
relating to the clinical investigation  
 
The study will be conducted by prehospital emergency medical services, i.e. ambulance 
organisations. The trial will be conducted by participating ambulance units attending OHCAs. 
These units will perform screening for inclusion, randomisation, intervention or control 
treatment and initial follow-up. All ambulance units in Sweden, the Netherlands and Spain 
follow European resuscitation council (ERC) guidelines [18] and perform team training on an 
annual basis for high quality provision of ALS care in OHCA.  

 
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In clinical practice, a cardiac arrest is confirmed by the absence of consciousness and 
absence of normal or no breathing. In this clinical situation cardiac arrest shall be suspected 
and CPR initiated. In all cases of OHCA a defibrillator should always be attached with the 
standard pad placement first (A-L position) in accordance with standard of care and ERC 
guidelines. If there is VT/VF or an AED suggests defibrillation, defibrillation should be 
performed, and immediate chest compressions resumed.  
 
Thereafter, the patient can be screened for inclusion. If two study specific defibrillators are on 
site, and no exclusion criteria is present the patient can be included and randomised. 
Randomisation will be performed by opening an opaque envelope with concealed allocation 
that will be stored with the EMS defibrillators. All envelopes will be pre-randomised in a 1:1 
ratio in blocks consisting of 4-6-8 and stratified by region and ambulance provider. 
 
Defibrillator requirements:  
In this study all participating EMS units will have Corpuls3 or LIFEPAK15 defibrillators.  
A prerequisite for inclusion in this trial is that there are two study specific defibrillators on site; 
this means that either one EMS unit with two defibrillators (Corpuls3 or LIFEPAK15) or two 
EMS units with one device each shall be on site.  
In situations where the first EMS unit only has one defibrillator, but a second EMS unit 
arrives, the patient can still be included as soon as the second defibrillator is on site. 
Therefore, in clinical practice the inclusion of patients will follow the flow-chart below.  
If there is another defibrillator attached to the patient at EMS arrival (a public access AED or 
an AED from firefighters or police), that AED will be removed and the electrodes from 
Corpuls3 or LIFEPAK15 will be attached to the patient and connected to Corpuls3 or 
LIFEPAK15 in all cases (in accordance with routine practice). 
Intervention 
If the patient is randomised to the intervention group, the ambulance crew team will apply the 
second defibrillator with electrodes placed in the A-P position as soon as possible in the next 
CPR cycle (2 minutes) while trying to minimise interruptions in chest compressions. 
Defibrillation is performed by one person defibrillating both defibrillators in a sequential 
manner “Double Sequential Defibrillation” (DSD). All consecutive defibrillations will thereafter 
be performed with the DSD strategy until ROSC, termination of resuscitation or decision to 
move the patient to hospital. See also 2.2.2 Intervention group. 
 
Control 
If randomised to the control group, the ambulance crew team will continue ACLS in 
accordance with standard of care. Defibrillation is performed with standard electrode 
placement using a single defibrillator. If an AED is the first defibrillator attached to the patient, 
the ambulance crew should shift from an AED to their own manual defibrillator, but the mode 
of defibrillation should follow standard treatment in A-L position and only one defibrillation 
from one defibrillator should be used for each defibrillation attempt, and continued until 
ROSC, termination of resuscitation or decision to move the patient to hospital. Due to the 

 
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updated European guidelines in 2025, it lies within the decision capacity of each EMS unit to 
shift from A-L to A-P after three failed defibrillations. See also 2.2.3 Control group  
 
 
OHCA = Out-of-Hospital Cardiac Arrest, VT/VF = pulseless Ventricular Tachycardia/Ventricular 
Fibrillation, CPR = Cardiopulmonary Resuscitation, DSD = Double Sequential Defibrillation, CRF = 
Clinical Report Form 
 
 
Follow-up will be performed immediately after every resuscitation attempt (patient 
characteristics, pre-hospital treatment and short-term outcome and defibrillator files), at the 
hospital and long term follow up until 180 days. For details regarding data collection, se 
section 8. 
 

 
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6.7 Participating Trial sites  
 
Sweden 
 
1. Emergency medical services Sahlgrenska Universitetssjukhuset, Region Västra Götaland 
Gullbergs Strandsgata 36C 
411 04 Gothenburg  
Phone: 0721-876236  
Local PI: Carl Magnusson, R.N., Ph.D. Head of Research and Development 
 
2. Emergency medical services Sjukhusen I Väster, Region Västra Götaland (Alingsås/Lerum 
and Kungälv)  
Södra Ringgatan 30 
441 83 Alingsås  
Phone: 03232-22 60 00  
Local PI: Andreas Claesson, R.N. Ph.D.  
 
3. Emergency medical services Region Halland 
Ambulans och Sjukresor I Halland (ASH) Skånegatan 59, plan 3 
30238 Halmstad 
Phone (+46) 076 72 14 007 
Local PI: Kristoffer Wibring, R.N. Ph.D.  
4. Emergency medical services Skaraborgs Sjukhus, Region Västra Götaland 
Lövängsvägen 1,  
54949 Skövde 
Phone: 0500 - 43 10 00 
Local PI: Per Wennberg, R.N. Ph.D. 
 
5. Emergency medical services NU-Sjukvården, Region Västra Götaland 
Område ledning och stöd, NU-sjukvården 
461 85 Trollhättan 
Phone: 010-435 10 35 
Local PI: Carl Magnusson, R.N. Ph.D. 
 
6. Emergency medical services, Region Värmland 
Älvgatan 39,  
65230 Karlstad 
Phone: 010-831 50 00 
Local PI: Linus Lilja, M.D., Ph.D. 
 
7. Emergency medical services, Södra Älvsborgs Sjukhus, Region Västra Götaland 
Brämhultsvägen 53,  
501 82 Borås 
Phone: 033 - 616 10 00  
Local PI Emil Bergerum, R.N. 
 

