Hospitalization or Out-treatment ManagEment of Patients With Pulmonary Embolism: a Randomized Controlled Trial

Study Overview
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Brief Summary
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Several studies have demonstrated the possibility of outpatient management or early discharge for certain patients presenting acute pulmonary embolism (PE), providing a suitable structure is in place. The approach featured in the most recent guidelines on acute PE of the European Society of Cardiology, refers to an all-cause mortality risk assessment using the Pulmonary Embolism Severity Index (PESI) score or the simplified PESI score (sPESI). The sPESI takes into account demographics (age), patient history (cancer, cardiac or respiratory disease), and clinical data (systolic blood pressure, heart rate, oxygen saturation). Outpatient care is offered to low-risk patients, providing that all the conditions pertaining to start anticoagulant treatment and follow-up at home are met. An alternative approach based on a list of simple criteria has been developed as the one used in HESTIA study. The main criteria included in the HESTIA rule consist of absence of the following: hemodynamic instability, need for oxygen therapy, high-risk of hemorrhage, renal or liver failure, or other medical or social conditions requiring hospitalization. The investigators hereby propose comparing these two approaches in an open-label, controlled randomized international trial with blinded adjudication of endpoints. The main objective is to demonstrate, in normotensive PE patients, that a strategy based on the HESTIA rule compared to a strategy based on the simplified PESI score is at least as safe as regards the 30-day-rate of adverse events (recurrent VTE, major bleeding or death). The major secondary objectives are to demonstrate, in normotensive PE patients, that a strategy based on the HESTIA rule compared to a strategy based on the simplified PESI score is more effective : As regards the rate of patients eventually managed as outpatients. As regards the rate of patients, in theory, eligible for outpatient care,

Detailed Description
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All patients admitted in the Emergency Department of the participating centres and diagnosed with PE will be eligible and assessed for potential inclusion. Included patients will be randomized into two groups (1:1) and stratified by centre. Data will be recorded in a computerized case report form (e-CRF) enabling the randomization. The HESTIA group will receive outpatient care proposal based on HESTIA criteria. The sPESI group will receive outpatient care proposal based on the simplified PESI score. Any reason for management (hospitalization or outpatient treatment) not based on the recommendation will be explained and documented in the e-CRF. Follow-up will occur within 72 hours after inclusion, at 14 days, 1 month, and 3 months in both groups to gather clinical event data (recurrent VTE, major bleeding, death), treatment data, unscheduled hospitalizations and patient satisfaction assessment results. The major objectives will test HESTIA based strategy versus sPESI based strategy in a hierarchical approach: step 1: non-inferiority analysis on the rate of adverse events, if yes, step 2: superiority analysis on the rate of patients managed as outpatients, if yes, step3: superiority analysis on the rate of patients, in theory, eligible for outpatient care.

Official Title
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Criteria for Hospitalization or Outpatient Management of Patients With Pulmonary Embolism, Hestia Rule Versus Simplified PESI Score : an Open-label Controlled Randomized International Trial (HOME-PE)

Conditions
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Pulmonary Embolism

Intervention / Treatment
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* Other: HESTIA
* Other: sPESI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admission to Emergency Department or unscheduled consultation in one of the participating centres; Symptomatic pulmonary embolism objectively confirmed according to the European Society of Cardiology criteria Insurance cover according to local legislation; Age ≥18 years; Free informed consent according to local legislation Exclusion Criteria: Shock or hypotension defined as systolic blood pressure <90 mmHg or a systolic pressure drop by ≥40 mmHg, for >15 minutes, if not caused by new-onset arrhythmia, hypovolaemia, or sepsis; Diagnosis of pulmonary embolism established more than 24H before inclusion; More than 48h between first presentation to the Emergency unit and inclusion - - Factors rendering 30-day follow-up impossible;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HESTIA group<br> | Other: HESTIA<br>* Management based on the HESTIA rule: If the rule is negative, meaning that patient meet none of the exclusion criteria of the rule, the proposed management will be outpatient care. In the other cases, the patient will receive in-hospital care. Any reason for management (hospitalization or outpatient treatment) not based on the recommendation will be explained and documented in the e-CRF.<br>|
| Other: sPESI group<br> | Other: sPESI<br>* Management based on the simplified PESI score: If the sPESI score =0, the proposed management will be outpatient care. In the other cases, the patient will receive in-hospital care. Any reason for management (hospitalization or outpatient treatment) not based on the recommendation will be explained and documented in the e-CRF.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of the composite of recurrent VTE, major bleeding and all cause death at 30 days | Recurrent VTE: objectively confirmed pulmonary embolism or deep venous thrombosis objectively confirmed. Major bleeding: according to the International Society on Thrombosis and Haemostasis' criteria. Death: all-cause mortality. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of patients actually managed as outpatients (meaning patients discharged home within 24 hours after the inclusion in the study (first major secondary objective)) | The rate of patients managed as outpatients defined by patients discharged home within 24 hours after the inclusion in the study. | 1 day | 
| The rate of low-risk patients in theory eligible for outpatient care (second major secondary objective) | The rate of low-risk patients eligible for outpatient care: HESTIA group: patients meeting none of the exclusion criteria of the rule (HESTIA rule negative); sPESI group: patients with a simplified PESI score =0. | 1 day | 
| Safety endpoints - Rate of cumulative events | The rate of the composite of recurrent VTE, major bleeding and all-cause death, | 14 days, 30 days, 90 days | 
| Safety endpoints - Recurrent VTE | The rate of recurrent VTE | 14 days, 30 days, 90 days | 
| Safety endpoints - Suspected recurrent VTE | The rate of recurrent VTE suspicion | 14 days, 30 days, 90 days | 
| Safety endpoints - Major Bleeding | The rate of major bleeding | 14 days, 30 days, 90 days | 
| Safety endpoints - Non major bleeding | The rate of non-major clinically relevant bleeding | 14 days, 30 days, 90 days | 
| Safety endpoints - Death | The rate of all-cause death | 14 days, 30 days, 90 days | 
| Safety endpoints - Serious adverse event | The rate of serious adverse event as defined in good clinical practice | 14 days, 30 days, 90 days | 
| Applicability of management strategies | The rate of patients actually managed as outpatients among number of patientpatients eligible for outpatient management | 1 day | 
| Resources utilization | Resources utilization will be assessed via the cumulative in-hospital length of stay (LOS) defined as the LOS for initial hospitalization plus LOS of possible unscheduled hospitalizations in the 30 days and 3 months following admission. | Day 90 | 
| Patient satisfaction with care | A specific questionnaire will be used at 30 days following inclusion: - Anti-Clot Treatment - Specific Questionnaire (ACTS) | 30 days | 
| Patient quality of life | A specific questionnaire will be used at 30 days following inclusion: - Patient-reported Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL). | 30 days |