Diagnostic Strategy for Suspected Pulmonary Embolism Based on 4PEPS

NCT ID: NCT06015529

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 2951 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-29
• Study Completion Date: 2025-09-30

Brief 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.

Detailed 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.

Conditions

Pulmonary Embolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Control group - current practices

The investigating physicians of the participating centers in the control group will be free to provide care as they see fit. However, a reminder of national and European guidelines for PE management will be given to them and they will have the recommendation to apply a validated strategy. To make it easier, the different scores will be included in the clinical help-decision support software called SPEED. Investigators will be asked to enter data about the included patients directly into SPEED, which will act as the study's electronic case report form (eCRF). A paper version of the CRF will also be available.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention group - 4PEPS strategy

Physicians of the participating centers in the intervention group will have the recommendation to apply the 4PEPS strategy. To make it easier to apply, the 4PEPS score will be included in SPEED. Investigators will be asked to enter the information relating to patients included in the study directly into SPEED before performing any testing. Entering these data will enable the 4PEPS score to be calculated automatically and specific recommendations to be provided. A paper version of the CRF will also be available

Group Type: ACTIVE_COMPARATOR

4PEPS strategy

Intervention Type: DIAGNOSTIC_TEST

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

1. based only on clinical data (very low CP: PEPS < 0),

2. based on a D-dimer level < 1000 μg/L (low CP: PEPS ≥ 0 and < 5),

3. based on a D-dimer level with an age-adjusted cut-off value (moderate CP: PEPS ≥ 5 and <12), or

4. the diagnosis cannot reliably be ruled out based on a D-dimer test (high CP: PEPS ≥ 12)

Interventions

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

1. based only on clinical data (very low CP: PEPS < 0),

2. based on a D-dimer level < 1000 μg/L (low CP: PEPS ≥ 0 and < 5),

3. based on a D-dimer level with an age-adjusted cut-off value (moderate CP: PEPS ≥ 5 and <12), or

4. the diagnosis cannot reliably be ruled out based on a D-dimer test (high CP: PEPS ≥ 12)

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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).

Exclusion Criteria

• Age < 18 years.
• Known result of a specific diagnostic imaging examination for PE (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 who objects to participating in the research (preliminary phase) or is unable to give free and informed consent (active phase).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre-Marie ROY, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Angers

Locations

Cliniques Bruxelles

Brussels, , Belgium

CHU Liège

Liège, , Belgium

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, , France

Countries

Belgium; France

References

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 Jun 1;6(6):669-677. doi: 10.1001/jamacardio.2021.0064.

Reference Type: BACKGROUND

PMID: 33656522 (View on PubMed)

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 trial. Ann Intern Med. 2009 Nov 17;151(10):677-86. doi: 10.7326/0003-4819-151-10-200911170-00003.

Reference Type: BACKGROUND

PMID: 19920268 (View on PubMed)

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&PEPS Trial. Diagnostics (Basel). 2022 Dec 9;12(12):3101. doi: 10.3390/diagnostics12123101.

Reference Type: BACKGROUND

PMID: 36553108 (View on PubMed)

Other Identifiers

36553108

Identifier Type: -

Identifier Source: org_study_id