Diagnostic Strategy for Suspected Pulmonary Embolism Based on 4PEPS

Pulmonary Embolism Clinical Trial

— SPEED&PEPS  

Official title:

Diagnostic Strategy for Suspected Pulmonary Embolism in Emergency Departments Based on the 4-Level Pulmonary Embolism Clinical Probability Score: SPEED&PEPS Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06015529
• Other study ID #: 36553108
• Status: Recruiting
• Phase: N/A
• Start date: November 29, 2023
• Est. completion date: May 2025

Study information

• Verified date: April 2024
• Source: University Hospital, Angers
• Contact: Pierre-Marie ROY, MD, PhD
• Phone: +33241353637
• Email: PMRoy[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The increased use of diagnostic imaging and especially computed tomography pulmonary angiography in patients suspected of pulmonary embolism (PE) is an important point of concerns. The goal of this pragmatic cluster-randomized trial is to compare the diagnostic strategy based on the four-level pulmonary embolism probability score (4PEPS) and current practices. The main questions it aims to answer is: "Does the diagnostic strategy based on 4PEPS significantly reduce the use of thoracic imaging without increasing the risk of serious adverse events as compared to current diagnostic practices?" Patients suspected of having PE in the participating emergency departments will be included and followed for 90 days. In ten centers, the emergency physicians will apply the 4PEPS strategy and in ten other centers, the emergency physicians will be free to do as they see fit. Researchers will compare the two groups of patients to see if the rate of diagnostic thoracic imaging tests and the rate of adverse events related to diagnostic strategies will differ.

Description:

Several strategies have been devised to safely limit the use of thoracic imaging in patients suspected of pulmonary embolism (PE). However, they are based on different rules for clinical probability (CP) assessment, rendering their combination difficult. The four-level pulmonary embolism probability score (4PEPS) allows the combination of all other strategies using a single CP assessment. Methods and analysis: SPEED&PEPS is a pragmatic cluster-randomized trial. After a preliminary period aimed to assess the possibility of inclusions and current practices in 23 Emergency Departments (ED), 20 EDs will be selected to participate to the active phase and randomization. Half of the centers will be allocated to the control group where physicians will be free to do as they see fit but they will be given the recommendation to apply a validated strategy. Half of the centers will be allocated to the interventional group where the physicians will be given the recommendation to apply the 4PEPS strategy. Patients with suspected PE will be included and followed for 90 days (anticipated number of patients to be included: 2560, 1280 in each arm). The primary objective will be to demonstrate that the application of the 4PEPS strategy by emergency physicians, in comparison to current practices, (i) does not increase the risk of serious events related to diagnostic strategies and (ii) significantly reduces the use of thoracic imaging. If successful, the SPEED&PEPS trial will have an important impact for patients suspected of PE limiting their irradiation and for public health in substantial savings in terms of the direct cost of diagnostic investigations and the indirect cost of hospitalizations due to waiting times or delayed harmful effects. Funding: This work is funded by a French Public Health grant (PREPS-N 2019). The funding source plays no role in the study design, data collection, analysis, interpretation or the writing of the manuscript.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2560
• Est. completion date: May 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Admission to an emergency department participating in the study.
• Suspected PE due to thoracic symptoms (dyspnea, chest pain, or hemoptysis) and/or syncope without any other obvious explanation after clinical examination and possible additional first-line tests (ECG, chest X-ray, or routine lab work-up not including D-dimer test).
• Free, prior, and informed consent to participate in the study.

Exclusion Criteria:

• Age < 18 years.
• Known result of a specific diagnostic examination for PE (D-dimer test, thoracic CT angiography, pulmonary scintigraphy, or venous ultrasound of the lower limbs).
• Hemodynamic instability (systolic blood pressure < 90 mmHg or more than 40 mmHg lower than usual for more than 15 min).
• Curative dose of anticoagulant in place for more than two days prior to inclusion.
• Pregnant or parturient patient.
• Patient in detention by judicial or administrative decision.
• Patient undergoing compulsory psychiatric treatment.
• Patient placed under a legal protection measure.
• Patient incapable of giving free and informed consent.