 
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8. Emergency medical services, Prehospital Intensive Care Unit Shalgrenska 
universitetssjukhuset / Östra Sjukhuset 
Diagnosvägen 11 
41 650 Göteborg 
Phone: 031 - 343 40 43 
Local PI: Patrik Martner., M.D.  
9. Ambulanshelikoptern (HEMS) Västra Götalandsregionen, Kungälvs sjukhus 
Lasarettsgatan 1 
442 83 KUNGÄLV 
Phone: 0046 (31) 55 63 85 
Local PI: Knut Taxbro, M.D. Ph.D. 
The Netherlands 
10. ARREST (AmsteRdam REsuscitation STudies), Amsterdam UMC  
Local PI: Christian Van der Werf M.D. Ph.D. 
Adress: Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands 
Phone: (+31) 6 14425804 
Mail: c.vanderwerf@amsterdamumc.nl 
Spain 
11. SUMMA 112, Madrid 
Local PI: Carlos Rubio Chacón 
C. de la Antracita, 2 Bis, Arganzuela, 28045 Madrid 
Mail: carlos.rubio@salud.madrid.org 
Phone: (+34) 639 91 74 03 
Local PI: Carlos Rubio Chacón M.D. Ph.D. 
 
12. Centro de Emergencias 061 Andalucía,  
Servicio Andaluz de Salud 
Avda Severo Ochoa 28,  
29560, Parque Tecnológico de Andalucía, Campanillas, Málaga 
Phone: (+34) 617 56 33 52 
Local PI: María José Luque-Hernández M.D. Ph.D. 
 
13. Sistema de Emergencias Mediques (EMS) de Catalunya 
Pablo Iglesias, 101-115 08908 L'Hospitalet de Llobregat  
Phone. (+34) 93 264 44 00 Ext. 12200 | Mòbil 616446068 
Local PI: Dr. Xavier Jiménez Fàbrega, MD, PhD 
14. Médico Emergencias Osakidetza EMERGENTZIAK, (Bilbao) 
Maria Diaz de Haro 53, 48004 Bilbao 
Baque Country. Spain 
Phone: (+34) 99 68 11 82 
Local PI, Cristian Fernández Barreras MD  
 

 
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Addition of new sites during the course of the clinical trial:  
Additional sites can and will be added during the course of the clinical investigation. Before 
any addition of new sites approval must be sought by from relevant authorities, i.e., 
application of substantial modification to the Swedish medical product agency and Swedish 
ethical review authority, regarding new sites, must be approved.  
6.8. End of the clinical investigation 
 
The clinical investigation ends when the last subject has completed the last follow-up at 180 
days. The sponsor will notify the Swedish Medical Products Agency within 15 days after the 
end of the clinical investigation and send the clinical investigation report within 1 year after 
the end of the clinical investigation, including an easily understandable summary.  
6.9. Monitoring plan 
 
The clinical investigation will be monitored by a monitor during the clinical investigation, and 
after the clinical investigation has been completed, so as to ensure that the clinical 
investigation is carried out according to the CIP, and that data is collected, documented, and 
reported according to SS-EN ISO 14155:2020 and applicable ethical and regulatory 
requirements. Monitoring is performed as per the investigation’s monitoring plan and is 
intended to ensure that the subject’s rights, safety, and wellbeing are met as well as data in 
the CRF are complete, correct, and consistent with the source data. 
 
Please see appendix monitoring plan: “Monitoring plan DoubleD V. 250820-signed” 
 
7. Statistical considerations. 
7.1. 
Analysis population  
 
The principal analysis strategy will be on an “intention to treat” (ITT) basis. All randomised 
patients who fulfilled inclusion criteria and no exclusion criteria will be included in this 
analysis. We will call this population ITT. 
The modified intention to treat population mITT is defined as all patients in the ITT population 
that had shockable rhythm at any rhythm analysis after randomisation. In other words, the 
subgroup of ITT patients that are amendable to interventional or standard defibrillation. This 
will be defined as patients that received any kind of defibrillation after randomisation.  
The per-protocol population is defined as the subset of the mITT population that received 
defibrillation according to allocated treatment.  
  
 
 

 
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Consort flow diagram  
 
 
 
7.2. 
Descriptive statistics 
Descriptive statistics will be presented as counts and proportions for categorial variables. For 
continuous variables the mean, standard deviation, medial and quartiles (Q1, Q3) will be 
presented. Balance between the treatment groups will be assessed using the standardised 
mean difference.  
7.3. 
Analytical procedures  

 
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All primary analyses will be conducted on an intention-to-treat basis (ITT). The patient will be 
analysed based on their group allocation. 
Secondary analyses will be performed on: 
- 
Modified intention-to-treat (mITT)  
- 
Per protocol (PP)  
Primary outcome 
- Survival to 30-days 
Secondary outcome 
- Neurological function (mRS) at hospital discharge 
- Survival to hospital admission 
- Any ROSC 
Null-hypothesis significance testing for the primary outcome and the secondary outcomes of 
neurological function at discharge, survival to hospital admission and ROSC will be 
performed. Analyses will be conducted using logistic regression. The rationale behind this is 
to adjust for baseline characteristics to potentially increase power. 
Adjustment for baseline characteristics  
To increase power, we will adjust all outcome comparisons for strong prognostic factors. 
These will include number of defibrillations performed prior to randomisation, age and sex. 
7.4. 
Sample size calculation  
 
Baseline 30-day survival is based on data from the Swedish Register for Cardiopulmonary 
Resuscitation (SRCR). Among patients with shockable rhythm and > 1 defibrillation attempts, 
the 30-day survival was ~ 25%. We estimate that the survival rate could reach 33.5% in the 
intervention group (RR=1.34). The estimates are derived from the current survival SRCR (9) 
and the relative effect size in the Canadian trial (RR 2.21). However, we chose a more 
conservative relative risk. 
With an alpha level of 0.05 and a beta level of 0.2, the estimated sample size would be 898 
patients without interim analyses. The trial will have an adaptive parallel sequential design with 
interim-analysis and an independent data safety and monitoring board, with a priori stopping 
criteria for efficacy or harm but not for futility. 
To adjust p-values for multiple looks, we use Lan and DeMets alpha-spending approximation of 
the O’Brien-Flemming boundaries. 
Interim analyses will be conducted at different information rates (i.e. percentage of patients 
included in the study). Planned analyses are at 25% of included cases (229 patients), 50% of 
included cases (458 patients) and at 75% of included cases (686 patients). Critical values for 
superiority on the P-value scale are the following: 

