Prediction of Massive Transfusion in Trauma Patients in Prehospital and In-hospital: Data From Swiss Trauma Registry (STR)
Conditions: Trauma Injury, Haemorrhagic Shock, Bleeding, Emergencies, Blood Transfusion, Massive Hemorrhage, Massive Transfusion, Adult, Bleeding Hemorrhage, Hemorrhage / Mortality, Cohort Study, Female, Male, Hospital Mortality, Humans, Models, Theoretical, Prognosis, Wounds and Injuries / Mortality
Sponsor: Centre Hospitalier Universitaire Vaudois

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 1/7 
 
 
PROTOCOL SYNOPSIS 
 
Sponsor / Sponsor-
Investigator 
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland 
Study Title: 
Prediction of massive transfusion in trauma patients in prehospital and 
in-hospital: Data from Swiss Trauma Registry (STR) 
Acronym:  
Massive transfusion Prediction Study (MTP Study) 
Protocol Version and 
Date: 
Version n°1, 11.09.2020 
Trial registration: 
Swiss trauma Registry: NCT0352602 
MTP study: pending 
Study category and 
Rationale 
Our study is an observational non-interventional study based on a 
multicentric swiss register (Swiss trauma Registry) based on 
retrospective anonymized data.  
Clinical Phase: 
No Clinical phase: Observational study 

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 2/7 
Background and 
Rationale: 
Since the 2000s, many prognostic scores were developed to predict 
traumatic haemorrhage. Most of these studies were retrospectives based 
on registers. Due to missing data of death due to bleeding, these studies 
chose to predict the risk of massive transfusion as a surrogate of 
haemorrhagic death. These scores include clinical parameters (Vital 
signs), laboratory values (haemoglobin, lactate, Base excess) and/or 
imaging (CT or ultrasound) values. The scores showing best performance 
are the Trauma Associated Severe Hemorrhage (TASH) score, developed 
and validated on the German register (DGU-Register) (1, 2) and the ABC 
score developed and validated in the United States of America (3, 4). 
However, the majority of these scores cannot be applied at the scene of 
the injury due to the unavailability of laboratory and imaging values. 
Therefore, their clinical utility remains unclear. To overcome the need of 
diagnostic tests, authors have developed and recently validated a clinical 
prognostic score in identifying trauma patients with or at risk of significant 
haemorrhage based on predicted probabilities of death due to bleeding: 
BATT score (5). This score was developed from an international cohort 
using data from 271 Trauma Centres in 41 countries on 5 continents and 
uses first clinical parameters at initial assessment. The BATT score 
predicts death due to bleeding and has been validated on a large 
population in England and Wales. It could also predict massive 
transfusion, as a surrogate of haemorrhagic death, earlier at the scene of 
injury. Its feasibility and external validation would make its clinical utility 
superior to other scores while identifying a greater number of patients 
requiring early management. 
Objective(s): 
- 
External validation of pre-existing prognostic scores of traumatic 
haemorrhages at different times of care (Scene of Injury, 
admission at the trauma room) in order to assess their overall 
performance, discrimination and calibration in the prediction of 
massive transfusion and haemorrhagic death.  
- 
Comparison of score performances (Overall performance, 
discrimination and calibration). 
Outcome(s): 
Primary study outcome :  
- 
Massive transfusion defined by a transfusion equal to or greater 
than 10 Red blood cell (RBC) / 24 hours or ≥ 3 RBC in the first 
hour if available in the Swiss Trauma Registry.  
 
Secondary study outcome :  
- 
Death due to bleeding (if available in the registry) 
- 
Early death (< 24 hours) 
- 
Coagulopathy at admission defined by INR > 1.2, quick TP < 
70% or Fibrinogen < 1.5 g/L (6,7,8)  
Study design: 
Observational non-interventional study based on a multicentric 
anonymized registry 

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 3/7 
Inclusion / Exclusion 
criteria: 
Study population:  
All adult trauma patients treated at twelve Swiss trauma centres Level I 
from 01.01.2015 to 31.12.2019 with eligible criteria of the Swiss Trauma 
Registry (STR) are included. All data from the register are anonymised 
without any access to medical files. The identity of the trauma patients, 
date of birth, address and trauma scene location are unknown (as 
mandatory by the swiss law: Art. 2 ORH). 
Inclusion criteria: 
- 
Age > 16 years old 
- 
ISS (Injury Severity Score) ≥ 16 and/or AIS head (Abbreviated 
Injured scale) ≥ 3 
 
