Reperfusion Treatment in Acute Pulmonary Embolism: A Multicenter Observational Study in the Nordic Countries
Conditions: Pulmonary Embolism
Sponsor: Sahlgrenska University Hospital

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
Date: 250520 / Version: 1.2 
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Reperfusion Treatment in Acute Pulmonary Embolism: A Multicenter Observational Study in 
the Nordic Countries (PE-NORDIC) 
 
Sponsor: Region Västra Götaland, Regionens Hus, 462 80 Vänersborg, Sweden 
 
Principal Investigator: Kristina Svennerholm, Sahlgrenska University Hospital, Gothenburg, Sweden 
 
Study coordinators:  
Kristina Svennerholm, kristina.svennerholm@vgregion.se, +46 708 117 993 
Freyr Einarsson, freyr.einarsson@vgregion.se, +46 705 769 662 
 
Steering committee: Kristina Svennerholm, Freyr Einarsson, Christian Rylander, Katarina Glise Sandblad, 
Mazdak Tavoly, Asger Andersen, Aldina Pivodic  
 
Statistician: Aldina Pivodic, aldina.pivodic@apnc.se 
 
Clinical research coordinator: Annika Odenstedt, annika.odenstedt@vgregion.se  
 
Clinical Studies Sweden:  
Gothia Forum  
Sahlgrenska University Hospital 
413 45 Gothenburg, Sweden 
Tel: +46 31 3429679 
 
Benny Jönsson (eCRF, DMP), benny.jonsson@vgregion.se 
 
Sites and investigators 
 
Sweden 
 
Sahlgrenska University Hospital, Gothenburg: Kristina Svennerholm, Freyr Einarsson, Mårten Falkenberg, 
Louise Martinell, Sebastian Völz (CDI), Mazdak Tavoly (ST SU/S), Katarina Glise Sandblad (ST SU/Ö), Maria 
Roupe (ST SU/M), Jenny Danielsbacka, Annika Odenstedt (research nurse)  
 
Uppsala University Hospital, Uppsala: Christian Rylander, Erik Bruno (ST) 
 
Södersjukhuset, Stockholm: Jacob Hollenberg (CDI), Mårten Söderberg (ST) 
 
Danderyd Hospital, Stockholm: Fadi Jokhaji (CDI), Eli Westerlund (ST), Mika Skeppholm (ST) 
 
Karolinska University Hospital Solna, Sthlm: Jan Engström (CDI), Therese Djärv (ST) 
 
Karolinska University Hospital Huddinge, Sthlm: Yngve Forslin (CDI), Therese Djärv (ST) 
 
Linköping University Hospital, Linköping: Petr Vorel (CDI), Margareta Holmström (ST) 
 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
Date: 250520 / Version: 1.2 
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Sunderby Hospital, Luleå: Nils Witt (CDI), Tobias Hegner (ST) 
 
Örebro University Hospital: Fredrik Calais (CDI), Robin Gustafsson (ST) 
 
 
Malmö/Lund University Hospital: Josef Dankiewicz (CDI), Johan Elf (ST) 
 
Denmark 
Aarhus University Hospital: Asger Andersen, Elisa Stilling 
 
Odense University Hospital: Gro Egholm 
 
Rigshospitalet: Jesper Kjærgård 
 
 
 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
Date: 250520 / Version: 1.2 
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Synopsis  
Title: 
Reperfusion Treatment in Acute Pulmonary Embolism: A Multicenter Observa-
tional Study in the Nordic Countries (PE-NORDIC) 
Ethics: 
Approved by the Swedish Ethical Review Authority Dnr 2019-00827, amendments: 
Dnr 2022-04256-02 Dnr 2023-04750-02 Dnr 2023-06931-02 Dnr 2024-00038-02 Dnr 
2024-04908-02 2025-00546-02  
 
Background: 
International guidelines recommend immediate reperfusion with systemic thrombo-
lysis (ST) as first-line treatment in high-risk pulmonary embolism (PE) [1]. The therapy 
improves haemodynamics and overall survival but is also associated with a significant 
risk of severe bleeding [2]. Catheter directed intervention (CDI) is recommended as 
an alternative reperfusion therapy in high-risk PE when ST is contraindicated or has 
failed, as well as in patients who deteriorate or fail to improve during anticoagulation 
(AC) treatment [1]. Despite lack of high-quality evidence and randomized studies be-
tween CDI and standard care, the use of CDI is spreading rapidly in high-risk PE and 
in less severe PE not fulfilling current treatment criteria [3].  
 
