Screening for Atrial Fibrillation in Pulmonary Embolism Study -SAFE-PE Study (SAFE-PE)

Screening for Atrial Fibrillation in Pulmonary Embolism Study - SAFE-PE Study

Patients with newly diagnosed pulmonary embolism and high thromboembolic risk will be randomized to screening for atrial fibrillation or standard of care using intermittent ECG registration for at least two weeks.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation; Pulmonary Embolism
• Intervention / Treatment: Device: Zenicor intermittent ECG device; Device: 5 day ECG patch

Detailed Description

Patients included in the study might be referred for an ultrasound of deep vein thrombosis unless this has already been performed. Blood will be drawn in a subset of patients to assess cardiac biomarkers, and stored in a biobank for further analysis of thrombotic biomarkers. If a computed tomography (CT) angiogram was used as diagnostic method for pulmonary embolism a radiologic review will be performed to assess presence of right atrium thrombus, with the reviewer will be blinded to the presence of atrial fibrillation (AF). In addition, an echocardiogram of the heart will be performed.

Many patients with pulmonary embolism have prolonged symptoms of dyspnoea, and palpitations. These symptoms are also described in patients with atrial fibrillation. All participants will be asked to fill out a standardized quality of life (RAND-36)-, and a symptoms questionnaire (modified European Heart Rhythm association symptom scale). Upon inclusion all patients will be reviewed for factors predisposing to PE such as recent surgery, or illness requiring immobilisation within the past three months prior to index event.

After inclusion patients will be randomised to screening for atrial fibrillation or standard of care. Participants who get randomised into the screening arm will be screened for AF using a validated, handheld ECG device at least twice daily for two weeks. Participants who get AF diagnosed during the study will be referred for appropriate cardiology follow-up and the anticoagulant therapy will be changed from a fixed time to continued (subject to yearly reviews). Patients will then be followed for five years using the Swedish death registry, and the Swedish national patient registry, in combination with the national prescription registry for the outcomes.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 182 88
    • Danderyd Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recent pulmonary embolism (within three months)

Fulfilling Chads-Vasc criteria for life-long oral anticoagulant therapy (2 points for men, and 3 points for women), or age > 65 years

Exclusion Criteria:

• Known diagnosis of atrial fibrillation Contra-indication to oral anticoagulant therapy Provoked pulmonary embolism in sub-segmental artery only Active cancer therapy (on-going therapy, recent surgery or life-expectancy below 1 year)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Arm; Standard of care
Active Comparator: Screening Arm; Screening for atrial fibrillation using a hand-held ECG device (Zenicor intermittent ECG) at least twice daily for two weeks. In patients where AF is detected prolonged OAC therapy will be administered.	Device: Zenicor intermittent ECG device; At least two weeks of screening twice daily for atrial fibrillation using intermittent ECG recordings, and prolonged use of OAC-therapy if atrial fibrillation is detected; Other Names: Oral anticoagulant therapy prolonged (if AF detected); Device: 5 day ECG patch; Selection of device for monitoring clinicians' choice; Other Names: Oral anticoagulant therapy prolonged if AF detected

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality in the screening arm compared to the control arm	5 years after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality and thromboembolic events	Combined endpoint of mortality and thromboembolic events (stroke, transient ischemic attack, systemic embolism, deep vein thrombosis and pulmonary embolism) in the screening arm compared to the control arm	5 years after intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life using RAND-36	All patients will fill in a quality of life questionnaire (RAND-36). Quality of life will be compared in patients where AF is detected compared to the group where AF is not detected in patients with PE. Quality of life will be measured using a RAND-36 questionnaire that uses questions regarding physical, mental and social wellbeing based on the World Health Organization's definition of health.	1 year after inclusion
Quality of life using EHRA symptom scale	Quality of life will be compared in patients where AF is detected compared to the group where AF is not detected. Quality of life will be measured using a modified European Heart Rhythm association (EHRA) symptom scale and reported as a separate outcome.	1 year after inclusion
Assessment of clinical risk factors for atrial fibrillation in patients with pulmonary embolism	Comparison of clinical characteristics (diagnosis of prior hypertension, diabetes mellitus type 2, vascular disease, heart failure, stroke/TIA) to identify risk factors for detection of AF in patients with PE, and use to build a risk score for AF detection. Patients in the intervention arm who had atrial fibrillation discovered after screening with intermittent ECG will be compared to participants in the intervention arm where atrial fibrillation was not discovered. Multivariable logistic regression will be used to determine which risk factors are most important in order to detect previously undetected AF in patients with pulmonary embolism.	1 year after inclusion
Biomarkers as a prediction of diagnosis in pulmonary embolism	The use of biomarkers to predict risk of future thromboembolic events and mortality in patients with PE. Blood will be collected from the majority of participants in the stuydy and stored in a biobank. Different biomarkers will be measured (for instance NT-proBNP, troponin, CRP and thromboembolic biomarkers) and the association between the levels of biomarkers and mortality, and thromboembolic morbitidy will be analysed using Cox proportional regression models.	5 years after inclusion
The association between biomarkers and newly detected AF in patients with pulmonary embolism	Biomarkers will be collected in the majority of patients. The levels of various biomarkers in the intervention group where AF was detected will be compared to participants in the intervention group where AF was not detected. Multivariable logistic regression will be used to study the association between biomarkers and the detection of AF in patients with PE.	1 years after inclusion
Echocardiographic measures and their association with outcome in patients with PE	Various echocardiographic parameters will be measured in all included patients. The echocardiographic measures in patients in the study who had a secondary outcome will be compared to patients who did not have a secondary outcome. Echocardiographic measures will be analysed using multivariable Cox regression analysis in order to find parameters that are associated with poor outcome.	5 years after inclusion
Echocardiographic parameters and their association with newly detected AF in patients with PE	In the intervention arm echocardiographic parameters will be compared for the group where AF was detected compared to the group where AF was not detected. Using multivariable logistic regression echocardiographic variables associated with the detection of atrial fibrillation in patients with pulmonary embolism will be studied.	1 years after inclusion
Presence of right atrial thrombus on DT angiography in PE	In participants where DT angiography was used in order to diagnose PE the images will be reviewed in order assess whether a right atrial thrombi could be detected. The outcome between participants with right atrial thrombus on DT angiography will be compared to participants who did not have right atrial thrombus on DT.	5 years after inclusion

Collaborators and Investigators

• Sponsor: Danderyd Hospital
• Collaborators: Karolinska Institutet
• Investigators: Study Director: Håkan Wallén, MD PhD, Karolinska Institutet - Danderyd Hospital; Principal Investigator: Emma Svennberg, MD PhD, Karolinska Institutet - Danderyd Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: August 24, 2017
• First Submitted That Met QC Criteria: September 3, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Screening; Pulmonary embolism
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Arrhythmias, Cardiac; Embolism; Atrial Fibrillation; Pulmonary Embolism; Anticoagulants
• Other Study ID Numbers: SAFE-PE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No