Clinical trial NCT02811237: Hospitalization or Out-treatment ManagEment of Patients With Pulmonary Embolism: a Randomized Controlled Trial
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Embolism
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: European Georges Pompidou Hospital
name: Hospital Universitario Ramon y Cajal
name: Leiden University Medical Center
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: University of Lausanne Hospitals
First posted: 2016-06-23
Enrollment: 1975
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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;

Primary outcomes:
measure: The rate of the composite of recurrent VTE, major bleeding and all cause death at 30 days
timeFrame: 30 days
Secondary outcomes:
measure: 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))
timeFrame: 1 day
measure: The rate of "low-risk" patients in theory eligible for outpatient care (second major secondary objective)
timeFrame: 1 day
measure: Safety endpoints - Rate of cumulative events
timeFrame: 14 days, 30 days, 90 days
measure: Safety endpoints - Recurrent VTE
timeFrame: 14 days, 30 days, 90 days
measure: Safety endpoints - Suspected recurrent VTE
timeFrame: 14 days, 30 days, 90 days
measure: Safety endpoints - Major Bleeding
timeFrame: 14 days, 30 days, 90 days
measure: Safety endpoints - Non major bleeding
timeFrame: 14 days, 30 days, 90 days
measure: Safety endpoints - Death
timeFrame: 14 days, 30 days, 90 days
measure: Safety endpoints - Serious adverse event
timeFrame: 14 days, 30 days, 90 days
measure: Applicability of management strategies
timeFrame: 1 day
measure: Resources utilization
timeFrame: Day 90
measure: Patient satisfaction with care
timeFrame: 30 days
measure: Patient quality of life
timeFrame: 30 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Hôpital Saint-Pierre
city: Liege
country: Belgium
facility: CHU de Liège
city: Namur
country: Belgium
facility: Hôpital de Namur
city: Angers
country: France
facility: Angers University Hospital
city: Brest
country: France
facility: Hia Brest
city: Brest
country: France
facility: CHU Brest
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Colombes
country: France
facility: APHP Louis Mourier
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: Le Mans
country: France
facility: Thibault Schotté
city: Montpellier
country: France
facility: CHU de Montpellier
city: Paris
country: France
facility: APHP Cochin
city: Paris
country: France
facility: APHP Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: APHP Lariboisière
city: Rouen
country: France
facility: CHU de Rouen
city: Saint Etienne
country: France
facility: CHU Saint Etienne
city: Toulon
country: France
facility: CH Toulon
city: Toulouse
country: France
facility: CHU Toulouse
city: Beverwijk
country: Netherlands
facility: Red Cross Hospital
city: Hilversum
country: Netherlands
facility: TERGOOI
city: Leiden
country: Netherlands
facility: Leiden University Medical Center Leiden,
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Madrid
country: Spain
facility: Ramon y Cajal Hospital
city: Geneve
country: Switzerland
facility: Hôpital de Genève
city: Lausanne
country: Switzerland
facility: Hôpital de Lausanne
Study officials:
affiliation: CHU d'Angers, France
name: Pierre-Marie ROY, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP Hôpital Européen Georges Pompidou, Paris, France
name: Olivier SANCHEZ, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center, Leiden, The Netherlands
name: Menno HUISMAN, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Ramon y Cajal, Madrid, Spain
name: David JIMENEZ, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinique Unisersitaire Saint Luc, Brussels, Belgium
name: Andréa PENALOZA, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP Hôpital Européen Georges Pompidou, Paris, France
name: Guy MEYER, MD.PhD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center Leiden, the Netherlands
name: EriK KLOK, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Vaudois
name: Olivier HUGLI
role: PRINCIPAL_INVESTIGATOR
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