Several CDI methods are available, including mechanical thrombectomy (MT) and 
catheter-directed thrombolysis (CDT), but no method is currently recommended over 
the other. In Sweden, the MT device FlowTriever® (FT) was introduced in 2021 and 
has since then been the predominant method. Industry sponsored trials have inves-
tigated FT in uncontrolled observational trials and primarily in intermediate-risk PE 
[3-4]. In the prospective non-randomized trial FLAME, high-risk PE treated with FT 
was associated with a lower mortality and incidence of bleeding compared to a con-
text arm [5]. The recently published PEERLESS trial was the first randomized con-
trolled trial (RCT) to compare different CDI methods, with patients with intermediate-
risk PE being randomized to either MT with FT or CDT [6]. The investigator-initiated 
research on FT is limited to relatively small, descriptive, single-arm studies, or trials 
focusing on intermediate-risk PE [7-9].  
 
There are several ongoing trials comparing different CDI methods to anticoagulation. 
However, in clinical practice, patients with acute PE may be subjected to different 
reperfusion strategies depending on severity and available resources. The PE-NOR-
DIC observational study will compare the outcomes of different patient groups 
treated with current CDI methods used in the Nordic countries to patients treated 
with ST. 
Objective: 
To evaluate short- and long-term outcomes among patients treated with CDI and to 
compare it to patients treated with ST for acute PE. 
Design: 
Prospective multicenter observational cohort study. 
Countries: 
Sweden, Denmark 
Timetable: 
A three-year inclusion period, Q2 2025 – Q2 2028. 
2028: Data analysis, concluding patient follow-up, publishing results. 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
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Population: 
Adult patients with acute PE treated with CDI or ST 
Eligibility: 
Inclusion criteria:  
• All adult patients (≥18 years), including pregnant women, with verified 
(CTPA, angiography or scintigraphy) acute PE who are planned for, or have 
received, treatment with CDI or ST 
• Informed consent (for patients who do not survive before informed con-
sent can be obtained, a waiver of consent applies)  
 
Exclusion criteria: 
• Ongoing enrolment in interventional CDI trial 
• Surgical embolectomy as primary reperfusion treatment 
Primary out-
come: 
The primary outcome is a composite of death from any cause or severe bleeding ac-
cording to GUSTO (defined as intracranial bleeding or bleeding with substantial he-
modynamic compromise requiring treatment) at day 30 after treatment.  
Secondary 
outcomes: 
Within 30 days: All-cause mortality, cause of death, bleeding (according to GUSTO 
criteria), need for rescue treatment (including ST, CDI, extracorporeal membrane ox-
ygenation (ECMO), surgical embolectomy), recurrent PE, hospital and intensive care 
unit (ICU) and/or high dependency unit (HDU) free days and change in right ventric-
ular to left ventricular (RV/LV) ratio before and within 72 h after treatment. 
 
Within 1 year: Persisting dyspnea, RV dysfunction, ECG, cardiac biomarkers, 6-minute 
walk test (6MWT) and health-related quality of life assessments. Potential cases of 
confirmed chronic thromboembolic pulmonary vascular disease (CTED) or chronic 
thromboembolic pulmonary hypertension (CTEPH) during the study period will be 
registered. 
 
 
 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
Date: 250520 / Version: 1.2 
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Title: Reperfusion Treatment in Acute Pulmonary Embolism: A Multicenter Observational Study 
in the Nordic Countries (PE-NORDIC) 
 
Timeline 
 
• Q2 2025 – Q2 2028: Participant inclusion, informed consent, prospective data collection 
• 2025: Register the trial at ClinicalTrials.gov. 
• 2025: Write and submit study protocol for peer-review in scientific journal 
• 2028: Processing and analyzing data, summarizing and interpreting results, writing man-
uscript and submitting for peer-review in a scientific journal. 
 
