Modified Strategy to Safely Rule Out Pulmonary Embolism in the Emergency Department

NCT04032769 | Completed

• 1 other identifier: APHP180595
• Study Type: interventional
• Target: 1,414
• Locations: 2 countries
• Sites: 2

Brief Summary

Because a missed PE could be potentially lethal, several researches reported that PE is both overinvestigated and overdiagnosed. The diagnostic gold standard for PE is the computed tomographic pulmonary angiogram (CTPA) and has been shown to have clear risks and other downsides. To limit the use of CTPA, two rules were recently reported to be safe to exclude PE: the PERC rule and the YEARS rule. PERC is an 8 item block of clinical criteria that has recently been validated to safely exclude PE in low risk patients. YEARS is a clinical rule that allow to raise the threshold of D-dimer for the order of CTPA. However, whether a modified diagnostic algorithm that includes these two rules combined could safely reduce imaging study use in the ED is unknown. This is a non-inferiority, cluster cross-over randomized, international trial. Each center will be randomized on the sequence of period intervention: 4 months intervention (MOdified Diagnostic Strategy: MODS) followed by 4 months control (usual care), or 4 months control followed by 4 months intervention with 1 month of "wash-out" between the two periods. All centers will recruit adult emergency patients with a suspicion of PE. In the control group (usual strategy), patients will be tested for D-dimer, followed if positive by a CTPA. In the intervention group (MODS) : All included patients will be tested with quantitative D-dimer. The MODS work-up will be based on YEARS rule : \- If all YEARS criteria are absent, the threshold of D-Dimer for ordering a CTPA will be raised. If at least one criterion of YEARS is present, then the D-dimer threshold for ordering a CTPA will be as usual.

Conditions

Pulmonary Embolism

Keywords

Pulmonary embolism; PERC Rule; Years Rule; Peps Rule; Emergency department

Outcome Measures

Primary Outcomes (1)

• the failure percentage of the diagnostic strategy, defined as a diagnosed thrombo-embolic event at 3 month follow-up

  existence of a diagnosed thrombo embolic event (PE or DVT) among patients in whom PE has been initially ruled out.

  3 months follow up

Secondary Outcomes (8)

• reduced irradiative imaging studies

  3 months follow up

• ED length of stay

  Through ED Discharge within 24 hours

• anticoagulant therapy administration

  3 months follow up

• hospital admission

  3 months follow up

• hospital re admission

  3 months

Study Arms (2)

Modified strategy MODS

EXPERIMENTAL

the threshold of D-dimer will depend on the YEARS rule (MODS strategy): 1. If all the three items of YEARS are negative (i.e. No hemoptysis, No clinical sign of deep venous thrombosis and PE is not the most likely diagnosis), then the threshold of D-dimer will be raised at 1000 ng/ml. 2. If at least one item of YEARS is positive, then the threshold will remain unchanged ("\>500 ng/ml" for patients aged \< 50 and "\> agex10" for patients aged 50 and over). * A positive result of D-dimer and the absence of other obvious cause for PE will mandate a CTPA, or V/Q scan if CTPA is contra-indicated. * A negative result of D-dimer will rule out PE.

Other: MODS (MOdified Diagnostic Strategy)

Control group

NO INTERVENTION

All included patients will be tested with D-Dimer, threshold for ordering a CTPA as usual

Interventions

MODS (MOdified Diagnostic Strategy) OTHER

Modified diagnostic strategy (MODS): All included patients will be tested with quantitative D-dimer. The MODS work-up strategy will be based on YEARS rule, that included three criteria (hemoptysis, signs of DVT, PE is the most likely diagnosis) \- If all YEARS criteria are absent, the threshold of D-Dimer for ordering a CTPA will be raised at 1000 ng/ml. If at least one criterion of YEARS is present, then the D-dimer threshold for ordering a CTPA will be as usual (500 ng/ml, or agex10 for patients aged 50 and over)

Modified strategy MODS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient aged ≥ 18 years that presents to an ED
• With new onset of or worsening of shortness of breath or chest pain or syncope

You may not qualify if:

• Opposition to the participation to the study
• Anticipated inability to follow up at 3 month
• Other obvious cause than PE for chest pain, syncope or dyspnea
• High clinical probability of PE (estimated by the physician gestalt as \> 50%) or low clinical probability and PERC negative patients
• Low clinical probability (estimated by the physician gestalt as \< 15%) and no item of the PERC score (heart rate \> 100, Sa02 \< 95, unilateral leg swelling, hemoptysis, past history of thrombo-embolism, exogen estrogen intake, recent trauma or surgery, age ≥ 50)
• Acute severe presentation (clinical signs of respiratory distress, hypotension, SpO2\<90%, shock)
• Concurrent anticoagulation treatment
• Current diagnosed thrombo-embolic event (in the past 6 months)
• Prisoners
• Pregnancy
• No social security
• Participation in another intervention trial

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Emergency department Hospital Pitié-Salpêtrière

Paris, 75013, France

Location

Emergency department

Barcelona, Spain

Location

Related Publications (3)

• Nze Ossima A, Ngaleu Siaha BF, Mimouni M, Mezaour N, Darlington M, Berard L, Cachanado M, Simon T, Freund Y, Durand-Zaleski I. Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI). BMC Emerg Med. 2023 Nov 29;23(1):140. doi: 10.1186/s12873-023-00910-x.

  PMID: 38030975 DERIVED

• Freund Y, Chauvin A, Jimenez S, Philippon AL, Curac S, Femy F, Gorlicki J, Chouihed T, Goulet H, Montassier E, Dumont M, Lozano Polo L, Le Borgne P, Khellaf M, Bouzid D, Raynal PA, Abdessaied N, Laribi S, Guenezan J, Ganansia O, Bloom B, Miro O, Cachanado M, Simon T. Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism: A Randomized Clinical Trial. JAMA. 2021 Dec 7;326(21):2141-2149. doi: 10.1001/jama.2021.20750.

  PMID: 34874418 DERIVED

• Philippon AL, Dumont M, Jimenez S, Salhi S, Cachanado M, Durand-Zaleski I, Simon T, Freund Y. MOdified DIagnostic strateGy to safely ruLe-out pulmonary embolism In the emergency depArtment: study protocol for the Non-Inferiority MODIGLIANI cluster cross-over randomized trial. Trials. 2020 Jun 3;21(1):458. doi: 10.1186/s13063-020-04379-y.

  PMID: 32493383 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism; Emergencies

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yonathan Freund, professor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2019
• First Posted: July 25, 2019
• Study Start: October 1, 2019
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (1); ES (1)