High-Sensitivity Troponin I in Addition to Guideline-Based Care in Emergency Medical Service - an Open Randomized Controlled Trial
Phase: NA
Conditions: Emergency Medical Services, Nursing Care, Cardiology, Myocardial Infarction, Myocardial Infarction or Chest Pain, Myocardial Infarction, Acute, Emergencies, Ambulance
Sponsor: Karolinska Institutet

 
 
TIGER STUDY 
High-Sensitivity Troponin I in Addition to 
Guideline-Based Care in Emergency Medical 
Service - an Open Randomized Controlled Trial 
 
2025-05-15 
 
NCT number: 
 
 

  
 
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TIGER STUDY 
High-Sensitivity Troponin I in Addition to 
Guideline-Based Care in Emergency Medical 
Service - an Open Randomized Controlled Trial 
 
Study Protocol 
 
 
Research question ............................................................................................................................... 4 
Materials and Methods ....................................................................................................................... 4 
Study Design .................................................................................................................................... 4 
Sample Size Calculation ................................................................................................................... 4 
Interim Analysis ................................................................................................................................ 5 
Overall Study Design ....................................................................................................................... 5 
Procedures and Flowchart............................................................................................................... 5 
Data Collection ................................................................................................................................ 6 
Screening ......................................................................................................................................... 6 
Inclusion Criteria.................................................................................................................................. 6 
Exclusion Criteria ................................................................................................................................. 6 
Randomization ................................................................................................................................ 6 
Blinding ............................................................................................................................................ 7 
Statistical Analyses .............................................................................................................................. 7 
Potential Confounders .................................................................................................................... 7 
Outcome Measures ............................................................................................................................. 7 
Primary Outcome Measure ............................................................................................................. 7 
Secondary Outcome Measures ....................................................................................................... 7 
Risk-Benefit Assessment ..................................................................................................................... 8 
Biological Sampling Procedures .......................................................................................................... 9 

  
 
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Handling, Storage, and Destruction of Biological Samples ............................................................. 9 
Total Blood Volume per Participant ................................................................................................ 9 
Biobank ............................................................................................................................................ 9 
Trial Termination ............................................................................................................................. 9 
Withdrawal Criteria and Incident Management ............................................................................... 10 
Authorship ......................................................................................................................................... 10 
 
 
 
 

  
 
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Introduction 
In Sweden, a myocardial infarction (MI) occurs approximately every twenty minutes, 
affecting individuals across all ages and genders. Early detection of these cases is critical to 
enable the prompt initiation of life-saving interventions. Within the emergency medical 
service (EMS) of Region Stockholm—handling over 200,000 patient cases annually—chest 
pain accounts for between 10% and 12% of all assignments. However, currently only a 
limited proportion of patients with MI can be diagnosed prehospitally using ECG, requiring 
the majority of patients to undergo further evaluation through high-sensitivity troponin 
blood testing at emergency departments. Streamlining this diagnostic process within the 
prehospital emergency care setting has the potential to optimize patient flow, reduce 
unnecessary healthcare costs, and—most importantly—significantly shorten patient 
suffering. 
 
The objective of the study is to evaluate the clinical utility of a point-of-care high-sensitivity 
Troponin I analysis in prehospital emergency care, in patients presenting with chest pain or 
in whom ambulance personnel suspect a MI. By facilitating earlier diagnosis of myocardial 
infarction, the project seeks to improve patient outcomes through more rapid identification 
and treatment of this time-critical condition. 
 