 
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25%: 229: 0.00001 
50%: 458: 0.00305 
75%: 686: 0.01832 
The P-value threshold for the final analysis (100%, 915 patients) is 0.044 
7.5. 
Missing data 
The aim is to minimise the missing data on core variables (treatment group, outcomes, 
number of defibrillations, age and sex). If some important data cannot be collected, we will 
consider using multiple imputation. The method will be multiple imputation with chained 
equations (mice). We assume that the missing will be at random (MAR).  
7.6. 
Exploratory analysis and sensitivity analysis  
The primary analysis will follow a frequentist approach, incorporating pre-specified interim 
analyses with appropriate alpha-spending adjustments to control the overall Type I error rate. 
These adjustments are necessary to ensure statistical rigor and regulatory compliance when 
conducting multiple looks at the data. 
To aid in the interpretation of the primary and key secondary endpoints, a Bayesian analysis 
will be conducted to provide an additional probabilistic perspective on treatment effects, both 
in the overall study population and in relevant subgroups. This Bayesian approach allows for 
evaluating the probability of treatment benefits without requiring adjustments for multiple 
testing. The Bayesian analyses will use a conservative prior of normal (0, 0.5) on the log-
odds scale and assume equal change of benefit and harm a priori. 
The Bayesian analysis is intended to serve as a complementary assessment to the primary 
frequentist inference. A dedicated manuscript will report the Bayesian findings separately. 
The posterior probability distributions will be illustrated graphically, and the probability that 
the true treatment effect is larger than or within various thresholds (e.g., risk ratio above 1.0) 
will be provided. Exploratory sub-group analyses will be conducted on patients with a 
witnessed cardiac arrest, patient receiving bystander cardiopulmonary resuscitation, time to 
first defibrillation (below/above median) and stratified by age, sex and site. 
Sub-studies: 
Further sub-studies are planned to compare treatment effect in relation to subgroup exposure 
such as; a) EMS response time, b) if VF is refractory or recurrent, c) number of shocks 
before randomisation, d) AMSA, e) peri-shock pause, f) cause of cardiac arrest (cardiac / 
non-cardiac, STEMI / non-STEMI) and), g) chest compression fraction and h) Longitudinal 
follow up of neurological function and HRQoL. Other pre-specified sub studies may be added 
to this list during the course of the trial. 
7.7. 
 Data safety monitoring board (DSMB) 

 
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An independent data safety monitoring committee will be assigned by the steering group. An 
independent statistician will conduct the interim analyses. The data safety monitoring 
committee can recommend stopping or pause the trial if: 
 
Superiority 
Critical values for superiority are reached: 
25%: 229: 0.00001 
50%: 458: 0.00305 
75%: 686: 0.01832 
 
Harm 
If the interim analysis shows a significant increase in risk (e.g., mortality) in the treatment arm 
compared to control, with p ≤ 0.05, the monitoring committee shall recommend stopping the 
trial for harm.  
 
The advice(s) of the DSMB will only be sent to the sponsor of the study. Should the sponsor 
decide not to fully implement the advice of the DSMB, the sponsor will send the advice to the 
review committee, including a note to substantiate why (part of) the advice of the DSMB will 
not be followed. 
 
7.8. 
Reporting deviations 
If deviations from the statistical analysis plan occur, we will present and explain these 
changes in the methods section of the paper. 
7.9. 
Handling of imbalance of subjects per site 
As each trial site have their own stratified randomisation list each site will have a balance of 
patients randomised to both groups. 
8. Data management and protection 
 
Subjects who participate in the clinical investigation will be coded with a specific clinical 
investigation identification number. All subjects will be registered in a subject identification list 
(subject enrolment and identification list) that connects the subject’s name and personal 
number with a clinical investigation identification number. 
All data will be registered, managed, and stored in a manner that enables correct reporting, 
interpretation, and verification.  
8.1. 
Data collection and Case Report Forms 
 
Follow-up and data collection will be performed in three different and separate 
levels/occasions. All key primary data will be collected in all participating sites. The exact 

 
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methods for data collection and origin of source data may vary between sites in different 
participating countries and will be described in detail in the separate national applications.  
 
A. For all patients after finished resuscitation:  
- Prehospital Digital CRF 1 (see below)  
- Ambulance charts, pre-hospital treatment, patient characteristics and short-term outcome 
- ECG files from defibrillators used by including ambulance unit  
- Time delays for EMS emergency dispatch (In Sweden, from the Swedish emergency 
dispatch organisation SOS-Alarm) 
 
B. For all patients surviving to hospital admission: 
- In-hospital treatment, survival to discharge and date of discharge 
- For patients undergoing angiography, variables from the Swedish Coronary Angiography 
and angioplasty register, SCAAR (Sweden only) 
- Medical charts, length of stay in hospital, if coronary angiography or ECMO was performed, 
date of discharge and ICD-codes at discharge (CRF 2) 
 
C. All patients surviving to hospital discharge 
- Neurological function (mRS and CPC) at hospital discharge 
 
D. All patients surviving to 30 days 
- Survival to 30 days,  
 
E. For patients surviving to 30, 90 and 180 days (optional): 
- Neurological function at 30 days (mRS and CPC) 
- Survival to 90 days 
- Neurological function (mRS, CPC), self-reported cognitive function (Single item) and 
Health-related quality of life (EQ-5D-5L, EQ VAS, PHQ-9, GAD, LiSAT-11, MFIS-21) at 90 
days 
- Survival to 180 days 
- Neurological function (mRS, CPC), self-reported cognitive function (Single item) and 
Health-related quality of life (EQ-5D-5L, EQ VAS, PHQ-9, GAD, LiSAT-11, MFIS-21) at 180 
days 
8.1.1 Prehospital CRF1, Characteristics during the resuscitation phase  
After completing the care of the patient, the study-responsible EMS unit will report a digital 
prehospital CRF. This is practically done by using and reading a study specific QR-code 
located on the back of the specific randomisation envelope/sheet using a smart-phone. This 
will open a webpage link to REDCap, automatic registration of time of registration and 
information to be filled in when opened.  
The prehospital CRF will contain basic on-site information such as which ambulance that 
performed randomisation, randomisation study number, time and date of cardiac arrest, 
number of shocks prior to EMS arrival and number of shocks prior to randomisation, 
treatment allocation, if DSD was performed and number of DSD shock, estimated weight of 
patient, ROSC, if the patients survived the event and to what hospital the patients was 