Background 
 
Current international guidelines recommend systemic intravenous thrombolysis (ST) for high-risk 
pulmonary embolism (PE). ST is an effective dissolvent of thromboembolic clots and has been 
shown to decrease the combined outcome of mortality and recurrent PE [1]. However, ST carries 
a substantial bleeding risk including fatal or intracranial hemorrhage [2]. The risk of bleeding is 
compounded by the fact that many risk factors for PE, such as recent surgery or cancer, also serve 
as contraindications for ST. According to guidelines catheter-directed interventions (CDI) is rec-
ommended in high-risk PE when ST is contraindicated or has failed. CDI is also recommended as 
an alternative in PE patients undergoing anticoagulation therapy in case of treatment failure, 
such as lack of improvement or haemodynamic deterioration [1]. 
 
Several methods of CDI are available, but no method is recommended over the other. In Sweden, 
the mechanical thrombectomy (MT) device FlowTriever® (FT) was introduced in 2021 and has 
since then been the predominant method. It combines large-bore aspiration with expanding 
mesh disks designed to trap and subsequently retract blood clots.  
 
Studies evaluating FT are mainly company-initiated, single-arm trials assessing short-term out-
comes. Furthermore, these studies primarily include patients with less severe PE who do not 
meet guideline criteria for CDI treatment [3-6]. PEERLESS, the first RCT to compare different CDI 
methods in PE, intermediate-risk PE patients were randomized to either FT or catheter-directed 
thrombolysis (CDT), however without including standard care as a comparator [6]. In FLAME, an 
observational study, high-risk PE treated with FT was associated with a lower mortality and inci-
dence of bleeding compared to a context arm [5]. Investigator-initiated trials on MT mainly con-
sist of single-arm studies with focus on intermediate-risk PE, with some small case-series on high-
risk patients [7-9]. 
 
Treatment of acute PE using CDI is an evolving strategy as to techniques and availability. Follow-
up of outcomes and safety is important when new techniques are employed. The PE-NORDIC 
(Reperfusion Treatment in Acute Pulmonary Embolism: A Multicenter Observational Study in the 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
Date: 250520 / Version: 1.2 
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Nordic Countries) study will evaluate short- and long-term safety and effect outcomes in patients 
with PE treated with CDI and ST in Sweden and other Nordic countries.  
 
Aim and hypothesis 
 
The aim is to evaluate short- and long-term outcomes of patients with acute PE treated with CDI 
and compare short- and long-term outcome to a group of patients treated with ST. 
 
We hypothesize that patients with acute PE treated with CDI, as compared to patients treated 
with ST, will have a lower composite incidence of severe bleeding and death, within 30 days. 
 
Study design 
 
This is a prospective observational multicenter study in Sweden with short- and long-term follow-
up. The Nordic countries (Denmark, Norway, Finland and Iceland) are currently engaged in dis-
cussions about potential participation. All centers offering CDI for PE in the study countries will 
be invited to participate. Data will include patient characteristics, clinical examinations, physio-
logical parameters, diagnostics, interventional procedures, laboratory analyses, as well as physi-
cal and psychological functional assessments.  
 
All PE patients become eligible once they have been assigned to either CDI or ST (independent of 
dose) by a documented decision from the treating physician. Patients will be asked for consent 
when assessed capable of understanding the information and making an informed decision. Pro-
spective data collection will begin as soon as consent is obtained. For patients in Sweden who do 
not survive before informed consent can be obtained, a waiver of consent applies, and their data 
will be collected retrospectively. 
 
The data set includes variables from the following stages of the individual patient trajectories 
(Table 1): 
 
• Before treatment (within 24 hours) 
• After treatment (within 72 hours) 
• 30 days after treatment 
• Follow-up visit 1 (within 3-6 months)  
• Follow-up visit 2 (within 9-12 months)  
Follow-up 
During each follow-up visit persisting dyspnea, right ventricular dysfunction, cardiac biomarkers, 
mortality, functional outcomes, as well as questionnaires regarding health-related quality of life. 
Potential cases of confirmed chronic thromboembolic pulmonary vascular disease (CTED) or 
chronic thromboembolic pulmonary hypertension (CTEPH) during the study period will be regis-
tered. 
 