Sponsor: Region Stockholm, through Ambulance Services in Greater Stockholm (AISAB) 
Principal Investigator: Jakob Lederman, jakob.lederman@ki.se 
Responsible for Current Study Information: Sebastian Bjöhle, sebastian.bjohle@ki.se 
Original Protocol Version Date: 2024-03-21 
Most Recent Protocol Amendment Date: 2025-05-15 
Condition Studied: Myocardial Infarction 
Research question 
What is the added value of using high-sensitivity Troponin I in prehospital emergency care—
beyond current guideline-based care —for the early identification of patients with 
myocardial infarction? 
Materials and Methods 
Study Design 
This is an open, randomized controlled trial with a 2:1 allocation ratio. After obtaining 
informed consent from the patient, the ambulance personnel will perform digital 
randomization to either the intervention or control group. 
Sample Size Calculation 
To ensure sufficient statistical power, a power calculation was conducted. It is based on the 
assumption that the use of high-sensitivity Troponin I in prehospital emergency care will 
result in a 50% improvement in the identification of patients with MI, with a 2:1 ratio 
between the intervention and control groups. With a significance level (alpha) of 0.05 and a 
power of 80%, the total number of required participants was calculated. To account for 
potential dropouts—such as unsuccessful sampling or incomplete data—an additional 10% 
was added. This resulted in a total required sample size of 1,419 participants, distributed as 
946 in the intervention group and 473 in the control group. 

  
 
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Interim Analysis 
An interim analysis will be conducted by external researchers after the inclusion of the first 
150 participants. The purpose is to ensure the validity and reliability of the study, confirm 
adherence to the protocol, and identify any unforeseen risks. The principal investigator will 
make the final decision regarding any potential discontinuation of the study. 
Overall Study Design 
This is an open, randomized controlled trial with parallel group allocation (intervention or 
control) using an intention-to-treat (ITT) approach. In the intervention group, blood sampling 
will be performed during the prehospital care period by ambulance personnel. The result is 
communicated via the EMS medical record system (FRAPP), along with the transmitted ECG 
and during verbal handover to the receiving hospital. Final clinical decisions are made by the 
receiving physician based on the overall clinical assessment. Follow-up will only be 
conducted by the research team via electronic health record review and data extraction 
from the Swedeheart register, no direct follow-up with participants will take place. 
Procedures and Flowchart 
All EMS personnel participating in the study will undergo training on the use of the point-of-
care testing device and receive study-specific information prior to study initiation. In 
addition, they will be informed by the Principal Investigator about legal requirements and 
procedures for obtaining informed consent. Only EMS personnel who have completed this 
training will be authorized to recruit and collect samples from participants. 
 
When a patient is assessed as eligible for inclusion, informed consent will be obtained. The 
responsible prehospital emergency nurse (or other nurse with specialist training) at each 
study site must ensure that the participant receives comprehensive oral and written 
information about the study, its purpose, potential risks and benefits, and 
inclusion/exclusion criteria. Participants must be informed of their right to withdraw at any 
time without providing a reason. Adequate time must be given for questions and 
consideration. If a patient is deemed unable to understand the provided information, they 
will be excluded from participation. 
 
If the patient agrees to participate, the consent form is signed electronically, and a copy is 
provided to the participant. The signed and dated consent must be obtained and 
documented in the Case Report Form (CRF) before any study-specific procedures are carried 
out. Each participant will be assigned a unique study ID, and consent will include permission 
for the research team to access their medical records and source data. If new relevant 
information arises during the study, participants will have the opportunity to reassess their 
continued participation. 
 
Following consent, a CRF will be initiated, and randomization to the intervention or control 
group will take place electronically within the CRF system. 
Control Group: Will receive guideline-based care (i.e. standard of care) according to current 
medical guidelines. 

  
 
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Intervention Group: Will receive guideline-based care (i.e. standard of care) according to 
current medical guidelines plus a point-of-care high-sensitivity Troponin I test. 
 
The Troponin I test will be performed on 0.03–0.1 mL of capillary or venous blood, 
preferably collected in parallel with EKG registration or IV access to avoid delays in care. The 
test is open-label, and results will be visible to EMS personnel and the patient within 
approximately 8 minutes. 
 
The Troponin I level is communicated via the EMS medical record system (FRAPP), along with 
the transmitted ECG and during verbal handover to the receiving hospital. Final clinical 
decisions are made by the receiving physician based on the overall clinical assessment. 
Follow-up will only be conducted through the participant’s electronic health records and 
data extraction by the research team. No additional contact will be made with the 
participant. 
 
