Point-of-care Ultrasound in Suspected Pulmonary Embolism

Point-of-care Ultrasound in the Diagnostic Work-up of Suspected Pulmonary Embolism - a Multicenter Randomized Controlled Trial

Pulmonary embolism (PE) is a common cardiovascular condition with an estimated incidence of 0.60 to 1.12 per 1000 inhabitants in the United States of America, and the diagnosis is challenging as patients with PE present with a wide array of symptoms.

Computed tomography pulmonary angriography (CTPA) and lung ventilation-perfusion scintigraphy (VQ) are considered the gold-standards in PE-diagnostics but may not always be feasible. CTPA is contraindicated by contrast allergy or renal failure and both modalities require involvement of multiple staff-members and transport of the patient. Lung scintigraphy cannot be performed in an emergency situation, with unstable patients and patients unable to comply to the examination.

Ultrasound represent a possible tool in confirming or dismissing clinical PE suspicion. Ultrasound is non-invasive and can be performed bedside by the clinician, an approach known as point-of-care ultrasound (PoCUS), reducing both time, radiation-exposure and costs.

The aim of this study is to investigate whether integrating cardiac, lung and deep venous ultrasound in the clinical evaluation of suspected PE reduces the need for referral to CTPA or lung scintigraphy, during emergency department work up, while maintaining safety standards.

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism; Pulmonary Embolus/Emboli
• Intervention / Treatment: Diagnostic test: Point-of-care-ultrasound examination

Detailed Description

All ultrasound examinations will be performed by a physician certified in ultrasound by the Danish Society for Emergency Physicians in accordance with the Danish Health Agency.

Based on ultrasonographic findings, PE suspicion is allocated to one of three categories:

1. Clinical suspicion of PE confirmed if ≥1 of the following ultrasound findings:

1. Visible proximal deep venous thrombus
2. ≥2 hypoechoic subpleural lung consolidations with a diameter of ≥0,5cm
3. Visible right ventricular thrombus
4. McConnell's sign if no known pulmonary hypertension, interstitial lung disease, COPD or pulmonary valve disease
5. D-sign present in both systole and diastole if no known pulmonary hypertension, interstitial lung disease, COPD or pulmonary valve disease

If PE is confirmed by ultrasound, the physician will apply the simplified pulmonary embolism severity index score (sPESI) and estimate risk of mortality within 30 days based on clinical signs and symptoms, cardiac troponin level and RV dysfunction. Patients with intermediate-high or high risk, requiring admission to a cardiology department will be referred for CTPA. Patients with low or intermediate-low risk, not requiring admission, will be discharged with anticoagulative treatment.

A thorough presentation of the sPESI-score and early mortality risk assessment is available in the 2019 collaborative guidelines by the ERS and ESC on the diagnosis and management of PE.

2. Further diagnostic imaging (CTPA or V/Q) required if ≥1 of the following ultrasound findings:

1. 1 hypoechoic subpleural lung consolidation with a diameter of ≥0,5cm
2. Pleural effusion not explained by other cause
3. Basal RVEDD/LVEDD >1.0 or an RV visibly larger than the LV
4. TAPSE <17 mm
5. No deep venous thrombus, no lung consolidation or effusion, no signs of RV strain or thrombus but strong clinical suspicion.
6. McConnell's or D-sign in the presence of known pulmonary hypertension, interstitial lung disease, COPD or pulmonary valve disease

If PE suspicion can be neither dismissed nor confirmed after ultrasound investigation, the patient will be referred to further investigation as usual with CTPA or lung scintigraphy. Subsequent plan will be in accordance with department guidelines.

3. Clinical suspicion of PE dismissed if ≥1 of the following ultrasound findings:

1. No deep venous thrombus, no lung consolidation or effusion, no signs of RV strain or thrombus and a plausible differential diagnosis or low clinical suspicion
2. Obvious differential diagnosis demonstrated on ultrasound (i.e., pneumonia, pneumothorax, interstitial syndrome, left sided heart failure)

If PE suspicion is dismissed by ultrasound investigation, the patient will be either discharged or subject to further investigations in accordance with department guidelines if indicated.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Casper Falster, MD; Phone Number: +4560139562; Email: casper.falster@rsyd.dk

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Esbjerg Hospital
  • Kolding, Denmark, 6000
    • Kolding Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital
  • Slagelse, Denmark, 4200
    • Slagelse Hospital
  • Svendborg, Denmark, 5700
    • Svendborg Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Referred or Admitted to an emergency department
• Clinical suspicion of PE raised by physician requiring further diagnostic imaging (Well's score 0-6 with elevated age-adjusted D-dimer or Wells score >6 regardless of D-dimer)

Exclusion Criteria:

• Refusal of informed consent
• Pregnancy
• Permanent mental disability
• Age <18 years
• Diagnosis of PE within the last 6 months
• Hemodynamic instability (systolic blood pressure <90 mmHg for at least two consecutive measurements)
• Ultrasound of heart, lungs or deep veins performed prior to enrollment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PoCUS group; Patients allocated to the PoCUS investigation arm will receive an ultrasound investigation resulting in either confirmation or dismissal of pulmonary embolism suspicion or requiring CTPA or VQ	Diagnostic test: Point-of-care-ultrasound examination; The intervention consists of three ultrasound modalities: Cardiac ultrasound assessing signs of right ventricular strain or other obvious pathology.; Deep venous ultrasound assessing presence of a deep venous thrombus; Lung ultrasound assessing presence of pulmonary infarctions, pleural effusion, pneumothorax or interstitial syndrome.
No Intervention: Control group; Patients allocated to the control group will continue with CTPA or VQ without PoCUS investigation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients referred to CTPA or VQ after multiorgan PoCUS	Up to 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events in the intervention and control group after inclusion, including readmission, serious bleeding or death	3 months
Number of hours until initiation of relevant treatment after clinical evaluation in the control and intervention group.	Up to 24 hours
Proportion of included patients diagnosed with PE in the control and intervention group	Up to 24 hours
Proportion of patients diagnosed with alternative diagnosis following clinical evaluation in the intervention and control group	Up to 24 hours
Proportion of patients in the intervention and control group discharged to their own home following clinical evaluation	Up to 24 hours
Proportion of patients in the reference and control group admitted to a cardiology department for telemetry monitoring (i.e. high risk PE) following clinical evaluation.	Up to 24 hours
Proportion of patients in the reference and control group admitted to an intensive care unit following clinical evaluation	Up to 24 hours
Proportion of patients in the reference and control group referred to supplementary CTPA or lung scintigraphy within 30 days after inclusion	30 days
Total costs related to diagnostic work up and hospital stay as assessed by HEAT 4.2	Up to 1 year
Number of subsequent cancer diagnosis in the intervention and control group within 3 months of inclusion	3 months

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Southern Denmark; Odense Patient Data Explorative Network; Snedkermester Sophus Jacobsen and hustru Astrid Jacobsens Foundation
• Investigators: Principal Investigator: Casper Falster, MD, Odense University Hospital; Study Chair: Christian B Laursen, Prof. MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: April 12, 2021
• First Submitted That Met QC Criteria: May 8, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Ultrasound; Diagnosis; Ultrasonography; Echocardiography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: PulmonaryEmbolismPoCUSOdense

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
• product manufactured in and exported from the U.S.: No