Table 1. Study activities  

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
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Activities 
Before treat-
ment 
After treatment 
(within 72 hours) 
Follow-up visit 1 
Follow-up visit 21 
Informed consent 
x 
x 
x 
x 
Echocardiogram 
x 
x 
  x2 
  x2 
ECG 
x 
x 
x 
x 
Lab tests 
  x3 
  x3 
 x4 
  x4 
Vital parameters 
x 
x 
 
 
Patient surveys 5 
 
 
x 
x 
6MWT & STS606 
 
 
x 
x 
1 A second follow-up visit will not be performed if findings from follow-up visit 1 are normal to 
the extent that no further follow-up is required according to standard clinical practice  
2 No echocardiogram will be performed if findings from previous echocardiogram are normal to 
the extent that it is not required according to standard clinical practice  
3 Troponin, NT-proBNP, creatinine, pH, lactate, PaO2, PaCO2 
4 Troponin, NT-proBNP, creatinine 
5 MRC, EQ-5D, PeMB-QoL, PVFS 
6 6-minute walk test and sit-to-stand 60 test 
 
Patient population 
Inclusion criteria: 
• All adult patients (≥18 years), including pregnant women, with verified (CTPA, angi-
ography or scintigraphy) acute PE who are planned for, or have received, treatment 
with CDI or ST 
 
• Informed consent (for patients who do not survive before informed consent can be ob-
tained, a waiver of consent applies, and their data will be collected retrospectively) 
 
Exclusion criteria: 
• Ongoing enrolment in interventional CDI trial 
• Surgical embolectomy as primary reperfusion treatment 
 
Included patients will be divided into two groups for comparison 
Intervention group: Patients treated with CDI. 
Comparison group: Patients treated with ST.  
Patients treated with ST before CDI will be described separately and excluded from all compara-
tive analyses.  
Primary outcome 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
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The primary outcome is a composite of death from any cause or severe bleeding according to 
GUSTO (defined as intracranial bleeding or bleeding with substantial hemodynamic compro-
mise requiring treatment) at day 30 after treatment.  
 
Secondary outcomes  
Within 30 days: All-cause mortality, cause of death, bleeding (according to GUSTO criteria, se-
vere/non-severe), need for rescue treatment (including ST, CDI, extracorporeal membrane oxy-
genation (ECMO), surgical embolectomy), recurrent PE, hospital and intensive care unit (ICU) 
and/or high dependency unit (HDU) free days and change in right ventricular to left ventricular 
(RV/LV) diameter ratio before and within 72 h after treatment. 
Within 1 year: Persisting dyspnea, RV dysfunction, ECG, cardiac biomarkers, 6-minute walk test 
(6MWT) and sit-to-stand 60 test, health-related quality of life assessments. Potential cases of 
confirmed chronic thromboembolic pulmonary vascular disease (CTED) or chronic thromboem-
bolic pulmonary hypertension (CTEPH) during the study period will be registered. 
 
Study variables 
Baseline characteristics  
• Date of birth 
• Gender  
• Height 
• Weight 
• Ongoing pregnancy/post-partum period 
• Comorbidities  
o Hypertension 
o Ischemic heart disease  
o Chronic heart failure 
o Diabetes  
o COPD 
o Previous stroke  
o Chronic renal failure 
o Active cancer 
o Previous venous thromboembolism  
• Clinical frailty scale* 
• Referral from other hospital 
• Cardiac arrest (0-24 hours before treatment) and ROSC 
• Syncope (0-48 hours before treatment) 
• Invasive mechanical ventilation (0-24 hours before treatment) 
• The highest amount of oxygen administered to achieve target saturation* (0-24 hours 
before treatment) 
• Maximum heart rate (0-24 hours before treatment) 