Exclusion criteria:  
- 
Age < 16 years old 
- 
ISS < 16 and or AIS < 3 
- 
Isolated Burns (including electric shock) or if the burn is clearly 
the primary injury 
- 
Patients arriving at the trauma room with no sign of life and no 
diagnostic/therapeutic measures have been initiated for them  
- 
Choking or hanging patient without any other injury. 
- 
Drowning patients 

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 4/7 
Measurements and 
procedures: 
Predictive Variables:  
 
Demographics: Age, gender, type of accident, mechanism of Injury 
(penetrating/blunt), Hospital (anonymised by number), Date and time of 
accident. 
Prehospital settings: Arrival on scene (paramedics, date/time and 
medics, date/time), type of transport: physician staffed 
ambulance/helicopter, Firsts clinical measures recorded: Systolic blood 
pressure (SBP), Respiratory rate (RR), Heart Rate (HR), Pulse Oximetry, 
Glasgow coma scale, temperature, cardiopulmonary reanimation, Drugs 
Use: Tranexamic acid (Date/time) and vasoactive, early death before 
arriving to the hospital. 
 In-hospital settings (trauma room): Hospital arrival (date/hour), Firsts 
measures: Systolic blood pressure (SBP), Respiratory rate (RR), Heart 
Rate (HR), Pulse Oximetry, Glasgow coma scale, temperature, 
cardiopulmonary reanimation, Biological parameters: haemoglobin, 
Platelets, lactates, Base excess, TP (sec and %), INR, PTT, Fibrinogen, 
Drugs use: Tranexamic acid (date/time), vasoactive, Vitamin K, 
Fibrinogen, Prothrombin complex concentrate, rFVIIa, Red blood cell 
(number in the first hour, date/hour of each Red blood cell), platelets 
units, fresh frozen plasma. 
Imaging: type of imaging, results: positive or negative for free fluid, 
date/time of imaging.  
Diagnosis: AIS final, ISS final, Medical past, use of 
anticoagulant/antiaggregant before trauma 
Outcome: Date/time of death, Early death (<12 hours), Early death (<24 
hours), number of red blood cell in 24 hours, Massive transfusion 
(defined as ≥ 10 red blood cells in the first 24 hours). 
 
Depending of the availability of requested variables in the registry, we 
will ask for complementary variables. 
 
Comparison:  
Performance comparison of pre-existing scores (TASH, ABC and BATT 
scores) in term of overall performance, discrimination and calibration.  
 
Evaluation of clinical utility and feasibility in prehospital settings and 
emergency admission. 
Intervention:  
Comparison of score performances (Overall performance, discrimination 
and calibration) 
Control Intervention (if 
applicable): 
No group controls 
Number of 
Participants with 
Rationale: 
The number of participants will depend of the Swiss Trauma Registry 
Database. We project to include 10’000 participants for our study. A 
post-hoc power calculation will be performed. 
Study Duration: 
11 months 
Study Schedule: 
From August 2020 to  June 2021 

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 5/7 
Investigator(s): 
Professor Pierre-Nicolas Carron 
Study Director 
Service des Urgences  
Centre hospitalier Universitaire Vaudois (CHUV)  
Rue du Bugnon 46  
CH-1011 Lausanne  
Email : Pierre-Nicolas.Carron@chuv.ch 
 
Doctor François-Xavier Ageron 
Study Director 
Service des Urgences  
Centre hospitalier Universitaire Vaudois (CHUV)  
Rue du Bugnon 46  
CH-1011 Lausanne  
Email : Francois-Xavier.Ageron@chuv.ch 
 