 
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transferred. Furthermore, if the patient has a known identity, personal identification number 
will be included to enable follow-up. If the patients do not have a known identity, a temporary 
identification number will be used.  
The prehospital CRF allows for real-time monitoring of randomisation and allows for early 
start of follow-up. If CRF1 is incomplete, missing variables can be collected from the 
ambulance charts. 
Other core resuscitation characteristics will later be collected from ambulance medical charts 
and/or cardiac arrest registers. This data is standard and mandatory for all EMS personal to 
report and contains resuscitation and patient characteristics and is part of routine 
documentation. 
ECG files from defibrillators. All data stored in the defibrillators after each use in the trial will 
be exported to a secure server and analysed for type of cardiac rhythms during resuscitation, 
type of defibrillation performed, result of defibrillation on cardiac rhythm as well as 
defibrillation safety.  
For EMS units that use CPR quality feedback devices in their routine practice, information 
from those devices will be collected in the same way as ECG-files. All data above will be 
collected continuously during the course of the clinical trial and entered in the central 
REDCap database at Karolinska Institutet. 
All key data will be collected in all participating sites but there may be national variations in 
the process of collecting data. Details regarding the data collection methods will be described 
in the applications (including ethics applications) of the different countries.  
8.1.2 In-hospital CRF in-hospital treatment 
The in-hospital CRF will cover core in-hospital treatment. The in-hospital CRF will collect 
core data such as length of stay, survival to hospital discharge, date of discharge, if coronary 
angiography was performed, target temperature management, if the patients received 
treatment with ECMO, and neurological function (mRS and CPC) at discharge. In addition, 
the mandatory SRCR part 2 will also be collected in Sweden. Neurological assessment at 
discharge can be performed either by research nurses at the hospital or the neurological 
follow-up team or by an assessment of medical charts (see below). 
Please see supplemental file intrahospital CRF. 
In Sweden, for the subset of patients that undergo coronary angiography, core variables 
regarding coronary anatomy, number of vessels with significant atherosclerotic stenosis and 
coronary intervention will be collected from the Swedish Coronary Angiography and 
angioplasty register (SCAAR). 
8.1.3 Neurological and patient-reported follow-up at discharge, 30, 90 and 180 
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For patients who survive to hospital discharge and have signed an informed consent to 
further participation in the trial, a specific follow-up team, separated and blinded from the 
care and randomised allocation (intervention or control) will be responsible for neurological 
follow-up. Neurological function at hospital discharge will be assessed either by review of 
hospital charts or telephone follow-up. Neurological function will be assessed according to 
the modified Ranking Scale (mRS) and the Cerebral Performance Category (CPC) scale at 
hospital discharge, 30, 90 and 180 days.  
The mRS scale includes categories 1-6, where higher numbers indicate more severe 
disability:  
0 = no symptoms,  
1 = no significant disability—able to carry out all usual activities, despite some symptoms, 
2 = slight disability—able to look after own affairs without assistance but unable to carry out 
all previous activities, 
3 = moderate disability—requires some help but able to walk unassisted,  
4 = moderately severe disability—unable to attend to own bodily needs without assistance 
and/or unable to walk unassisted, 
5 = severe disability—requires constant nursing care and attention, bedridden, incontinent, 
and 
6 = dead.  
 
The CPC scale includes categories 1-5, where higher numbers indicate more severe 
neurological impairment: 
1 = Conscious, alert, able to work and lead a normal life. May have minor psychologic or 
neurologic deficits (mild dysphasia, non-incapacitating hemiparesis, or minor cranial nerve 
abnormalities), 
2 = Conscious. Sufficient cerebral function for part-time work in sheltered environment or 
independent activities of daily life (dress, travel by public transportation, food preparation). 
May have hemiplegia, seizures, ataxia, dysarthria, or permanent memory or mental changes, 
3 = Conscious. Dependent on others for daily support (in an institution or at home with 
exceptional family effort). Has at least limited cognition. This category includes a wide range 
of cerebral abnormalities, from patients who are ambulatory but have severe memory 
disturbances or dementia precluding independent existence, to those who are paralyzed and 
can communicate only with their eyes, as in the “locked in” syndrome,  
4 = Unconscious. Unaware of surroundings, no cognition. No verbal and/or psychologic 
interaction with environment, and 
5 = Brain dead, circulation preserved. Death at discharge.  
 
Patients that are alive at 90 and 180 days will also be evaluated for cognitive function and 
HRQoL using the self-reporting measures described below.  
The single item for self-reported cognitive function is developed and used by the SRCR. It is 
formulated “How do you perceive your memory-, concentration- and/or planning ability today 
compared to before your cardiac arrest?”. The responses are rated on a five-point scale from 
“It is much better” to “It is much worse”.  

 
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The EuroQol 5D 5L (EQ-5D-5L) consists of 5 health domains (mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a five-point 
scale, ranging from 1 “no problems” to 5 “extreme problems”.  
The EQ VAS is a single item measure evaluating “your health today”, using a visual analogue 
scale from 0 (“worst possible health”) to 100 (“best possible health”).  
The 11-item Life Satisfaction questionnaire (LiSat-11) consists of 11 single items, one 
representing overall satisfaction with life (life as a whole) and 10 addressing specific domains 
of life satisfaction (vocation, economy, leisure, friends, sexual-life, self-care, family-life, 
partner relation, physical health, and psychological health). Each domain is assessed on a 
six-point scale ranging from “Very dissatisfied” to “Very satisfied”. 
The Patient Health Questionnaire (PHQ-9) is a screening measure for symptoms of 
depression. It consists of 9 (+1) items with responses rated on a four-point scale from 0 “not 
at all” to 3 “nearly every day”. The item scores are summarised to a total score from 0-27, 
with higher scores indicating a more probable presence of depression. The last question 
addresses the possible impact on daily activities.  
The Generalised Anxiety Disorder 7-item scale (GAD-7) is a screening measure for 
symptoms of anxiety. It consists of 7 (+1) items with responses rated on a four-point scale 
from 0 “not at all” to 3 “nearly every day”. The item scores are summarised to a total score 
from 0-21, with higher scores indicating a more probable presence of anxiety. The last 
question addresses the possible impact on daily activities. 
The Modified Fatigue Impact Scale (MFIS) is a measure of how fatigue impacts life related to 
the respondents physical, cognitive, and psychosocial functioning. The original scale consists 
of 21 items. Responses are rated on a five-point scale from “never” (0) to “almost always” (4), 
resulting in a total score (0-84) and three subscale scores. Higher scores indicate a greater 
impact of fatigue on a person’s activities.  
Variables from the neurological and HRQoL follow-up will be entered directly to a secure 
REDCap database at KI.  
8.2. 
Data storage 
All data reported from prehospital CRF, in-hospital CRF and neurological follow-up CRF will 
be digitally entered into a study-specific database (REDCap). The database will be stored on 
a secure server at the Karolinska Institute. 
All essential documentation and trial records will be stored at in conformance with the 
applicable regulatory requirements. Access to stored information will be restricted to 
authorised personnel. Data will be stored in a secure area with access restricted to staff 
working on the trial. Any data that are transferred out of the secure environment (for example 
for statistical analysis) will adhere to standard procedures for secure data management. 
All personal data will be handled according to the standard procedures for the current 
registries and medical records and in accordance with the General Data Protection 
Regulation (GDPR). Personal numbers and all other data that can lead to identification of 

