A study protocol for a randomised controlled trial evaluating the safety and efficiency of the YEARS algorithm versus computed tomography pulmonary angiography only for suspected acute pulmonary embolism in patients with cancer: the Hydra Study
Abstract
Abstract Background Pulmonary embolism (PE) is frequently suspected in patients with cancer due to non-specific symptoms suggestive of PE and their inherent risk of venous thromboembolism (VTE). Commonly used clinical decision rules (CDRs) and D-dimer testing may be less reliable in this specific population. Due to the lack of guideline recommendations on the optimal diagnostic approach and the perceived futility of D-dimer in patients with cancer, clinicians often use computed tomography pulmonary angiography (CTPA) as a sole diagnostic test. This practice exposes patients to potentially unnecessary radiation and harm, and contributes to a significant burden on healthcare systems through inefficient resource allocation. The YEARS algorithm is an easy-to-use CDR that has been shown to safely exclude PE without the need for CTPA in a diverse population of patients with suspected PE. Objective To compare the safety and efficiency of the YEARS algorithm to the safety and efficiency of CTPA only in the diagnostic management of acute PE in cancer patients. Design and interventions The Hydra study ( ClinicalTrials.gov NCT04657120 ) is an investigator-initiated, multicentre, multinational open-label, randomised, non-inferiority trial with blinded adjudication of outcome events, comparing the YEARS algorithm with CTPA only in the diagnostic work-up of cancer patients with clinically suspected acute PE. Participants are randomised in a 1:1 ratio to each diagnostic strategy via a web-based system. The trial anticipates to include 1566 patients. Participants Consecutive patients with active cancer who are hospitalized or present to the emergency department, outpatient clinic, or thrombosis clinic with clinically suspected PE and who are not receiving therapeutic anticoagulation or have an indication for anticoagulation therapy other than PE. Study outcomes The primary safety outcome is the proportion of symptomatic and objectively proven fatal or non-fatal VTE (i.e., PE or deep vein thrombosis in the upper or lower extremities) or death with undetermined cause where acute PE could not be ruled out as contributing factor during three months follow-up in patients in whom PE was ruled out at initial testing. The primary efficiency outcome is the proportion of negative CTPA scans for PE, relative to the total number of CTPA scans performed at initial testing. Implication This trial will provide pivotal data on the optimal diagnostic approach for suspected acute PE in patients with cancer. Strengths and limitations of this study The Hydra study is the first prospective, randomised trial comparing the safety and efficiency of the YEARS algorithm with CTPA only for suspected acute PE in patients with active cancer. The enrolment of a large number of patients from multiple teaching and general hospitals across various clinical settings and countries enhances the generalisability of this study. The randomised design and the vulnerable study population may render the study challenging.
Authors 36
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Leiden University Medical Center
Affiliation as printed
Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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University of Bern · University Hospital of Bern
Affiliation as printed
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Affiliation as printed
Department of Internal Medicine, Reinier de Graaf Gasthuis, Delft, The Netherlands
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Università Cattolica del Sacro Cuore · Agostino Gemelli University Polyclinic · Istituti di Ricovero e Cura a Carattere Scientifico
Affiliation as printed
Percorso Trombosi, Dipartimento di Scienze dell’Invecchiamento, Ortopediche e Reumatologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences Research Institute, Pulmonary Hypertension & Thrombosis, Amsterdam, The Netherlands
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Affiliation as printed
Department of Clinical and Community Sciences, University of Milan, Millan, Italy
Emergency Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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Affiliation as printed
INSERM U1304-GETBO, INNOVTE network, Department of Pulmonology, Brest University Hospital and Brest University, Brest, France
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Università Cattolica del Sacro Cuore · Agostino Gemelli University Polyclinic · Istituti di Ricovero e Cura a Carattere Scientifico
Affiliation as printed
Percorso Trombosi, Dipartimento di Scienze dell’Invecchiamento, Ortopediche e Reumatologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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Affiliation as printed
Department of Pulmonology, Groene Hart Hospital, Gouda, The Netherlands
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University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Affiliation as printed
Department of Clinical and Community Sciences, University of Milan, Millan, Italy
Emergency Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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Affiliation as printed
Department of Medicine, Diakonessenhuis Utrecht, Utrecht, The Netherlands
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Affiliation as printed
Department of Pulmonology, Amphia Hospital, Breda, The Netherlands
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Centre Hospitalier Universitaire Vaudois · University of Lausanne
Affiliation as printed
Emergency Department, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland
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Leiden University Medical Center
Affiliation as printed
Department of Oncology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Pulmonology, Amphia Hospital, Breda, The Netherlands
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Universidad de Alcalá · Centro de Investigación Biomédica en Red de Enfermedades Respiratorias · Centro de Investigación Biomédica en Red · Instituto Ramón y Cajal de Investigación Sanitaria · Hospital Universitario Ramón y Cajal
Affiliation as printed
CIBER de Enfermedades respiratorias (CIBERES), Madrid, Spain
Department of Medicine, Universidad de Alcalá (IRYCIS), Madrid, Spain
Respiratory Department, Ramón y Cajal Hospital (IRYCIS), Madrid, Spain
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Tergooi · Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences Research Institute, Pulmonary Hypertension & Thrombosis, Amsterdam, The Netherlands
Department of Medicine, Tergooi Hospital, Hilversum, The Netherlands
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Tergooi · Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences Research Institute, Pulmonary Hypertension & Thrombosis, Amsterdam, The Netherlands
Department of Medicine, Tergooi Hospital, Hilversum, The Netherlands
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Health Sciences
Affiliation as printed
Department of Medicine, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
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Affiliation as printed
Department of Medicine, Bernhoven Hospital, Uden, The Netherlands
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Inserm · Université Paris Cité · Hôpital Louis-Mourier · Assistance Publique – Hôpitaux de Paris · Paris Cardiovascular Research Center
Affiliation as printed
Department of Medicine, Hôpital Louis-Mourier, Colombes, Assistance-Publique-Hôpitaux de Paris, Paris Cité University, INSERM Unité Mixte de Recherche U970, Paris Cardiovascular Research Center, Team “Endotheliopathy and Hemostasis Disorders”, Paris, France
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Leiden University Medical Center
Affiliation as printed
Emergency Department, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Medicine, Medisch Spectrum Twente, Enschede, The Netherlands
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Università Cattolica del Sacro Cuore · Agostino Gemelli University Polyclinic · Istituti di Ricovero e Cura a Carattere Scientifico
Affiliation as printed
Percorso Trombosi, Dipartimento di Scienze dell’Invecchiamento, Ortopediche e Reumatologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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University of Bern · University Hospital of Bern
Affiliation as printed
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Affiliation as printed
Department of Pulmonology and Thoracic Oncology, Antwerp University Hospital, Edegem, Belgium
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Affiliation as printed
Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
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Affiliation as printed
Department of Medicine, Maasstad Hospital, Rotterdam, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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Università Cattolica del Sacro Cuore · Agostino Gemelli University Polyclinic · Istituti di Ricovero e Cura a Carattere Scientifico
Affiliation as printed
Percorso Trombosi, Dipartimento di Scienze dell’Invecchiamento, Ortopediche e Reumatologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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University of Bern · University Hospital of Bern
Affiliation as printed
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Affiliation as printed
Department of Medicine, Flevo Hospital, Almere, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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