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

NCT ID: NCT02811237

Last Updated: 2019-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1975 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-10-30

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.

Conditions

Pulmonary Embolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

HESTIA group

Group Type: OTHER

HESTIA

Intervention Type: OTHER

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.

sPESI group

Group Type: OTHER

sPESI

Intervention Type: OTHER

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.

Interventions

HESTIA

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.

Intervention Type: OTHER

sPESI

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.

Intervention Type: OTHER

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Georges Pompidou Hospital

OTHER

Sponsor Role: collaborator

Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

University of Lausanne Hospitals

OTHER

Sponsor Role: collaborator

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre-Marie ROY, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

CHU d'Angers, France

Olivier SANCHEZ, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

APHP Hôpital Européen Georges Pompidou, Paris, France

Menno HUISMAN, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center, Leiden, The Netherlands

David JIMENEZ, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Ramon y Cajal, Madrid, Spain

Andréa PENALOZA, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Clinique Unisersitaire Saint Luc, Brussels, Belgium

Guy MEYER, MD.PhD

Role: STUDY_CHAIR

APHP Hôpital Européen Georges Pompidou, Paris, France

EriK KLOK, MD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center Leiden, the Netherlands

Olivier HUGLI

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudois

Locations

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Hôpital Erasme

Brussels, , Belgium

Hôpital Saint-Pierre

Brussels, , Belgium

CHU de Liège

Liège, , Belgium

Hôpital de Namur

Namur, , Belgium

Angers University Hospital

Angers, , France

Hia Brest

Brest, , France

CHU Brest

Brest, , France

CHU Clermont-Ferrand

Clermont-Ferrand, , France

APHP Louis Mourier

Colombes, , France

CHU Dijon

Dijon, , France

CHU Grenoble

Grenoble, , France

Thibault Schotté

Le Mans, , France

CHU de Montpellier

Montpellier, , France

APHP Cochin

Paris, , France

APHP Hôpital Européen Georges Pompidou

Paris, , France

APHP Lariboisière

Paris, , France

CHU de Rouen

Rouen, , France

CHU Saint Etienne

Saint-Etienne, , France

CH Toulon

Toulon, , France

CHU Toulouse

Toulouse, , France

Red Cross Hospital

Beverwijk, , Netherlands

TERGOOI

Hilversum, , Netherlands

Leiden University Medical Center Leiden,

Leiden, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

Ramon y Cajal Hospital

Madrid, , Spain

Hôpital de Genève

Geneva, , Switzerland

Hôpital de Lausanne

Lausanne, , Switzerland

Countries

Belgium; France; Netherlands; Spain; Switzerland

References

Piran S, Le Gal G, Wells PS, Gandara E, Righini M, Rodger MA, Carrier M. Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis. Thromb Res. 2013 Nov;132(5):515-9. doi: 10.1016/j.thromres.2013.08.012. Epub 2013 Aug 28.

Reference Type: BACKGROUND

PMID: 24035045 (View on PubMed)

Zondag W, Kooiman J, Klok FA, Dekkers OM, Huisman MV. Outpatient versus inpatient treatment in patients with pulmonary embolism: a meta-analysis. Eur Respir J. 2013 Jul;42(1):134-44. doi: 10.1183/09031936.00093712. Epub 2012 Oct 25.

Reference Type: BACKGROUND

PMID: 23100493 (View on PubMed)

Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk Noordegraaf A, Zamorano JL, Zompatori M; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014 Nov 14;35(43):3033-69, 3069a-3069k. doi: 10.1093/eurheartj/ehu283. Epub 2014 Aug 29. No abstract available.

Reference Type: BACKGROUND

PMID: 25173341 (View on PubMed)

Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M, Renaud B, Verhamme P, Stone RA, Legall C, Sanchez O, Pugh NA, N'gako A, Cornuz J, Hugli O, Beer HJ, Perrier A, Fine MJ, Yealy DM. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011 Jul 2;378(9785):41-8. doi: 10.1016/S0140-6736(11)60824-6. Epub 2011 Jun 22.

Reference Type: BACKGROUND

PMID: 21703676 (View on PubMed)

Zondag W, Mos IC, Creemers-Schild D, Hoogerbrugge AD, Dekkers OM, Dolsma J, Eijsvogel M, Faber LM, Hofstee HM, Hovens MM, Jonkers GJ, van Kralingen KW, Kruip MJ, Vlasveld T, de Vreede MJ, Huisman MV; Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost. 2011 Aug;9(8):1500-7. doi: 10.1111/j.1538-7836.2011.04388.x.

Reference Type: BACKGROUND

PMID: 21645235 (View on PubMed)

Roy PM, Penaloza A, Hugli O, Klok FA, Arnoux A, Elias A, Couturaud F, Joly LM, Lopez R, Faber LM, Daoud-Elias M, Planquette B, Bokobza J, Viglino D, Schmidt J, Juchet H, Mahe I, Mulder F, Bartiaux M, Cren R, Moumneh T, Quere I, Falvo N, Montaclair K, Douillet D, Steinier C, Hendriks SV, Benhamou Y, Szwebel TA, Pernod G, Dublanchet N, Lapebie FX, Javaud N, Ghuysen A, Sebbane M, Chatellier G, Meyer G, Jimenez D, Huisman MV, Sanchez O; HOME-PE Study Group. Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial. Eur Heart J. 2021 Aug 31;42(33):3146-3157. doi: 10.1093/eurheartj/ehab373.

Reference Type: DERIVED

PMID: 34363386 (View on PubMed)

Other Identifiers

PHRC 2015-04

Identifier Type: -

Identifier Source: org_study_id