Point-of-care testing device: 
Siemens Atellica VTLi 
Data Collection  
Following informed consent, data will be collected using an electronic Case Report Form 
(eCRF) via REDCap, completed by EMS personnel. Additional data sources include the 
patient’s electronic medical record, the EMS medical record system (FRAPP), Region 
Stockholm healthcare administrative data warehouse (VAL), and the national quality registry 
Swedeheart via UCR (Uppsala Clinical Research Center). 
Screening 
Before randomization, it must be confirmed that the participant meets all inclusion criteria 
and does not meet any exclusion criteria. The inclusion decision should be made in parallel 
with ongoing patient care to avoid delaying transport to the hospital. 
 
Inclusion Criteria 
o Adult patients (≥18 years) 
o Presenting with chest pain or with a clinical suspicion of myocardial infarction as 
assessed by EMS personnel 
Exclusion Criteria 
o No valid Swedish personal identity number 
o Lacks the capacity to provide informed consent 
o Not a primary EMS assignment 
o Trauma Level 1 case 
Randomization 
Electronic randomization with a 2:1 allocation ratio will be performed during the prehospital 
care phase by EMS personnel using REDCap, after informed consent has been obtained. 
Participants will be randomized into one of the following study arms: 
 

  
 
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 Study Arm 1: Intervention Group 
Participants will receive guideline-based care (i.e. standard of care) according to 
current medical guidelines plus a point-of-care high-sensitivity Troponin I test. 
 Study Arm 2: Control Group 
Will receive guideline-based care (i.e. standard of care) according to current medical 
guidelines. 
Blinding 
The study will be conducted using an open-label design. 
Statistical Analyses 
See separate statistical analysis plan for the TIGER study. 
Potential Confounders 
Potential confounding factors include conditions that may elevate troponin levels in the 
absence of MI, such as pulmonary embolism, sepsis, renal failure, atrial fibrillation, and heart 
failure. Additional potential confounders include sex, frailty, age, and time from symptom 
onset. 
Outcome Measures 
Primary Outcome Measure 
1. Time from First Medical Contact (FMC) to PCI (minutes) 
Defined as the time from ambulance arrival to percutaneous coronary 
intervention (PCI). 
 
Secondary Outcome Measures 
1. Length of Stay (hours) 
Total duration of care (prehospital and in-hospital) per study arm. Subgroup 
analyses will be conducted based on potential confounders. 
 
2. MACE (Major Adverse Cardiac Events) within 72 hours and 30 days 
Occurrence of MACE in each study arm. Subgroup analyses will be performed 
based on potential confounders. 
MACE is defined as: 
a) MI 
b) Angina Pectoris 
c) New-onset heart failure (HFrEF) 
d) Stroke 
e) All-cause death 
 
3. Intervention 
Description: Number and type of interventions 
Time Frame: FMC-to-hospital discharge 
 
4. Level of care 

  
 
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Distribution of admission location in each study arm, with subgroup analyses by 
potential confounders: 
a) Emergency Department (ED) 
b) Coronary Care Unit (CCU) 
c) Direct PCI 
d) Other intermediate care unit 
e) Other cardiac unit 
f) Other general ward 
g) Other healthcare facility 
 
5. Clinical Utility of Point-of-Care Troponin I Testing in EMS 
Assessment of the diagnostic performance of Troponin I for early identification 
of MI in the prehospital setting (Sensitivity, Specificity, Negative Predictive 
Value (NPV) and Positive Predictive Value (PPV)) 
Subgroup analyses will be conducted based on potential 
confounders: 
Overall 
By time from symptom onset (≤120 min, 121–179 min, ≥180 min) 
6. Incidence of Time-Critical Diagnoses Other Than MI (within 30 days) 
Number of patients in the intervention group (Study Arm 1) with negative vs 
positive troponin results who receive a discharge diagnosis of another time-
critical condition (excluding MI). Subgroup analyses will be performed based on 
potential confounders. 
 
