Safety and Efficiency of the YEARS Algorithm Versus Computed Tomography Pulmonary Angiography Alone for Suspected Pulmonary Embolism in Patients With Malignancy (HYDRA)

Safety and Efficiency of the YEARS Algorithm Versus Computed Tomography Pulmonary Angiography Alone for Suspected Pulmonary Embolism in Patients With Malignancy : HYDRA Study

The aim of this study is to prospectively validate the safety and efficiency of management according to the YEARS algorithm to safely rule out clinically suspected PE in patients with active malignancy to be compared with 'standard' management by computed tomography pulmonary angiography (CTPA) alone in a randomized study.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Cancer; Embolism; Embolism and Thrombosis; Pulmonary Embolism; Diagnosis
• Intervention / Treatment: Procedure: CTPA; Procedure: YEARS algorithm

Detailed Description

Recently, the YEARS-algorithm was demonstrated to be a safe and efficient diagnostic strategy for patients with clinically suspected pulmonary embolism (PE). It is recognized that diagnostic algorithms for pulmonary embolism (PE) may not be as effective and safe in patients with malignancy, due to the low specificity of D-dimer test in that setting. A diagnostic algorithm that could safely rule out PE in patients with malignancy without performing computed tomography pulmonary angiography (CTPA) could nonetheless improve patient care.

• Study Type: Interventional
• Enrollment (Actual): 698
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • Antwerpen University Hospital (UZA)
  • Brussels, Belgium
    • Cliniques Universitaires Saint-Luc (CUSL)
  • Liège, Belgium
    • Centre Hospitalier Universitaire de Liège (CHU Liège)
• France
  • Brest, France, 29609
    • CHU Brest
  • Clermont-Ferrand, France, 63003
    • CHU Clermont-Ferrand
  • Colombes, France, 92700
    • Hôpital Louis Mourier - APHP
  • Paris, France, 75015
    • HEGP
  • Saint-Etienne, France, 42055
    • Chu Saint-Etienne
• Italy
  • Milan, Italy
    • Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda
  • Roma, Italy
    • Fondazione Policlinico Universitario A. Gemelli IRCCS
• Netherlands
  • 's-Hertogenbosch, Netherlands
    • Jeroen Bosch ziekenhuis
  • Almere Stad, Netherlands
    • Flevoziekenhuis
  • Amsterdam, Netherlands
    • Amsterdam UMC
  • Arnhem, Netherlands
    • Rijnstate Ziekenhuis
  • Breda, Netherlands
    • Amphia ziekenhuis
  • Delft, Netherlands
    • Reinier de Graaf Gasthuis
  • Gouda, Netherlands
    • Groene Hart Ziekenhuis
  • Hilversum, Netherlands
    • Tergooi Mc
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Nijmegen, Netherlands
    • Radboud UMC
  • Rotterdam, Netherlands
    • Maasstad Ziekenhuis
  • The Hague, Netherlands
    • Haaglanden Medisch Centrum
  • Uden, Netherlands
    • Bernhoven Ziekenhuis
  • Utrecht, Netherlands
    • Diakonessenhuis
• Spain
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
• Switzerland
  • Bern, Switzerland
    • The Inselspital Bern
  • Geneva, Switzerland
    • Hopitaux Universitaires de Geneve (HUG)
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois (CHUV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Clinically suspected PE as judged by the treating clinician
• Any type of active malignancy (other than basal-cell or squamous-cell carcinoma of the skin), defined as diagnosis within six months before the study inclusion (as confirmed histologically or high suspicion as judged by the clinician), receiving treatment for malignancy at time of inclusion or during 6 months prior to randomization, including recurrent or local metastatic malignancy
• Outpatients and hospitalized patients
• Age ≥ 18 years
• Signed and dated informed consent, available for start of the trial procedure

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Medical or psychological condition that would not permit completion of the study or signing of informed consent, including life expectancy less than 3 months, or unwillingness to sign informed consent
• Treatment with full-dose therapeutically dosed anticoagulation that was initiated 24 hours or more prior to eligibility assessment

• Contraindication to CTPA

  • contrast allergy

Hemodynamic instability at presentation (as a consequence of concurrent acute PE or otherwise), indicated by at least one of the following:

• systolic blood pressure (SBP) < 100 mm Hg, or heart rate >120 beats per minute or SBP drop by > 40 mm Hg, for > 15 min
• need for catecholamines to maintain adequate organ perfusion and a systolic blood pressure of > 100 mmHg
• Need for cardiopulmonary resuscitation
• Inability to follow-up
• Life expectancy less than 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YEARS algorithm; Patients randomized to this arm will be evaluated according to the YEARS algorithm.	Procedure: YEARS algorithm; Patients randomized to the YEARS algorithm will be evaluated according to the YEARS algorithm consisting of three items of the original Wells rule (clinical signs of DVT, haemoptysis and 'PE most likely diagnosis') and a D-dimer test. In patients without any of the three items and a D-dimer level <1.0 μg/mL (<1000ng/mL), and in patients with ≥1 items and a D-dimer level <0.5 μg/mL (<500 ng/mL) a PE is excluded without CTPA. In the other patients a standard contrast enhanced CTPA will be performed according to local practice. PE is defined as at least one filling defect in the pulmonary artery tree on CTPA.
Active Comparator: CTPA as single test; Patients randomized to this arm will undergo a contrast enhanced CTPA.	Procedure: CTPA; Patients randomized to the CTPA management group will undergo a contrast enhanced CTPA to rule out PE according to standard local practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent PE	Recurrent PE will be observed	3 months
Deep vein thrombosis (DVT)	Number of DVT will be observed	3 months
Mortality	The mortality will be observed Adjudicated according to ISTH definition in which both PE-related death as well as unexplained death will count towards primary outcome	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CTPA	Number of performed CTPA will be observed in the YEARS-group at baseline	3 months

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Radboud University Medical Center; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; University Hospital, Geneva; Centre Hospitalier Universitaire Vaudois; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; University Hospital, Brest; University Hospital, Antwerp; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Hospital Universitario Ramon y Cajal; Maasstad Hospital; Diakonessenhuis, Utrecht; Groene Hart Ziekenhuis; Reinier de Graaf Groep; Bernhoven Hospital; Medisch Spectrum Twente; Hôpital Louis Mourier; Amphia Hospital; Tergooi Hospital; Flevo Ziekenhuis, Almere; Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Menno Huisman, Pr, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): August 23, 2025
• Study Completion (Actual): August 23, 2025

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Lung Diseases; Cardiovascular Diseases; Pulmonary Embolism; Disease; Vascular Diseases; Embolism; Respiratory Tract Diseases; Embolism and Thrombosis; 4-((1,4,8,11-tetraazacyclotetradec-1-yl)methyl)benzoic acid
• Other Study ID Numbers: HYDRA (NL68754.058.19)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• IPD Sharing Access Criteria: Data access requests will be reviewed by an internal committee . Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No