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

Pulmonary Embolism Clinical Trial

— HOME-PE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02811237
• Other study ID #: PHRC 2015-04
• Status: Completed
• Phase: N/A
• Start date: January 2017
• Est. completion date: October 30, 2019

Study information

• Verified date: October 2019
• Source: University Hospital, Angers
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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,

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 information / eligibility

• Status: Completed
• Enrollment: 1975
• Est. completion date: October 30, 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Other:
• 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.
• 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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hôpital Erasme	Bruxelles
Belgium	Hôpital Saint-Pierre	Bruxelles
Belgium	CHU de Liège	Liege
Belgium	Hôpital de Namur	Namur
France	Angers University Hospital	Angers
France	CHU Brest	Brest
France	Hia 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
Netherlands	Red Cross Hospital	Beverwijk
Netherlands	TERGOOI	Hilversum
Netherlands	Leiden University Medical Center Leiden,	Leiden
Netherlands	University Medical Center Utrecht	Utrecht
Spain	Ramon y Cajal Hospital	Madrid
Switzerland	Hôpital de Genève	Geneve
Switzerland	Hôpital de Lausanne	Lausanne

Sponsors (6)

Lead Sponsor	Collaborator
University Hospital, Angers	Cliniques universitaires Saint-Luc- Université Catholique de Louvain, European Georges Pompidou Hospital, Hospital Universitario Ramon y Cajal, Leiden University Medical Center, University of Lausanne Hospitals

Countries where clinical trial is conducted

Belgium,  France,  Netherlands,  Spain,  Switzerland, 

References & Publications (5)

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. — View Citation

Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè 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. Erratum in: Eur Heart J. 2015 Oct 14;36(39):2666. Eur Heart J. 2015 Oct 14;36(39):2642. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Safety endpoints - Recurrent VTE	The rate of recurrent VTE	14 days, 30 days, 90 days
Secondary	Safety endpoints - Suspected recurrent VTE	The rate of recurrent VTE suspicion	14 days, 30 days, 90 days
Secondary	Safety endpoints - Major Bleeding	The rate of major bleeding	14 days, 30 days, 90 days
Secondary	Safety endpoints - Non major bleeding	The rate of non-major clinically relevant bleeding	14 days, 30 days, 90 days
Secondary	Safety endpoints - Death	The rate of all-cause death	14 days, 30 days, 90 days
Secondary	Safety endpoints - Serious adverse event	The rate of serious adverse event as defined in good clinical practice	14 days, 30 days, 90 days
Secondary	Applicability of management strategies	The rate of patients actually managed as outpatients among number of patientpatients eligible for outpatient management	1 day
Secondary	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
Secondary	Patient satisfaction with care	A specific questionnaire will be used at 30 days following inclusion: - Anti-Clot Treatment - Specific Questionnaire (ACTS)	30 days
Secondary	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