Safety Study of Outpatient Treatment for Pulmonary Embolism

NCT ID: NCT00425542

Last Updated: 2010-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 343 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2010-06-30

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.

Conditions

Pulmonary Embolism

Study Design

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

Study Groups

Outpatient treatment

Group Type: EXPERIMENTAL

Outpatient care (vs traditional inpatient care)

Intervention Type: OTHER

Patients randomized to the outpatient arm are discharged from the emergency department within 24 hours after randomization. Patients randomized to the inpatient arm are admitted to the hospital and are discharged based on the decision of the managing physician at the hospital.

Inpatient care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Outpatient care (vs traditional inpatient care)

Patients randomized to the outpatient arm are discharged from the emergency department within 24 hours after randomization. Patients randomized to the inpatient arm are admitted to the hospital and are discharged based on the decision of the managing physician at the hospital.

Intervention Type: OTHER

Other Intervention Names

Ambulatory 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

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

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Lausanne Hospitals

OTHER

Sponsor Role: lead

Responsible Party

University of Lausanne

Principal Investigators

Drahomir Aujesky, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Lausanne, Switzerland

Donald M Yealy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Northwestern Memorial Hospital

Chicago, Illinois, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

University Hospital Saint-Luc, Université Catholique de Louvain

Brussels, , Belgium

University of Leuven

Leuven, , Belgium

University of Angers

Angers, , France

University of Argenteuil

Argenteuil, , France

University of Boulogne

Boulogne, , France

University Hospital of Brest

Brest, , France

University of Clermont-Ferrand

Clermont-Ferrand, , France

University of Dijon

Dijon, , France

University of Nantes

Nantes, , France

Hôpital Européen Georges Pompidou

Paris, , France

Hôpital Henri Mondor, Créteil

Paris, , France

Thiers

Thiers, , France

Kantonsspital Baden

Baden, , Switzerland

University of Geneva

Geneva, , Switzerland

University Hospital of Lausanne

Lausanne, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Countries

United States; Belgium; France; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 16020800 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16207738 (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: DERIVED

PMID: 21703676 (View on PubMed)

Other Identifiers

1R01HL085565-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

3200B0-112165

Identifier Type: -

Identifier Source: org_study_id

NCT00974207

Identifier Type: -

Identifier Source: nct_alias