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• Minimum systolic blood pressure (SBP) (0-24 hours before treatment) 
• Shock index at the minimum SBP (0-24 hours before treatment) 
• Maximum respiratory frequency (0-24 hours before treatment) 
• ECG (0-24 hours before treatment) 
• Maximum lactate level (0-24 hours before treatment) 
• Lowest pH level (0-24 hours before treatment) 
• Maximum cardiac troponin level (0-24 hours before treatment) 
• Maximum NT-proBNP level (0-24 hours before treatment) 
• Maximum creatinine level (0-24 hours before treatment) 
• Estimated glomerular filtration rate (eGRF) at time of maximum creatinine measure-
ment 
• Lowest arterial pO2 (0-24 hours before treatment) 
• Highest arterial or venous pCO2 (0-24 hours before treatment) 
• Treatment with ECMO  
• Diagnostic method of PE (CTPA/Angiography/Scintigraphy) 
• Distribution of pulmonary embolism (i.e. unilateral or bilateral) 
• Most proximally engaged lung segment (central or segmental or subsegmental) 
• Right ventricular/left ventricular ratio (RV/LV ratio) on CT 
• Echocardiogram (0-48 hours before treatment) 
o Left ventricular ejection fraction (LVEF, %) 
o Right ventricular diameter (maximum, mm) 
o Left ventricular diameter (maximum, mm) 
o Tricuspid annular plane systolic excursion (TAPSE, mm) 
o Tricuspid regurgitation grade (0-5) 
o Maximum/minimum inferior vena cava (IVC) diameter (mm) 
o Maximum tricuspid regurgitation velocity (TRV-max) (m/s) 
o Intracardiac thrombus (yes/no) 
o McConnell sign (yes/no) 
o Pulmonary artery acceleration time (ms) 
o RVOT VTI (cm) 
o RVOT mid systolic notch (yes/no) 
o RV fractional area change (%) 
o RV lateral annular systolic velocity (cm/s) 
o D-sign (yes/no) 
o LVOT VTI (cm) 
o LVOT area (cm2) 
o LV inner diameter in diastole (PLAX, mm) 
 
Details of reperfusion treatment variables 
• Time from diagnostic radiology to start of treatment 

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• Indication for reperfusion treatment including: 
o Circulatory instability 
§ Cardiac arrest 
§ SBP < 90 mmHg 
§ Drop in SBP of 40 mmHg for at least 15 minutes 
§ Need for vasopressors to achieve a SBP >90 mmHg (despite an 
adequate filling status, in combination with end-organ hypoperfusion) 
o Lack of improvement from anticoagulant treatment 
o Deterioration during anticoagulant treatment 
o Other 
§ Respiratory failure 
§ Syncope 
§ Severe right heart strain 
§ Thrombus burden 
§ Significant clinical concern 
 
Details of treatment with CDI 
• Indication for intervention including: 
o Absolute or relative contraindication to systemic thrombolysis 
o Insufficient treatment effect of systemic thrombolysis 
o Other 
§ Clinical concern for bleeding without contraindication to systemic throm-
bolysis 
§ Location of thrombosis and/or extent of thrombosis 
• Methods/catheters used 
• Dose and agent for patients treated with catheter-directed thrombolysis 
• Procedure duration 
• Use of autologous blood transfusion 
• Volume of blood transfusion 
• SPAP before and after treatment 
• Successful catheterization 
• Successful thrombus extraction/treatment  
• Clinical improvement after completed intervention 
• Procedural complications 
 
Details of treatment with ST 
• Dose, agent and duration of thrombolysis 
• Premature discontinuation of thrombolysis (yes/no, cause) 
 
Outcome-related variables within 72 hours after treatment  
 

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• Cardiac arrhythmia requiring treatment  
o Type of arrhythmia 
o Treatment received 
 
• Echocardiogram** 
• At the time of echocardiogram (variables closest in time):  
o Mechanical ventilation  
o Need for vasopressors/inotropes 
o FiO2 
o Lab tests: Troponin, NT-proBNP, creatinine, eGRF, pH, lactate, PaO2, 
PaCO2/PvCO2 
o Vital parameters: heart rate, respiratory rate, blood pressure 
o ECG 
 
Outcome-related variables day 30 
• All-cause mortality 
• Cause of death  
• Incidence of severe bleeding (GUSTO criteria) 
• Incidence of any bleeding  
• Site of bleeding 
• Rescue treatment including ST, CDI, surgical embolectomy and ECMO 
• Recurrent PE 
• ICU/HDU length of stay (LOS) 
• Hospital LOS 
 
