Non-invasive Diagnosis of Pulmonary Embolism by Use of Biomarkers in Exhaled Breath Condensate

In this study, a new, non-invasive method for diagnosis of pulmonary embolism (PE) will be tested. In pre-clinical studies, we have identified 151 putative biomarkers for pulmonary embolism in the exhaled breath condensate (EBC). These biomarkers needs validation/consolidation in a clinical setting before further test of this new diagnostic method.

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Diagnostic test: Test of biomarkers for PE in EBC

Detailed Description

The study will compare the protein profiles of EBC collected from patients admitted to the department of cardiology with suspected pulmonary embolism and controls with same age (within a range of 10 years) and gender from the outpatient clinic awaiting elective cardiovascular surgery. The main-outcome (i.e. means of the relative amounts of specific proteins in the EBC samples) will be compared by unpaired t-tests after assessment of normality and standard deviations within the three groups (PE confirmed, PE suspected but not confirmed and controls). Furthermore, sensitivity and specificity will be calculated for relevant proteins. The results from analysis of EBC samples from the patients and controls will be compared with results from the porcine model in order to confirm and reduce the number of putative biomarkers for PE. Blood samples (i.e. excess plasma from routine blood samples drawn as a part of routine diagnostic work-up) from the study participants will be stored for standardization of the putative markers and verification and supplementing analysis of the EBC markers. In order to qualify the most suitable markers and substrates for standardization, the analysis of the EBC samples must be completed before the blood samples can be analyzed. Only biochemical, no genetic analysis will be conducted.

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

It is expected that

• 40 patients with confirmed PE,
• 40 patients with suspected PE, but where diagnostic work-up did not confirm PE and
• 40 healthy controls

will be included in the study over a six-month period.

Description

Inclusion Criteria - Suspected/confirmed PE patients:

• Admitted to the emergency department with initial diagnosis of PE, visited to the Department of Cardiology at Aalborg University Hospital.
• Are conscious and able to understand the given study information.
• Possess legal capacity.
• Age above 18 years.
• Informed, signed consent is obtained.
• Clinically stable, which is defined as patients with stable blood pressure and not in need for other treatments .
• No need for organ support, which comprises need for vasopressors or inotropes, mechanical ventilation, extra corporal circulation or renal replacement therapy.

Inclusion Criteria - Controls:

• Patients as the PE patients, but where the diagnosis of PE is rejected.

The rest of the control persons will be recruited as described:

• Patients who are going to have elective procedures at the Department of Cardiology, Aalborg University Hospital.
• Same gender and age (within a 10-year range) as an included PE patient.
• Are conscious and able to understand the given study information.
• Possess legal capacity.
• Age above 18 years.
• Informed, signed consent is obtained.

Exclusion Criteria:

• Active malignant disease (i.e. ongoing anti-cancer therapy or palliation).
• Current smokers

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PE confirmed; Patients admitted with confirmed pulmonary embolism.	Diagnostic test: Test of biomarkers for PE in EBC; New method for diagnosis of pulmonary embolism (PE) in order to validate/consolidate 151 putative identified biomarkers for PE in the exhaled breath condensate (EBC). The EBC will be collected by use of the RTube(R) system which has been used in previous studies of EBC. As the patient breathes through a mouth piece, the exhaled breath is led through a cooling chamber where the vaporous part of the exhaled breath condenses. We aim at collecting a total minimum of 3.0 mL EBC per study subject in order to have a sufficient amount of protein for the subsequent analysis. We aim at collecting exhaled breath condensate for 2*15 minutes with the possibility to stop the collection after less than 15 minutes if the volume is sufficient.
PE suspected; Patients admitted with suspected, but not confirmed pulmonary embolism.	Diagnostic test: Test of biomarkers for PE in EBC; New method for diagnosis of pulmonary embolism (PE) in order to validate/consolidate 151 putative identified biomarkers for PE in the exhaled breath condensate (EBC). The EBC will be collected by use of the RTube(R) system which has been used in previous studies of EBC. As the patient breathes through a mouth piece, the exhaled breath is led through a cooling chamber where the vaporous part of the exhaled breath condenses. We aim at collecting a total minimum of 3.0 mL EBC per study subject in order to have a sufficient amount of protein for the subsequent analysis. We aim at collecting exhaled breath condensate for 2*15 minutes with the possibility to stop the collection after less than 15 minutes if the volume is sufficient.
Controls; Healthy controls same gender and age (within af range of 10 years) as PE patients	Diagnostic test: Test of biomarkers for PE in EBC; New method for diagnosis of pulmonary embolism (PE) in order to validate/consolidate 151 putative identified biomarkers for PE in the exhaled breath condensate (EBC). The EBC will be collected by use of the RTube(R) system which has been used in previous studies of EBC. As the patient breathes through a mouth piece, the exhaled breath is led through a cooling chamber where the vaporous part of the exhaled breath condenses. We aim at collecting a total minimum of 3.0 mL EBC per study subject in order to have a sufficient amount of protein for the subsequent analysis. We aim at collecting exhaled breath condensate for 2*15 minutes with the possibility to stop the collection after less than 15 minutes if the volume is sufficient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of pulmonary embolism by use of biomarkers in the EBC	The primary outcome is prediction of pulmonary embolism by use of one or more novel biomarkers in the EBC.	1-2 years

Collaborators and Investigators

• Sponsor: Aalborg University Hospital
• Collaborators: University of Aarhus
• Investigators: Principal Investigator: Inger L Gade, MD, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Actual): May 30, 2020
• Study Completion (Actual): May 31, 2020

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 4, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: ILG-PE-2018; #0053310 (Other Grant/Funding Number: The Novo Nordisk Foundation); N-20180086 (Other Identifier: Den Videnskabsetiske Komite for Region Nordjylland)

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