Pulmonary Embolism as a Cause of COPD Exacerbations

Study Overview
=================
Brief Summary
-----------------
The primary objective is to demonstrate the clinical benefits of an active strategy for the diagnosis and treatment of PE compared to usual care in patients with unexplained exacerbations of COPD who require hospital admission. The secondary objective is to assess the safety of an active strategy for the diagnosis and treatment of PE compared to usual care in patients with unexplained exacerbations of COPD who require hospital admission.

Official Title
-----------------
Efficacy and Safety of an Active Strategy for the Diagnosis and Treatment of Acute Pulmonary Embolism (PE) in Patients With Unexplained Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): a Randomized Clinical Trial

Conditions
-----------------
Pulmonary Embolism, Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Procedure: Diagnostic and therapeutic strategy: Highly sensitive D-dimer testing and, if positive, multidetector computed tomographic pulmonary angiography (MDCT).


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmation of COPD according to SEPAR-ALT criteria: post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.7; Hospital admission because COPD exacerbation without initial clinical suspicion of PE in the Emergency Department (according by the Emergency Department physician evaluation). Exclusion Criteria: Contraindication to multidetector computed tomographic angiography (allergy to intravenous contrast medium, or renal failure defined as a creatinine clearance less than 30 mL/min, according to the Cockcroft-Gault formula) Informed consent denied Pregnancy Life expectancy less than 3 months Anticoagulant therapy at the time of hospital admission Diagnosis of pneumothorax, or pneumonia (fever, and purulent sputum, and new infiltrate in chest X-ray) Diagnosis of lower respiratory tract infection (fever [>37.8ºC], increased sputum volume and/or increased sputum purulence). Indication of invasive mechanical ventilation at the time of hospital admission; Impossibility for follow-up.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active search for pulmonary embolism<br>All included patients will undergo D-dimer testing. A negative plasma highly sensitive D-dimer value (defined as a D-dimer level below the manufacturers assay threshold) will rule out pulmonary embolism, and no further examination will be performed. For patients with a positive D-dimer value, a multidetector computed tomographic pulmonary angiography (MDCT) will be performed. | Procedure: Diagnostic and therapeutic strategy: Highly sensitive D-dimer testing and, if positive, multidetector computed tomographic pulmonary angiography (MDCT).<br>* If MDCT is positive for pulmonary embolism, patients will receive anticoagulant treatment according to updated guidelines. If MDCT is negative for pulmonary embolism, patients will receive standard management for their exacerbation.<br>|
| No Intervention: Standard management<br>All included patients will undergo standard clinical management of their exacerbations, as deemed appropriate by the attending physician. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality, Symptomatic Venous Thromboembolism Recurrence, or Need for Readmission. | Clinical composite endpoint of all-cause mortality, or symptomatic venous thromboembolism recurrence, or need for readmission. | 90-day follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | All-cause mortality. | 90-day follow-up | 
| Symptomatic Recurrent Venous Thromboembolism | Symptomatic venous thromboembolic recurrence confirmed by objective testing. | 90-day follow-up | 
| Hospitalization | Need for readmission. | 90-day follow-up | 
| Major Bleeding | Major bleeding (defined according to previously published criteria) | 90-day follow-up | 
| Clinically Relevant Non Major Bleeding | Clinically relevant non major bleeding (defined according to previously published criteria) | 90-day follow-up | 
| Serious Adverse Events | Serious adverse events. | 90-day follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Venous thromboembolism, COPD exacerbations, Anticoagulation, Mortality