Outcome-related variables at first follow-up, 3-6 months after treatment 
• All-cause mortality and date of death 
• Marital status 
• Occupation 
• Highest level of education 
• Lab tests: Troponin, NT-proBNP, creatinine, estimated glomerular filtration rate (eGFR)  
• Echocardiogram** (not performed in cases where findings from previous echocardiogram 
are normal to the extent that it is not required according to standard clinical practice)  
• ECG 
• Dyspnea at first follow-up in comparison to discharge 
• Functional outcome (6-minute walking test and sit-to-stand 60 test) 
• MRC (0-4) 
• Generic health-related quality of life assessment (EQ-5D-5L)  
• Disease-specific health-related quality of life (PeMB-QoL) 
• Post venous thromboembolism functional status scale (PVFS)  

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• 6-minute walk test  
• Sit-to-stand 60 test 
• Respiratory movement measuring instrument (RMMI, Sahlgrenska only) 
• Patient questionnaires regarding physical activity and symptoms when breathing 
(Sahlgrenska only) 
• Confirmed CTED 
• Confirmed CTEPH  
• All-cause mortality  
• Recurrent PE  
• Bleeding requiring medical attention 
• Time from treatment to first follow-up visit 
• Anticoagulation 
o Agent 
o Dose 
o Compliance 
 
Outcome-related variables at second follow-up, day 9-12 months after treatment 
• All-cause mortality and date of death 
• Lab tests: Troponin, NT-proBNP, creatinine, estimated glomerular filtration rate (eGFR)  
• Echocardiogram** (not performed in cases where findings from previous echocardiogram 
are normal to the extent that it is not required according to standard clinical practice)  
• ECG 
• Dyspnea at second follow-up visit in comparison to first follow-up 
• Functional outcome (6-minute walking test and sit-to-stand 60 test) 
• MRC (0-4) 
• Generic health-related quality of life assessment (EQ-5D)   
• Disease-specific health-related quality of life (PeMB-QoL) 
• Post venous thromboembolism functional status scale (PVFS)  
• 6-minute walk test  
• Sit-to-stand 60 test 
• Respiratory movement measuring instrument (RMMI, Sahlgrenska only) 
• Patient questionnaires regarding physical activity and symptoms when breathing 
(Sahlgrenska only) 
• Confirmed CTED 
• Confirmed CTEPH  
• All-cause mortality  
• Recurrent PE  
• Bleeding requiring medical attention 
• Time from treatment to second follow-up visit 

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• Anticoagulation 
o Agent 
o Dose 
o Compliance 
 
End of study 
• In case of study drop-out: date and reason 
 
* defined according to support chart in eCRF 
** same variables as listed under Echocardiogram in Baseline Characteristics 
 
Table 2. Study outcome variables (overview) 
Variables 
Before treat-
ment 
After treatment 
(within 72 
hours) 
At 30 days 
Follow-up visit 1 
Follow-up visit 21 
Echocardiogram 
x 
x 
 
x2 
  x2 
ECG 
x 
x 
 
x 
x 
Lab tests 
  x3 
  x3 
 
 x4 
  x4 
Vital parameters 
x 
x 
 
 
 
Patient surveys5 
 
 
 
x 
x 
6MWT & STS606 
 
 
 
x 
x 
Mortality 
 
 
x 
x 
x 
Bleeding 
 
 
x 
 
 
LOS7 
 
 
x 
 
 
1 A second follow-up visit will not be performed if findings from follow-up visit 1 are normal to 
the extent that no further follow-up is required according to standard clinical practice  
2 No echocardiogram will be performed if findings from previous echocardiogram are normal to 
the extent that it is not required according to standard clinical practice  
3 Troponin, NT-proBNP, creatinine, pH, lactate, PaO2, PaCO2 
4 Troponin, NT-proBNP, creatinine 
5 MRC, EQ-5D, PeMB-QoL, PVFS 
6 6-minute walk test and sit-to-stand 60 test 
7 Length of stay in ICU/HDU and hospital 
 
Recording of data 
An electronic Case Registration Form (eCRF), RedCAP®, will be used for data collection. All study 
data will be noted and recorded in the eCRF. 
 