 
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subjects included in the study will be coded and be accessible to key persons in the project 
to enable follow-up. The database will also only be accessible to key persons in the project. 
8.3. 
Archiving 
The PI and sponsor will maintain the essential clinical investigation documents in the 
investigation site files archive and sponsor files archive, respectively. The sponsor shall keep 
all documentation and data for at least 10 years after the clinical investigation has ended. 
The PI will archive all local investigation documentation for at least 10 years or as long as 
stipulated by the local institution. 
8.4. 
Data protection 
If any part of the data is handled by any other organisation, inside or outside the European 
Union, appropriate agreements and/or other documentation will be established, to ensure 
that the data processing is performed in accordance with the provisions of the General Data 
Protection Regulation (EU ordinance 2016/679, GDPR) and other relevant legislation, 
before any data transfer takes place. 
The content of the informed consent form shall comply with relevant integrity and data 
protection legislation. In the subject information and the informed consent form, the subject 
will be given complete information about how collection, use and publication of their clinical 
investigation data will take place. The subject information and the informed consent form will 
explain how clinical investigation data are stored to maintain confidentiality in accordance 
with national data legislation. 
The informed consent form will also explain that for verification of the data, authorised 
representatives of the sponsor, as well as relevant authority, may require access to parts of 
medical records or study records that are relevant to the clinical investigation, including the 
subject’s medical history. 
Measures in the event of a personal data breach in the Double-D trial  
1. Identify and document the incident  
- Assess whether personal data is involved (e.g., code keys, study data, personal ID 
numbers).  
- Document what happened, what data was affected, and the extent of the incident.  
2. Assess risk to data subjects  
- Analyse the potential risks: identity theft, discrimination, reputational harm, etc.  
- If low risk: document internally, no notification required.  
- If risk exists, proceed to steps 3 and 4.  
3. Notify the Swedish Authority for Privacy Protection (IMY) within 72 hours  
- Include a description of the incident, data affected, number of data subjects, contact 
information, and corrective actions.  
- Use IMY's online reporting service.  

 
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4. Notify affected data subjects if there is a high risk  
- Inform them without undue delay.  
- Explain what happened and provide protective advice.  
- Exception: e.g., if data was encrypted and risk is low.  
5. Take technical and organisational measures  
- Stop further data leakage.  
- Restrict access and update security measures.  
- Provide staff training if necessary.  
6. Inform the sponsor and responsible investigator  
- Notify according to protocol and contractual agreements.  
- The sponsor is often the data controller responsible for regulatory communication.  
9.  Amendments to the CIP 
Amendments to the CIP will be agreed upon between the coordinating investigator and the 
sponsor. Substantial modifications must be approved by the Swedish Ethical Review 
Authority and/or the Swedish Medical Products Agency before implementation. 
10. 
Deviations from the CIP 
Investigator(s) are not allowed to deviate from the CIP except if it is for the protection of the 
subject´s rights, safety, or well-being under emergency circumstances.  
All such deviations shall be documented and reported to the sponsor, the Swedish Medical 
Products Agency and/or the Swedish Ethical Review Authority (as applicable) as soon as 
possible. 
All deviations shall be documented with an explanation and reported to the sponsor. 
Deviations will be reviewed by the sponsor and reported to the appropriate regulatory bodies 
as required. 
11. 
Device traceability and accountability 
The investigational device(s) are part of the EMS standard equipment. The devices will only 
be used in the clinical investigation according to the clinical investigation plan. The sponsor 
provides the site with written instructions and training of DSD. 
12. 
Statements of compliance 
 
12.1. 
Compliance to the investigational plan, good clinical practice, 
and regulations 
 
The clinical investigation will be conducted in accordance with the clinical investigation plan, 
the ethical principles of the Declaration of Helsinki, the principles of SS-EN ISO 14155:2020 
and current national and international regulations governing this clinical investigation. This is 
to ensure the safety and integrity of the subjects as well as the quality of the data collected. 

 
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12.2. 
Ethical review of the clinical investigation 
 
The clinical investigation will commence when written approval/favourable opinion from the 
Swedish Ethical Review Authority has been received and confirmation of validity has been 
received from the Swedish Medical Products Agency. 
The final version of the informed consent form and other information provided to subjects, 
must be approved or given a written positive opinion by the Swedish Ethical Review Authority 
or the Swedish Medical Products Agency. The Swedish Ethical Review Authority and the 
Swedish Medical Products Agency must be informed of any changes in the CIP in 
accordance with the current requirements. For each participating site outside of Sweden, a 
written approval/favourable opinion must be received from national and/or local ethical review 
boards and applicable authorities.  
12.3. 
Insurance 
 
Swedish Patient Insurance (Patientskadeförsäkring): The Swedish healthcare regions have 
signed a patient insurance with Landstingens Ömsesidiga Försäkringsbolag, LÖF. 
Separate national insurance agreements will be arranged for participating sites outside of 
Sweden. 
 
13. 
Informed consent process 
13.1. 
General process for informed consent 
 
This study will be conducted according to the principles of the Declaration of Helsinki (version 
2024, date 22-10-2024, see for the most recent version: www.wma.net). Informed consent for 
participating in the study cannot be obtained from the subject at the scene since the victim is 
unconscious. The cardiac arrest may be witnessed by family members, but to ask for consent 
form a relative or a legally representative in this scenario is not possible for both practical and 
ethical reasons. The time window to include and perform the intervention is within minutes. 
Therefore, informed consent cannot be obtained before the trial intervention.  
 
According to the Helsinki Declaration paragraph 30; 
 “Research involving subjects who are physically or mentally incapable of giving consent, for 
example, unconscious patients, may be done only if the physical or mental condition that 
prevents giving informed consent is a necessary characteristic of the research group. In such 
circumstances the physician must seek informed consent from the legally authorizes 
representative. If no such representative is available and if the research cannot be delayed, 
the study may proceed without informed consent provided that the specific reasons for 
involving subjects with a condition that renders them unable to give informed consent have 
been stated in the research protocol and the study has been approved by a research ethics 
committee.” 

