Pulmonary Embolism as a Cause of COPD Exacerbations

NCT02238639 | Completed Results DMC

• 1 other identifier: SLICE 1
• Study Type: interventional
• Target: 746
• Locations: 1 country
• Sites: 19

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.

Conditions

Pulmonary Embolism; Chronic Obstructive Pulmonary Disease

Keywords

Venous thromboembolism; COPD exacerbations; Anticoagulation; Mortality

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• All-cause Mortality

  90-day follow-up

• Symptomatic Recurrent Venous Thromboembolism

  90-day follow-up

• Hospitalization

  90-day follow-up

• Major Bleeding

  90-day follow-up

• Clinically Relevant Non Major Bleeding

  90-day follow-up

Study Arms (2)

Active search for pulmonary embolism

EXPERIMENTAL

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).

Standard management

NO INTERVENTION

All included patients will undergo standard clinical management of their exacerbations, as deemed appropriate by the attending physician.

Interventions

Diagnostic and therapeutic strategy: Highly sensitive D-dimer testing and, if positive, multidetector computed tomographic pulmonary angiography (MDCT). PROCEDURE

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.

Active search for pulmonary embolism

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ministry of Health, Spain: lead
• American College of Chest Physicians: collaborator
• Sociedad Española de Neumología y Cirugía Torácica: collaborator

Study Sites (19)

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital La Coruña

A Coruña, Spain

Location

Hospital Galdakao

Barakaldo, Spain

Location

Clinica Nostra Senyora del Remei

Barcelona, Spain

Location

Hospital Capio Sagrat Cor

Barcelona, Spain

Location

Hospital Cruces

Bilbao, Spain

Location

Hospital San Pedro

Logroño, Spain

Location

Hospital Ramon y Cajal, IRYCIS, Alcala de Henares University

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Alcorcon

Madrid, Spain

Location

Hospital Doce de Octubre

Madrid, Spain

Location

Hospital Gregorio Marañon

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Complejo Hospitalario Pontevedra

Pontevedra, Spain

Location

Hospital Marques de Valdecilla

Santander, Spain

Location

Policlinico La Rosaleda

Santiago de Compostela, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Hospital Txagorritxu

Vitoria-Gasteiz, Spain

Location

Hospital Lozano Blesa

Zaragoza, Spain

Location

Related Publications (15)

• Peces-Barba G, Barbera JA, Agusti A, Casanova C, Casas A, Izquierdo JL, Jardim J, Lopez Varela V, Monso E, Montemayor T, Viejo JL. [Diagnosis and management of chronic obstructive pulmonary disease: joint guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and the Latin American Thoracic Society (ALAT)]. Arch Bronconeumol. 2008 May;44(5):271-81. No abstract available. Spanish.

  PMID: 18448019 BACKGROUND

• Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J; Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55. doi: 10.1164/rccm.200703-456SO. Epub 2007 May 16.

  PMID: 17507545 BACKGROUND

• Camargo CA Jr, Roberts J, Clark S. US emergency department visits for COPD exacerbations between 1992 and 1998. Am J Epidemiol 2001; 153: S80.

  BACKGROUND

• Poulsen SH, Noer I, Moller JE, Knudsen TE, Frandsen JL. Clinical outcome of patients with suspected pulmonary embolism. A follow-up study of 588 consecutive patients. J Intern Med. 2001 Aug;250(2):137-43. doi: 10.1046/j.1365-2796.2001.00866.x.

  PMID: 11489063 BACKGROUND

• Tillie-Leblond I, Marquette CH, Perez T, Scherpereel A, Zanetti C, Tonnel AB, Remy-Jardin M. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors. Ann Intern Med. 2006 Mar 21;144(6):390-6. doi: 10.7326/0003-4819-144-6-200603210-00005.

  PMID: 16549851 BACKGROUND

• Rizkallah J, Man SFP, Sin DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009 Mar;135(3):786-793. doi: 10.1378/chest.08-1516. Epub 2008 Sep 23.

  PMID: 18812453 BACKGROUND

• Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, Lang E, Stiell I, Kovacs G, Dreyer J, Dennie C, Cartier Y, Barnes D, Burton E, Pleasance S, Skedgel C, O'Rouke K, Wells PS. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007 Dec 19;298(23):2743-53. doi: 10.1001/jama.298.23.2743.

  PMID: 18165667 BACKGROUND

• Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-e496S. doi: 10.1378/chest.11-2301.

