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

Not Applicable
Completed
Conditions
Pulmonary Embolism
Interventions
Other: HESTIA
Other: sPESI
Registration Number
NCT02811237
Lead Sponsor
University Hospital, Angers
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1975
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;

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HESTIA groupHESTIA-
sPESI groupsPESI-
Primary Outcome Measures
NameTimeMethod
The rate of the composite of recurrent VTE, major bleeding and all cause death at 30 days30 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.

Secondary Outcome Measures
NameTimeMethod
The rate of "low-risk" patients in theory eligible for outpatient care (second major secondary objective)1 day

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.

Safety endpoints - Death14 days, 30 days, 90 days

The rate of all-cause death

Applicability of management strategies1 day

The rate of patients actually managed as outpatients among number of patientpatients eligible for outpatient management

Resources utilizationDay 90

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.

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))1 day

The rate of patients managed as outpatients defined by patients discharged home within 24 hours after the inclusion in the study.

Safety endpoints - Rate of cumulative events14 days, 30 days, 90 days

The rate of the composite of recurrent VTE, major bleeding and all-cause death,

Safety endpoints - Recurrent VTE14 days, 30 days, 90 days

The rate of recurrent VTE

Safety endpoints - Suspected recurrent VTE14 days, 30 days, 90 days

The rate of recurrent VTE suspicion

Safety endpoints - Major Bleeding14 days, 30 days, 90 days

The rate of major bleeding

Safety endpoints - Non major bleeding14 days, 30 days, 90 days

The rate of non-major clinically relevant bleeding

Safety endpoints - Serious adverse event14 days, 30 days, 90 days

The rate of serious adverse event as defined in good clinical practice

Patient satisfaction with care30 days

A specific questionnaire will be used at 30 days following inclusion:

- Anti-Clot Treatment - Specific Questionnaire (ACTS)

Patient quality of life30 days

A specific questionnaire will be used at 30 days following inclusion:

- Patient-reported Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL).

Trial Locations

Locations (28)

Hôpital de Namur

🇧🇪

Namur, Belgium

Red Cross Hospital

🇳🇱

Beverwijk, Netherlands

Leiden University Medical Center Leiden,

🇳🇱

Leiden, Netherlands

Cliniques Universitaires Saint-Luc

🇧🇪

Brussels, Belgium

Hôpital Erasme

🇧🇪

Bruxelles, Belgium

Hôpital Saint-Pierre

🇧🇪

Bruxelles, Belgium

CHU Brest

🇫🇷

Brest, France

CHU de Liège

🇧🇪

Liege, Belgium

Hôpital de Lausanne

🇨🇭

Lausanne, Switzerland

Hia Brest

🇫🇷

Brest, France

CHU Clermont-Ferrand

🇫🇷

Clermont-Ferrand, France

Thibault Schotté

🇫🇷

Le Mans, France

Hôpital de Genève

🇨🇭

Geneve, Switzerland

CHU de Rouen

🇫🇷

Rouen, France

CHU Saint Etienne

🇫🇷

Saint Etienne, France

CH Toulon

🇫🇷

Toulon, France

CHU Toulouse

🇫🇷

Toulouse, France

TERGOOI

🇳🇱

Hilversum, Netherlands

APHP Lariboisière

🇫🇷

Paris, France

APHP Louis Mourier

🇫🇷

Colombes, France

Angers University Hospital

🇫🇷

Angers, France

CHU Dijon

🇫🇷

Dijon, France

CHU de Montpellier

🇫🇷

Montpellier, France

APHP Hôpital Européen Georges Pompidou

🇫🇷

Paris, France

CHU Grenoble

🇫🇷

Grenoble, France

APHP Cochin

🇫🇷

Paris, France

Ramon y Cajal Hospital

🇪🇸

Madrid, Spain

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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