 
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According to MDR 2017/745 article 68, it possible to obtain informed consent to participate in 
a trial after the decision to include the patient if all other circumstances outlined in article 68 
are fulfilled: 
- The decision to include the patients is done in conjunction with the interventional treatment. 
The treatment in this trial must be provided during cardiopulmonary resuscitation, within 
minutes from the cardiac arrest.  
- It´s not possible to obtain consent prior to inclusion since cardiac arrest is a sudden and 
unexpected life-threatening emergency event. 
- There are scientific reasons to believe that participation in the trial can have direct clinical 
benefits for the participating patient/study subject. 
- There is no possibility to inform or obtain consent from a legally representative since the 
interventional treatment must be provided within minutes from EMS arrival and during 
ongoing CPR. 
- There is no way for the principal investigator to obtain information that the study subject has 
expressed an opposing view to participate in the trial beforehand, since cardiac arrest is a 
sudden, unexpected life-threatening emergency. 
- The trial intervention has a direct connection to the medical condition (cardiac arrest) that 
renders the patient/study subject unable to give informed consent.  
 
13.2. 
Consent process 
The probability of surviving cardiac arrest is very low; overall, 90% of the patients die. In the 
OHCA sub-set of patients with VT/VF, survival at 30 days is about 30%. In a cardiac arrest 
scenario, treatment of CPR and defibrillation must be started immediately to increase the 
chance of survival.  
Due to the nature of the condition of sudden cardiac arrest, informed consent for participating 
in the study cannot be obtained from the subject at the scene since the victim is unconscious 
at the time for study inclusion, and the EMS personnel or the sponsor has no previous 
information about the patients willing to participate in the study or not. The clinical course in 
patients that regains circulation after cardiac arrest shows a wide variety, from irreversible to 
reversible circulatory shock, and from irreversible brain damage and death to neurologically 
intact survival and fast recovery in cognitive functions. Therefore, the strategy for obtaining 
informed consent varies dependent on patient outcome. 
The strategy for obtaining informed consent is as follows according to the patient’s status  
1. The patient who is not regaining circulation and is declared dead at the scene of the 
arrest or in the emergency department. No consent will be obtained.  
2. The patient who survives the initial resuscitation phase, is transferred to hospital and 
is conscious and neurologically capable to provide informed consent. In Sweden, 
information about the study (both oral and written) will be given during hospital stay. 
The information includes the purpose of the study, the study intervention, possible 
risks and benefits from participating in the study and who is legal responsible for the 
study. In the information it is also clarified that all participation is voluntary, the right to 

 
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not participate in the study and the right to withdraw participation. The informed 
consent is obtained.  
3. The patient who survives but is not fully conscious, GCS <14, has severe dementia, 
suffers from expressive and/or impressive aphasia, or is unable to write his or her 
signature. In this case, when the patient is not able to give an informed consent by his 
or her own, the consent shall as soon as possible be sought after by a legally 
representative without undue delay. If the patient does not have a legally 
representative, and still is unable to provide informed consent due to cognitive 
impairment after the ICU period, a renewed attempt will be made to inform the patient 
and obtain informed consent as soon as the patient can give informed consent. 
Attempts to inform the patient and obtain consent for this category of patients will 
continue during the entire follow-up period (180 days). In patients who die or do not 
regain neurological function to provide informed consent during the follow-up period 
(180 days), no consent will be obtained. 
If informed consent has been obtained from the legally designated representative, informed 
consent to continue the participation in the clinical trial shall be obtained from the patient as 
soon as he or she can give informed consent.  
The informed consent process is performed by local staff at each referring hospital. 
There may be national variations in the process of informing the patient and obtaining 
informed consent. For details each participating site outside of Sweden, the informed consent 
process will follow national and local laws and regulations. 
The principal investigator shall ensure that the subject is given full and adequate oral and 
written information about the clinical investigation, its purpose, any risks and benefits as well 
as inclusion and exclusion criteria.  
Subjects must also be informed that they are free to discontinue their participation in the 
clinical investigation at any time without having to provide a reason. Subjects shall be given 
the opportunity to ask questions and be allowed time to consider the provided information 
and participation in the clinical investigation. If the person chooses to participate, both the 
subject and the investigator shall sign the informed consent form. A copy of the subject 
information as well as a copy of the informed consent form shall be provided to the subject.  
The process shall be documented in the subject’s source documents and the signed 
informed consents shall be maintained with the essential documents. If new information 
becomes available that can significantly affect a subject's future health and medical care, that 
information shall be provided to the affected subject(s) in written form. If new information is 
added to the clinical investigation, the subject has the right to reconsider whether they will 
continue their participation. In patients that don’t want to participate or withdraw a given 
consent, there will be no more follow-ups. All patient data collected up to this point will be 
deleted with the exception of anonymised data regarding defibrillator safety (device 
deficiencies/damages). 

 
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14. 
Adverse events, adverse device effects and device 
deficiencies 
14.1. 
Definitions 
 
Adverse Event 
An Adverse Event (AE) is untoward medical occurrence, unintended disease or injury or any 
untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other 
persons, in the context of a clinical investigation, whether or not related to the investigational 
device. 
This definition includes events that are anticipated as well as unanticipated events.  
This definition includes events occurring in the context of a clinical investigation related to the 
investigational device, the comparator or the procedures involved. 
 
Adverse Device Effect 
An Adverse Device Effect (ADE) is any AE related to the use of an investigational medical 
device. 
This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. This includes both the interventional and comparator. 
 
Serious Adverse Event 
A Serious Adverse Event (SAE) is any AE that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, that resulted in any of the following: 
i. life-threatening illness or injury, 
ii. permanent impairment of a body structure or a body function, 
iii. hospitalization or prolongation of patient hospitalization, 
iv. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
v. chronic disease, 
c) foetal distress, foetal death or a congenital physical or mental impairment or birth defect 
 
Serious Adverse Device Effect 
 
A Serious Adverse Device Effect (SADE) is an ADE that has resulted in any of the 
consequences characteristic of a serious adverse event. 
SAEs related to procedures imposed by the clinical investigation plan but not with the use of 
the device shall not be considered Serious Adverse Device Effects. 
 
Unanticipated Serious Adverse Device Effect 

 
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An Unanticipated SADE is an effect which by its nature, incidence, severity or outcome has 
not been identified in the current risk assessment. Procedures associated with the use of a 
device shall be addressed in the risk assessment, which makes it possible to determine 
whether the procedure related SAEs are Unanticipated Serious Adverse Device Effect or not. 
SAEs related to procedures imposed by the clinical investigation plan but not with the use of 
the device shall not be considered Serious Adverse Device Effects. 
For the anticipated adverse device effects, se section 4.2 above. 
 