  PMID: 22315268 BACKGROUND

• Pozo-Rodriguez F, Lopez-Campos JL, Alvarez-Martinez CJ, Castro-Acosta A, Aguero R, Hueto J, Hernandez-Hernandez J, Barron M, Abraira V, Forte A, Sanchez Nieto JM, Lopez-Gabaldon E, Cosio BG, Agusti A; AUDIPOC Study Group. Clinical audit of COPD patients requiring hospital admissions in Spain: AUDIPOC study. PLoS One. 2012;7(7):e42156. doi: 10.1371/journal.pone.0042156. Epub 2012 Jul 31.

  PMID: 22911875 BACKGROUND

• Najarro M, Briceno W, Rodriguez C, Muriel A, Gonzalez S, Castillo A, Jara I, Rali P, Toma C, Bikdeli B, Jimenez D. Shock score for prediction of clinical outcomes among stable patients with acute symptomatic pulmonary embolism. Thromb Res. 2024 Jan;233:18-24. doi: 10.1016/j.thromres.2023.11.011. Epub 2023 Nov 19.

  PMID: 37988846 DERIVED

• Rodriguez C, Muriel A, Carrasco L, Gonzalez S, Briceno W, Duran D, Retegui A, Yusen RD, Bikdeli B, Jimenez D. National Early Warning Score-2 for Identification of Patients with Intermediate-High-Risk Pulmonary Embolism. Semin Thromb Hemost. 2023 Oct;49(7):716-724. doi: 10.1055/s-0043-1769938. Epub 2023 Jun 16.

  PMID: 37327883 DERIVED

• Mirambeaux R, Rodriguez C, Muriel A, Gonzalez S, Briceno W, Duran D, Retegui A, Otero R, Bikdeli B, Jimenez D. Comparison of various prognostic scores for identification of patients with intermediate-high risk pulmonary embolism. Thromb Res. 2023 Mar;223:61-68. doi: 10.1016/j.thromres.2023.01.019. Epub 2023 Jan 23.

  PMID: 36708691 DERIVED

• Rodriguez C, Jara-Palomares L, Tabernero E, Tenes A, Gonzalez S, Briceno W, Lobo JL, Morillo R, Bikdeli B, Jimenez D. Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial. Thromb J. 2022 Mar 3;20(1):10. doi: 10.1186/s12959-022-00368-0.

  PMID: 35241119 DERIVED

• Jimenez D, Agusti A, Tabernero E, Jara-Palomares L, Hernando A, Ruiz-Artacho P, Perez-Penate G, Rivas-Guerrero A, Rodriguez-Nieto MJ, Ballaz A, Aguero R, Jimenez S, Calle-Rubio M, Lopez-Reyes R, Marcos-Rodriguez P, Barrios D, Rodriguez C, Muriel A, Bertoletti L, Couturaud F, Huisman M, Lobo JL, Yusen RD, Bikdeli B, Monreal M, Otero R; SLICE Trial Group. Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial. JAMA. 2021 Oct 5;326(13):1277-1285. doi: 10.1001/jama.2021.14846.

  PMID: 34609451 DERIVED

• Jimenez D, Agusti A, Monreal M, Otero R, Huisman MV, Lobo JL, Quezada A, Jara-Palomares L, Hernando A, Tabernero E, Marcos P, Ruiz-Artacho P, Ballaz A, Bertoletti L, Couturaud F, Yusen R; SLICE investigators. The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease. Clin Cardiol. 2019 Mar;42(3):346-351. doi: 10.1002/clc.23161. Epub 2019 Feb 25.

  PMID: 30706520 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism; Pulmonary Disease, Chronic Obstructive; Venous Thromboembolism

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thromboembolism

Results Point of Contact

• Title: David Jimenez
• Organization: Hospital Ramon y Cajal

djimenez.hrc@gmail.com

+34913368133

Study Officials

• David Jimenez, MD, PhD

  IRYCIS, Alcala de Henares University

  STUDY CHAIR

• Alvar Agusti, MD, PhD

  Hospital Clinic

  STUDY CHAIR

• Manuel Monreal, MD, PhD

  Germans Trias i Pujol Hospital

  STUDY CHAIR

• Remedios Otero, MD, PhD

  Hospital Virgen del Rocio

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 12, 2014
• Study Start: October 1, 2014
• Primary Completion: October 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 1, 2022
• Results First Posted: November 7, 2022

Record last verified: 2022-11

Locations

ES (19)