Risk-Benefit Assessment 
In today’s healthcare system, emergency departments face increasing pressure from 
overcrowding, while the number of EMS dispatches for chest pain continues to rise. Despite 
this, only a small proportion of these cases result in a confirmed diagnosis of MI, a time-
critical condition. According to the latest treatment guidelines from the European Society of 
Cardiology (ESC), a growing share of patients requires urgent coronary intervention. There is 
potential benefit in enabling EMS personnel to identify MI at an earlier stage, which may 
facilitate faster monitoring and treatment and thereby reduce the risk of complications and 
mortality. 
 
This study aims to explore the clinical value of introducing early point-of-care testing for 
Troponin I to improve prehospital detection of MI. Patients are included based on EMS 
personnel's clinical judgment and the provision of informed consent. Only EMS personnel 
who have received specialized training will be authorized to enroll participants. This training, 
provided in collaboration with the principal investigator, covers procedures for obtaining 
informed consent, cardiac care principles, Troponin testing, and the use of relevant 
equipment. 
 
The study does not alter standard clinical management, aside from an additional blood 
sample analyzed using a point-of-care device. Troponin testing is already standard procedure 
at hospitals and results are interpreted in accordance with medical directives. If an elevated 

  
 
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troponin level is detected prehospitally, the cardiologist on call is informed either by phone 
or via the digital communication platform used by EMS. Blood sampling may cause minor 
discomfort, which is minimized by coordinating sampling with the establishment of 
peripheral IV access or other routine procedures. 
 
Participants receive both oral and written information about the study and are informed of 
their right to withdraw at any time. The study's impact on length of hospital stay will be 
monitored through interim analyses conducted by an independent researcher. Should a 
significant increase in treatment time be observed, the principal investigator will consider 
discontinuing the study or modifying its procedures. 
 
The risks to participating patients are considered low. Potential benefits include earlier 
detection of MI and thus more rapid access to treatment. This interventional study aims to 
enhance early decision-making by introducing high-sensitivity troponin testing into 
prehospital care. The implementation of point-of-care diagnostics is viewed as a strategic 
reinforcement of EMS capabilities. 
 
The informed consent process is critical and includes thorough patient education, assurance 
of the right to withdraw without consequence, and confirmation that standard care will not 
be negatively affected. Privacy risks are minimized through pseudonymization and restricted 
data access. 
 
In conclusion, a comprehensive evaluation indicates that the risks to participants are low, 
while the potential for improved early detection and timely treatment of MI—ultimately 
reducing morbidity and mortality—represents a substantial benefit. From an ethical 
perspective, the consent process is robust and safeguards patient autonomy, resulting in an 
overall favorable risk-benefit profile. 
 
Biological Sampling Procedures 
Handling, Storage, and Destruction of Biological Samples 
No biological material will be stored after the analysis has been completed during the 
relevant episode of care in prehospital emergency services. The blood sample will be 
destroyed by the responsible EMS personnel after the care encounter, in accordance with 
standard operating procedures in EMS. 
Total Blood Volume per Participant 
The total blood volume collected from each participant during the trial will not exceed 0.1 
mL. 
Biobank 
No samples collected during the trial will be stored. No biobank will be established. All 
samples will be destroyed after the care episode, following EMS standard procedures. 
Trial Termination 

  
 
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The trial will conclude once follow-up of the final participant has been completed. The study 
may be terminated early if necessary for safety reasons that impact the risk-benefit 
assessment or if participant recruitment cannot be achieved within a reasonable timeframe. 
Decisions regarding early termination or modification of the study process will be made by 
the Principal Investigator. 
Withdrawal Criteria and Incident Management 
Participants may withdraw from the trial at any time without any consequences for their 
ongoing medical care or treatment. If a participant withdraws consent during the course of 
the study, data collected up to that point will be retained and used for analysis and 
reporting. However, any further data collection will cease upon receipt of the withdrawal, 
and no additional information will be gathered from the participant. This approach ensures 
respect for individual autonomy while allowing for the ethical and responsible use of 
previously collected research data. 
 
Incidents will be reported and followed up according to the standard deviation reporting 
procedures in EMS. The outcomes of interim analyses will be reviewed by the research team. 
The Principal Investigator holds responsibility for deciding whether the study should be 
discontinued. 
 
Authorship 
Sebastian Bjöhle, Veronica Vicente, and Jakob Lederman