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

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 hospitalised 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.