Alan Costa 
Principal investigator 
Service des Urgences  
Centre hospitalier Universitaire Vaudois (CHUV)  
Rue du Bugnon 46  
CH-1011 Lausanne  
Email : Alan.Costa@chuv.ch 
Study Centre(s): 
Multi-centre study including 12 Swiss Trauma Centre included in the 
Swiss Trauma Registry (Centre Hospitalier Universitaire Vaudois, 
Hôpitaux universitaire Genevois, Inselspital Bern, Universitätsspital 
Basel, Universitätsspital Zürich, Kantonsspital St. Gallen, Luzerner 
Kantonsspital, Kantonsspital Aarau, Kantonsspital Graubünden, 
Kantonsspital Winterthur, EOC – Ospedale Regionale di Lugano, 
Gesundheitsnetwerk Wallis – Standort Sion)  
Statistical 
Considerations: 
Comparison between scores:  
- 
Overall performance: Brier score 
- 
Discrimination: C-statistic, AUROC curve and calculation of 
likelihood ratio, sensitivity and specificity. 
- 
Calibration: Global calibration, calibration curve with intercept 
and slope calibration. 
 
Missing data: To estimate baseline risk for the full dataset, we will 
replace missing predictors using multiple imputation by chained 
equation.  
 
Please referring to the Statistical Analysis Plan 
GCP Statement: 
This study will be conducted in compliance with the protocol, the current 
version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as 
far as applicable) as well as all national legal and regulatory 
requirements. 
 
 
 
 
 

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 6/7 
Study Procedure/Flowchart with Timelines: Study specific Examinations have to be clearly 
identified 
1st step :Request database to the Swiss trauma registry, redacting the statistical analysis plan and 
study registration on Clinicaltrials.org (August-September 2020)  
2nd step: Statistical Analysis (October 2020) 
3rd step: Results (December 2020) 
4th step: Publication 
Storage of Data-and Samples for Future Research Aims: no 
Ethical Considerations: 
1. Please describe the potential gain of new knowledge obtained with this study, and its meaning for 
patients/society.  
 
Answer n°1:  
Due to the study population (Swiss Trauma Registry) which is partly integrated into the German DGU-
Register, we expect good transportability of the TASH score to the Swiss Trauma Registry in term of 
overall performance, discrimination and calibration. The ABC score should show lowers results in terms 
of discrimination due to his validation on small cohorts exclusively in north America. The new BATT 
score predicting death due to bleeding, has been validated on a large English Cohort of more than 
100’000 patients. It identifies all patients with haemorrhage and not only patients who have received a 
massive transfusion subject to survival bias. In this context, the BATT score provides good 
discrimination with only simple physiological variables available on the trauma scene. In case of its 
external validation on the swiss trauma registry as part of our study, its feasibility would make its clinical 
utility superior to other pre-existing scores while identifying a greater number of patients requiring early 
management. Its application would activate a massive transfusion plan directly on the trauma scene and 
save precious time. 
 
 
2. Please give an assessment of the benefit/risk relationship for the patient. 
3. Please explain, why the methodology is also ethically appropriate to gain new generalizable 
knowledge (for ex. double-blind, placebo, sham, vulnerable subjects, emergency cases, partial 
information only etc.) 
 
Answer n°2-3:  
Due to the retrospective aspect of our observational study based on an anonymized register (identity, 
date of birth, trauma scene and hospital location unknown according to the swiss law: Art. 2 HRA), we 
don’t identify any risk of being harmful to our population. In case of external validation of the scores, we 
identify benefits for the population in terms of trauma care. Without any risk for the patient, the potential 
gain of knowledge obtained with this study is high and will contribute to improve trauma care in respect 
of the fundamental principles of Medical ethics. 
 
 
The most relevant References:  
 

s w i s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Protocol Synopsis 
Version 1 of date (11/09/2020) 
page 7/7 
1) 
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2) 
Maegele M, Lefering R, Wafaisade A, et al. Revalidation and update of the TASH-Score: a 
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massive transfusion in trauma: simple as ABC?. J Trauma. 2009;66(2):346‐352.  
4) 
Cotton BA, Dossett LA, Haut ER, et al. Multicenter validation of a simplified score to predict 
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Ageron F-X, Gayet- Ageron A, Steyerberg E, et al. Prognostic model for traumatic death due to 
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Brohi K, Cohen MJ, Davenport RA. Acute coagulopathy of trauma: mechanism, identification 
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