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Diagnostic Test:
• 4PEPS strategy
Physicians of the participating centers in the intervention group will have the recommendation to apply the 4PEPS strategy. Using 12 variables, 4PEPS defines four levels of CP that rule out a PE, namely based only on clinical data (very low CP: PEPS < 0), based on a D-dimer level < 1000 µg/L (low CP: PEPS = 0 and < 5), based on a D-dimer level with an age-adjusted cut-off value (moderate CP: PEPS = 5 and <12), or the diagnosis cannot reliably be ruled out based on a D-dimer test (high CP: PEPS = 12)

Locations

Country	Name	City	State
Belgium	Cliniques Bruxelles	Bruxelles
Belgium	CHU Liège	Liège
France	CH Agen	Agen
France	CHU Angers	Angers
France	CH Argenteuil	Argenteuil
France	CH Arpajon	Arpajon
France	AP HP Clamart	Clamart
France	CHU Clermont Ferrand	Clermont-Ferrand
France	CHU Grenoble	Grenoble
France	CH La Rochelle	La Rochelle
France	CH Versailles	Le Chesnay
France	CHU Limoges	Limoges
France	CHU Lyon	Lyon
France	CHR Metz Thionville	Metz
France	CHU Nantes	Nantes
France	CHU Nice	Nice
France	GH Paris	Paris
France	CHU Poitiers	Poitiers
France	CH Rochefort	Rochefort
France	CHU Rouen	Rouen
France	CHU Toulouse	Toulouse
France	CHU Tours	Tours
France	CH Troyes	Troyes

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Countries where clinical trial is conducted

Belgium,  France, 

References & Publications (3)

Roy PM, Durieux P, Gillaizeau F, Legall C, Armand-Perroux A, Martino L, Hachelaf M, Dubart AE, Schmidt J, Cristiano M, Chretien JM, Perrier A, Meyer G. A computerized handheld decision-support system to improve pulmonary embolism diagnosis: a randomized t — View Citation

Roy PM, Friou E, Germeau B, Douillet D, Kline JA, Righini M, Le Gal G, Moumneh T, Penaloza A. Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing. JAMA Cardiol. 2021 — View Citation

Roy PM, Moumneh T, Penaloza A, Schmidt J, Charpentier S, Joly LM, Riou J, Douillet D. Diagnostic Strategy for Suspected Pulmonary Embolism in Emergency Departments Based on the 4-Level Pulmonary Embolism Clinical Probability Score: Study Protocol of SPEED — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of serious clinical events in the 90 days following inclusion	The primary safety endpoint will be the rate of serious clinical events in the 90 days following inclusion: • Serious adverse events related to diagnostic testing (leading to hospitalization or prolongation of hospitalization, permanent inability or incapacity, and death). • Symptomatic thromboembolic events in patients not diagnosed with PE in the emergency department or new thromboembolic events in patients diagnosed with PE. • Death related to PE (initial or recurrent PE). • Major bleeding related to an anticoagulant treatment prescribed for pulmonary embolism according to ISTH criteria.	90 days
Primary	Rate of diagnostic thoracic imaging	The primary efficacy endpoint will be the rate of thoracic imaging among all included patients with suspected PE. The following examinations are considered if they are performed at the request of the emergency physician in search of PE: computed tomography pulmonary angiography (CTPA), planar perfusion or perfusion-ventilation scintigraphy, and SPECT scintigraphy.	up to 72 hours following inclusion
Secondary	Rate of thromboembolic events occurring in the 90 days following inclusion in patients for whom PE was ruled out according to the 4PEPS strategy in the intervention group	The first secondary objective is to demonstrate, in the intervention group, that the risk of false-negative diagnosis with the 4PEPS strategy is very low in accordance with the International Society of Thrombosis and Hemostasis (ISTH) criteria for validation of rule-out PE diagnostic strategies.; The endpoint will be the false-negative rate defined as the rate of thromboembolic events occurring in the 90 days following inclusion in patients in the intervention group for whom PE was ruled out according to the 4PEPS strategy and who were not treated with anticoagulants.	90 days
Secondary	Rate of thromboembolic events occurring in the 90 days following inclusion in patients for whom PE was ruled out in both groups	The second secondary objective is to demonstrate that the 4PEPS strategy (intervention group) is not inferior to current practices (control group) as regards the risk of false-negative diagnosis.; The false-negative rate will be defined as the rate of thromboembolic events occurring in the 90 days following inclusion in patients for whom PE was ruled out and who were not treated with anticoagulants.	90 days
Secondary	Rate of D-dimer measurement	The third secondary objective is to to evaluate and compare to usual practice the impact of the 4PEPS strategy as regards the rate of D-dimer measurement.	up to 72 hours following inclusion
Secondary	Length of stay in ED	The fourth secondary objective is to evaluate and compare to usual practice the impact of the 4PEPS strategy as regards the length of time spent in the emergency department by patients with suspected PE.	Up to Emergency Department discharge (assessed up to 48 hours)