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Diagnostic Strategy for Suspected Pulmonary Embolism Based on 4PEPS (SPEED&PEPS)

Primary Purpose

Pulmonary Embolism

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
4PEPS strategy
Sponsored by
University Hospital, Angers
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Pulmonary Embolism focused on measuring Pulmonary Embolism, suspected PE, diagnostic strategy, clinical probability, cluster-randomized trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    No Intervention

    Active Comparator

    Arm Label

    Control group - current practices

    Intervention group - 4PEPS strategy

    Arm Description

    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.

    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

    Outcomes

    Primary Outcome Measures

    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.
    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.

    Full Information

    First Posted
    July 31, 2023
    Last Updated
    August 28, 2023
    Sponsor
    University Hospital, Angers
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06015529
    Brief Title
    Diagnostic Strategy for Suspected Pulmonary Embolism Based on 4PEPS
    Acronym
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    December 2026 (Anticipated)
    Study Completion Date
    December 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital, Angers

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Embolism
    Keywords
    Pulmonary Embolism, suspected PE, diagnostic strategy, clinical probability, cluster-randomized trial

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Pragmatic cluster-randomized trial
    Masking
    None (Open Label)
    Masking Description
    blinded adjudication committee assessing endpoints
    Allocation
    Randomized
    Enrollment
    2560 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Control group - current practices
    Arm Type
    No Intervention
    Arm Description
    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.
    Arm Title
    Intervention group - 4PEPS strategy
    Arm Type
    Active Comparator
    Arm Description
    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
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    4PEPS strategy
    Intervention Description
    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)
    Primary Outcome Measure Information:
    Title
    Rate of serious clinical events in the 90 days following inclusion
    Description
    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.
    Time Frame
    90 days
    Title
    Rate of diagnostic thoracic imaging
    Description
    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.
    Time Frame
    up to 72 hours following inclusion
    Secondary Outcome Measure Information:
    Title
    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
    Description
    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.
    Time Frame
    90 days
    Title
    Rate of thromboembolic events occurring in the 90 days following inclusion in patients for whom PE was ruled out in both groups
    Description
    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.
    Time Frame
    90 days
    Title
    Rate of D-dimer measurement
    Description
    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.
    Time Frame
    up to 72 hours following inclusion
    Title
    Length of stay in ED
    Description
    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.
    Time Frame
    Up to Emergency Department discharge (assessed up to 48 hours)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pierre-Marie ROY, MD, PhD
    Phone
    +33241353637
    Email
    PMRoy@chu-angers.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Anthea LOIEZ
    Phone
    +33241353637
    Email
    Anthea.Loiez@chu-angers.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pierre-Marie ROY, MD, PhD
    Organizational Affiliation
    University Hospital, Angers
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Anonymized raw data on individual patients constituting the basis of the analysis, results and conclusions will be available to a third-party auditor and to researchers on reasonable and justified request to the main investigator (Prof. Pierre-Marie ROY - PMRoy@chu-angers.fr) after publication and approval by the study steering committee.
    IPD Sharing Time Frame
    The study protocol is already published and available (doi: 10.3390/diagnostics12123101). The other supporting documents will be available within publication of the results of the trial.
    IPD Sharing Access Criteria
    Request to the main investigator (Prof. Pierre-Marie ROY - PMRoy@chu-angers.fr)
    Citations:
    PubMed Identifier
    33656522
    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 Jun 1;6(6):669-677. doi: 10.1001/jamacardio.2021.0064.
    Results Reference
    result
    PubMed Identifier
    19920268
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    36553108
    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&PEPS Trial. Diagnostics (Basel). 2022 Dec 9;12(12):3101. doi: 10.3390/diagnostics12123101.
    Results Reference
    result

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    Diagnostic Strategy for Suspected Pulmonary Embolism Based on 4PEPS

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