Device Deficiency 
A Device Deficiency is any inadequacy in the identity, quality, durability, reliability, safety or 
performance of an investigational device, including malfunction, use errors or inadequacy in 
information supplied by the manufacturer.  
This includes detected errors at defibrillator self-test after each use. 
14.2. 
Recording and Reporting 
 
Recording 
As stated in section 13.3, cardiac arrest is associated with a probability of death of 70-80% in 
the first 30 days. Even among survivors this condition is associated with neurological, cardiac 
and multi-organ failure in the first post-cardiac arrest period. The standard treatment includes 
known side effects such as rib-cage fractures and lacerations to visceral organs due to CPR, 
infections and bleedings associated with invasive ventilation and other procedures during 
resuscitation and the post cardiac arrest intensive care period. In this population it is difficult, 
if not impossible, to report all AEs and SAEs and assess their relation to the intervention.  
 
In this trial, two strategies of defibrillation will be compared but all other treatments will follow 
standard care. Therefore, adverse events related to the defibrillation process and intervention 
during resuscitation will be collected with emphasis on device deficiency (DD) and 
anticipated AE (se section 14.3). 
 
The principal investigator or an authorised designee will record: 
• 
- all SADEs;  
• 
- all Device Deficiencies; 
• 
- any new finding in relation to any of the above-mentioned events.  
 
Events that are related to cardiac arrest and would be expected in patients undergoing 
attempted resuscitation should NOT be reported. These include but are not limited to:  
• 
-  Death  
• 
-  Hospitalization  
• 
-  Persistent or significant disability or incapacity  
• 
-  Organ failure 
• 
-  Rib fractures and bleeding related to CPR 
 
In summary, due to the high amount of expected (serious) adverse events caused by the 
condition itself and the treatment of the patients as part of standard care, only study-related 
(S)AEs will be reported immediately. This means all (S)AEs related to participation in this 

 
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study protocol, meaning from double sequential defibrillation, will be reported. All other 
(S)AEs will not be reported. 
 
 
Reporting 
The investigators will report all SADEs and Device Deficiencies to the sponsor, immediately 
but not later than 3 calendar days after investigation site study personnel’s awareness of the 
event. This includes defibrillation malfunction during use or detected errors at defibrillator 
self-test after each use. 
 
 
The sponsor will report to the Swedish Medical Products Agency all of the following 
reportable events:  
• 
any SADE that has a causal relationship with the investigational device, the 
comparator or the investigation procedure, or where such causal relationship is 
reasonably possible; 
• 
any device deficiency that might have led to a SAE if appropriate action had not been 
taken, intervention had not occurred, or circumstances had been less fortunate; and 
• 
any new findings in relation to any event referred to above.  
Reporting by the sponsor will be done by filling out the “Summary Reporting Form” (MDCG 
2020-10/2). The form will be filled in/updated for each reportable event or for new 
findings/updates to already reported events. The form will be transmitted to the Swedish 
Medical Products Agency. For events that indicate an imminent risk of death, serious injury, 
or serious illness and that requires prompt remedial action for other patients/subjects, users 
or other persons or a new finding to it will be reported immediately, but not later than 2 
calendar days after awareness by sponsor of a new reportable event or of new information in 
relation with an already reported event. Any other reportable events or a new finding/update 
to it will be reported immediately, but not later than 7 calendar days following the date of 
awareness by the sponsor of the new reportable event or of new information in relation with 
an already reported event. 
 
 
Assessment of Causality 
The relationship between each adverse event and the investigational device, the comparator 
and the investigation procedure will be assessed and recorded by the investigator and 
sponsor.  
 
The sponsor and investigator will distinguish between SAEs related to the investigational 
device and those related to the procedures, relatedness to both is possible.  
Each SAE will be classified according to four different levels of causality: 
1. Not related  
Relationship to the device, comparator or procedures can be excluded when: 
- the SAE can be attributed to another cause (e.g. an underlying or concurrent illness/ 
clinical condition, an effect of another device, drug, treatment or other risk factors); 
 

 
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- the event has no temporal relationship with the use of the investigational device, or 
the procedures related to application of the investigational device; 
 
- the SAE does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible - and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious adverse 
event; 
 
- the event involves a body-site or an organ that cannot be affected by the device or 
procedure; 
 
In order to establish the non-relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the SAE. 
 
2. Possible 
The relationship with the use of the investigational device or comparator, or the 
relationship with procedures, is weak but cannot be ruled out completely. Alternative 
causes are also possible (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment). Cases where relatedness 
cannot be assessed, or no information has been obtained shall also be classified as 
possible. 
3. Probable 
The relationship with the use of the investigational device or comparator, or the 
relationship with procedures, seems relevant and/or the event cannot be reasonably 
explained by another cause. 
4. Causal relationship 
The SAE is associated with the investigational device, comparator or with procedures 
beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
- the event has a temporal relationship with investigational device use/application or 
procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on; 
- the serious adverse event follows a known response pattern to the medical device 
(if the response pattern is previously known); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use. 
 

 
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In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of the SAE. 
14.3. 
List of foreseeable Adverse events 
 
1. Device deficiency. The inability of one of the defibrillators to deliver energy at defibrillation 
or shut down/reboot. This risk is judged to be exceedingly low based on the preclinical testing 
and the results from the previous trials (likely incidence < 1/100). However, it is impossible to 
rule out. Defibrillation data will be analysed for each case and inability to defibrillate will be 
considered as a SADE. All defibrillator files will be analysed for energy delivery at each 
defibrillation.  
 
2. Any device malfunction that becomes evident at defibrillator self-test or test defibrillations 
performed after each use. There is a theoretical risk that one defibrillator can be damaged by 
the current delivered from the other device during DSD. Please see also 4.2. 
 
3. Perceived adverse event by participating EMS-units will also be collected in CRF1. All 
CRF1 forms with perceived adverse events will be followed up by the sponsor with undue 
delay, the monitor will be informed and the type of adverse event and its relationship with the 
intervention or the investigational device will be judged according to definitions in the CIP.  
 
14.4. 
Monitoring 
 
Monitoring will be performed by a monitor team according to the monitoring plan, please see 
6.8 monitoring plan. 
 