General methodology  
 

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Eligible patients will be identified at each participating center by the local research team (site 
investigators, study nurse etc.) with representatives at the intervention unit and or at the unit 
where ST is given respectively. Informed oral and written consent will be obtained before inclu-
sion. Data from deceased individuals who were unable to provide consent are collected retro-
spectively from medical journals in accordance with ethical approval.  
 
Data will be collected through medical records, and subsequently anonymized, organized and 
analyzed. Collection, handling, and storage of data will be done in accordance with the General 
Data Protection Regulation (GDPR). 
 
Publishing and substudies 
 
The main study results will be published in two separate articles. The first will report findings on 
short-term outcomes (up to and including 30 days), while the second will focus on long-term 
outcomes and follow-up visits. Both articles will be submitted to peer-reviewed scientific journals 
for publication. Planned substudies will be detailed in separate documents, which will outline the 
objectives, predefined outcomes, and statistical analysis plans for each substudy. 
 
Statistical methods and sample size (will be updated in accordance with a finalized statistical 
analysis plan) 
 
Descriptive statistics will be used for group characteristics and outcomes. Intergroup compari-
sons will be done using Fisher’s exact test for dichotomous variables, Chi-square test for non-
ordered categorical variables, and the Mann-Whitney U-test for continuous variables.  
The comparative analyses between the groups considering the dichotomous study outcomes will 
be performed using logistic regression adjusted for known and statistically identified confound-
ers (variables that are related both to the study group and the outcome). Odds-ratios with asso-
ciated 95% CI, p-values and area under the receiver operating characteristic curve (AUC-ROC) will 
be presented. Hosmer-Lemeshow test will be performed as a goodness-of-fit test. 
 
The comparative analyses between the groups considering the continuous study outcomes will 
be performed using linear regression adjusted for known and statistically identified confounders. 
Model assumptions will be checked by reviewing diagnostic plots, and if needed transformation 
(e.g. log) of the outcome variable will be performed. Least square means with associated 95% CI, 
p-values and R2 will be presented.  
 
Outcome variables length of stay in ICU (hours) and length of hospital admission (days) will be 
handled as continuous variables in the case of no censored patients. In case of censored patients 
in the database, time to discharge will be studied using Cox proportional hazard model, resulting 
in hazard ratios with 95% CI and p-value. Proportional hazards assumptions will be checked 
graphically. Otherwise, the variables will be studied as continuous variables using either linear 
regression assuming normal distribution if applicable or Poisson or negative binomial regression 
depending on the distribution of the variables. Results from the Poisson and negative binomial 
regression result in relative risks with 95% CI and p-value. 

Study protocol for data acquisition in the non-interventional observational study PE-NORDIC 
Date: 250520 / Version: 1.2 
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Additionally, sensitivity analyses will be conducted applying propensity score 1:1 matching using 
the patients’ background data to estimate the propensity score, performed by using logistic re-
gression. Matching will be made applying nearest neighbor matching with the optimal caliper 
width of 0.2 of the standard deviation of the logit of the propensity score, as recommended. The 
performance will be validated by comparing the patient characteristics between the matched 
groups, that are expected not to differ. 
 
P-values ≤ 0.05 will be considered significant. All analyses will be performed using SAS software 
version 9.4 or later (SAS Institute Inc., Cary, NC, USA). 
 
Ethical approval 
Dnr 2019-00827 (approved 2019-02-04), amendments: Dnr 2022-04256-02 (approved 2022-08-
29), Dnr 2023-04750-02 (approved 2023-08-22) Dnr 2023-06931-02 (approved 2023-12-01) Dnr 
2024-00038-02 (approved 2024-01-28) Dnr 2024-04908-02 (approved 2024-09-04), 2025-00546-
02 (approved 2025-03-10) 
 
ClinicalTrials.gov: TBA 
 
Funding 
This study is supported by the Department of Anaesthesia and Intensive Care, Sahlgrenska Uni-
versity Hospital, and the following grants: Gothenburg Medical Society (GLS-1001095), The Swe-
dish Heart Lung Foundation (20240809), The Health & Medical Care Committee of the Region 
Västra Götaland (VGFOUREG-1010828). 
 
References 
(1) Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and man-
agement of acute pulmonary embolism developed in collaboration with the European Respira-
tory Society (ERS). Eur Heart J. 2020;41(4):543-603. 
(2) Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of 
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