Clinical trial NCT00425542: Safety Study of Outpatient Treatment for Pulmonary Embolism
Official title: Outpatient Treatment of Low-risk Patients With Pulmonary Embolism: a Randomized-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Embolism
Keywords: Pulmonary embolism
Outpatient care
Prognosis
Lead sponsor: University of Lausanne Hospitals
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-01-23
Enrollment: 343
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The purpose of this randomized clinical trial is to determine whether outpatient treatment is as effective and safe as inpatient treatment among low-risk patients with pulmonary embolism.

Detailed description: Pulmonary embolism (PE) is a worldwide health problem, with an estimated incidence of up to 69 cases per 100,000 persons annually. In the U.S., 101,000 patients were hospitalized with a primary diagnosis of PE in 2002, resulting in direct medical costs of $720 million. There is growing evidence that outpatient treatment with low-molecular-weight heparin (LMWH) is an effective and safe option for up to 50% of patients with non-massive PE. Despite this evidence, outpatient treatment of PE is uncommon because (1) explicit criteria that identify patients who are at low-risk of adverse medical outcomes have not been available, and (2) randomized trials demonstrating the effectiveness and safety of outpatient treatment have not been performed. We developed a clinical prognostic model that accurately identifies patients with PE who are at low-risk for short-term mortality, symptomatic recurrent venous thromboembolism (VTE), and major bleeding. This model provides clinicians an easily applied, explicit risk stratification tool for patients with PE, addressing a key barrier to outpatient treatment. The broad objective of this clinical trial is to address the other major barrier to outpatient treatment of low-risk patients with non-massive PE, the effectiveness and safety of outpatient management. We will randomize low-risk patients (identified using our prognostic model) with PE from hospital emergency departments to receive outpatient or inpatient treatment with LMWH for ≥5 days, followed by oral anticoagulation. The specific aims of the project are to compare (1) the frequency of recurrent VTE, (2) the frequency of major bleeding and all-cause mortality, and (3) medical resource utilization and patient satisfaction with care among patients randomized to receive outpatient or inpatient treatment with LMWH. The primary study outcome will be the rate of symptomatic recurrent VTE at 3 months after randomization. The secondary outcomes will be the rate of major bleeding and all-cause mortality. The ancillary outcomes will be medical resource utilization and patient satisfaction with care. The hypotheses guiding this trial are that outpatient treatment with LMWH is as effective and safe as inpatient treatment with LMWH, and is also associated with reduced medical resource utilization and increase patient satisfaction with care. This study is innovative because it translates a validated prognostic model into clinical practice and represents the first direct comparison of outpatient versus inpatient treatment of low-risk patients with PE. Successful completion of this project will provide a strong scientific basis for treating low-risk patients with PE in the outpatient setting. Outpatient management of low-risk patients with PE is likely to improve quality and efficiency of care by reducing resource utilization and increasing patient satisfaction with care. Our findings will have importance to physicians, hospitals, and policy-makers who are committed to optimizing patient safety and providing high-quality, cost-effective care.

Eligibility criteria: Inclusion Criteria:

* age \>18 years
* objectively confirmed diagnosis of pulmonary embolism
* patients at low-risk (Pulmonary Embolism Severity Index score \<=85)

Exclusion Criteria:

* patients at high-risk (Pulmonary Embolism Severity Index score \>85)
* presence of hypoxemia (arterial SO2 \<90% measured by pulse oximetry or an paO2 on room air of \<60 mm Hg measured by blood gas analysis)
* systolic blood pressure of \<100 mm Hg
* chest pain necessitating parenteral opioid administration
* active bleeding or at high-risk of major bleeding (stroke during the preceding 10 days, gastrointestinal bleeding during the preceding 14 days, or platelets \<75,000 per mm3)
* renal failure (creatinine clearance of \<30 ml/minute based on the Cockcroft-Gault formula)
* body mass \>150 kg
* history of HIT or allergy to heparins
* therapeutic oral anticoagulation (INR ≥2)at the time of pulmonary embolism diagnosis
* potential barriers to treatment adherence or follow-up (alcoholism, illicit current or recent drug use, psychosis, dementia, homelessness, lack of telephone access, transportation time to nearest ED \>45 minutes)
* known pregnancy
* imprisonment
* diagnosis of pulmonary embolism \>23 hours ago
* refusal or inability to provide informed consent
* prior enrollment in the study

Primary outcomes:
measure: Recurrent, symptomatic venous thromboembolism (deep vein thrombosis or pulmonary embolism)
timeFrame: within 3 months of randomization
Secondary outcomes:
measure: Major bleeding
timeFrame: within 3 months of randomization
measure: All-cause mortality
timeFrame: within 3 months of randomization
measure: Patient satisfaction with care
timeFrame: within 2 weeks of randomization
measure: Medical resource utilization
timeFrame: within 3 months of randomization
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Brussels
country: Belgium
facility: University Hospital Saint-Luc, Université Catholique de Louvain
city: Leuven
country: Belgium
facility: University of Leuven
city: Angers
country: France
facility: University of Angers
city: Argenteuil
country: France
facility: University of Argenteuil
city: Boulogne
country: France
facility: University of Boulogne
city: Brest
country: France
facility: University Hospital of Brest
city: Clermont-Ferrand
country: France
facility: University of Clermont-Ferrand
city: Dijon
country: France
facility: University of Dijon
city: Nantes
country: France
facility: University of Nantes
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Henri Mondor, Créteil
city: Thiers
country: France
facility: Thiers
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Geneva
country: Switzerland
facility: University of Geneva
city: Lausanne
country: Switzerland
facility: University Hospital of Lausanne
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
Study officials:
affiliation: University of Lausanne, Switzerland
name: Drahomir Aujesky, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Donald M Yealy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1041-6. doi: 10.1164/rccm.200506-862OC. Epub 2005 Jul 14.
citation: Aujesky D, Roy PM, Le Manach CP, Verschuren F, Meyer G, Obrosky DS, Stone RA, Cornuz J, Fine MJ. Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J. 2006 Feb;27(4):476-81. doi: 10.1093/eurheartj/ehi588. Epub 2005 Oct 5.
citation: 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.