15. 
Premature termination of the clinical investigation  
 
The sponsor may suspend or prematurely terminate either the clinical investigation at an 
individual investigation site or the entire clinical investigation for significant and documented 
reasons. The Swedish Medical Products Agency may suspend or prematurely terminate the 
clinical investigation at the applicable investigation sites. 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation, or 
when so instructed by the Medical Products Agency, the sponsor will suspend the clinical 
investigation while the risk is assessed. The sponsor will terminate the clinical investigation if 
an unacceptable risk is confirmed. The sponsor will inform all investigators.  
The sponsor shall consider terminating or suspending the participation of a particular 
investigation site or investigator in the clinical investigation if monitoring or auditing identifies 
serious or repeated deviations on the part of an investigator. If the suspension or premature 
termination was in the interest of safety, the sponsor shall inform all other principal 
investigators. 

 
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If, in the opinion of the investigator, the clinical observations in the clinical investigation 
suggest that it may be unsafe to continue the investigation at the site, the investigator may 
terminate participation in the investigation after consultation with the sponsor. A written 
statement fully documenting the reasons for such termination will be provided to the sponsor. 
If the clinical investigation is prematurely terminated, the investigators shall promptly inform 
the subjects and take necessary steps to finalise their engagement in the clinical 
investigation. All relevant investigation material must be collected, and accountability 
completed. 
If the clinical investigation is interrupted or terminated prematurely the sponsor will report to 
the Medical Products Agency within 15 days together with a justification. If the sponsor has 
temporarily halted or prematurely terminated the clinical investigation on safety grounds, the 
Medical Products Agency will be informed within 24 hours. A clinical investigation report will 
be prepared within three months of the early termination or temporary halt, irrespective of the 
results. In the event that the clinical investigation is restarted within three months of the 
temporary halt, the sponsor does not have to submit a clinical investigation report until the 
clinical investigation has been completed.  
The final clinical investigation report shall include detail with respect to the temporary halt. 
All patients included before the temporal halt or premature termination will be followed up 
until final planned follow-up after 180 days.  
16. 
Publication policy 
 
The clinical investigation will be registered in a publicly accessible database before the start 
of recruitment activities, and the content will be updated throughout the conduct of the clinical 
investigation and the results entered at completion of the clinical investigation. 
(www.clinicaltrials.org) 
 
The results of the study will be published in international medical journals after study 
completion. Criteria for authorship will follow Vancouver guidelines. The coordinating PI will 
have full access to all data and make the final decision to submit for publication. 
The first and primary manuscript will include the main results including pre-defined primary 
and secondary outcomes up until survival to 30 days.  
Secondary publications include the pre-specified sub studies and an explanatory Bayesian 
analysis.  
16.1 Authorship of the first publication 
Coordinating PI Akil Awad will be first author of the main publication and Gabriel Riva will be 
last author. Additional authorship will be provided to members of the steering committee and 
clinical staff involved in the trial as appropriate.  

 
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A Double-D trial author consortium will be formed, including all other authors. The outline is 
that each participating site may list one author to this consortium, if a site includes over 20 
patients 2 authors, and over 50 patients 3 authors can be added.  
 
 

 
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17. 
Bibliography 
 
1. 
Stryker, Data Sheet LIFEPAK®15 monitor/defibrillato. 2022. 
2. 
Physio-Control, Premarket Approval P160026: Summary of Safety and Effectiveness 
Data (SSED). 2018. 
3. 
Physio-Control, EC Declaration Of Conformity LIFEPAK®15 Monitor/Defibrillator. 
2012. 
4. 
Jerkeman, M., et al., Trends in survival after cardiac arrest: a Swedish nationwide 
study over 30 years. Eur Heart J, 2022. 43(46): p. 4817-4829. 
5. 
Sasson, C., et al., Predictors of Survival From Out-of-Hospital Cardiac Arrest A 
Systematic Review and Meta-Analysis. Circulation-Cardiovascular Quality and 
Outcomes, 2010. 3(1): p. 63-U111. 
6. 
Herlitz, J., Annual report from Swedish cardiac arrest register, in Svenska Hjärt-
lungräddningsregistrets årsrapport 2017, J. Herlitz, Editor. 2017. 
7. 
Soar, J., et al., European Resuscitation Council Guidelines 2021: Adult advanced life 
support. Resuscitation, 2021. 161: p. 115-151. 
8. 
Tateishi, K., et al., Impact of number of defibrillation attempts on neurologically 
favourable survival rate in patients with Out-of-Hospital cardiac arrest. Resuscitation, 
2023. 186: p. 109779. 
9. 
Foster, A.G. and C.D. Deakin, Accuracy of instructional diagrams for automated 
external defibrillator pad positioning. Resuscitation, 2019. 139: p. 282-288. 
10. 
Schmidt, A.S., et al., Anterior-Lateral Versus Anterior-Posterior Electrode Position for 
Cardioverting Atrial Fibrillation. Circulation, 2021. 144(25): p. 1995-2003. 
11. 
Hoch, D.H., et al., Double sequential external shocks for refractory ventricular 
fibrillation. J Am Coll Cardiol, 1994. 23(5): p. 1141-5. 
12. 
Emmerson, A.C., M. Whitbread, and R.T. Fothergill, Double sequential defibrillation 
therapy for out-of-hospital cardiac arrests: The London experience. Resuscitation, 
2017. 117: p. 97-101. 
13. 
Gerstein, N.S., et al., External Defibrillator Damage Associated With Attempted 
Synchronized Dual-Dose Cardioversion. Ann Emerg Med, 2018. 71(1): p. 109-112. 
14. 
Drennan, I.R., D. Seidler, and S. Cheskes, A survey of the incidence of defibrillator 
damage during double sequential external defibrillation for refractory ventricular 
fibrillation. Resusc Plus, 2022. 11: p. 100287. 
15. 
Cheskes, S., et al., Defibrillation Strategies for Refractory Ventricular Fibrillation. N 
Engl J Med, 2022. 387(21): p. 1947-1956. 
16. 
Grasner, J.-T., et al., Cardiac arrest and cardiopulmonary resuscitation outcome 
reports: 2024 update of the Utstein Out-of-Hospital Cardiac Arrest Registry template. 
Resuscitation, 2024. 201: p. 110288. 
17. 
Nolan, J.P., et al., European Resuscitation Council and European Society of Intensive 
Care Medicine Guidelines 2021: Post-resuscitation care. Resuscitation, 2021. 161: p. 
220-269. 
18. 
Soar, J., et al., European Resuscitation Council Guidelines 2025 Adult Advanced Life 
Support. Resuscitation, 2025. 215: p. 110769.