Utility of ultrasound in the diagnostic work-up of suspected pulmonary embolism: an open-label multicentre randomized controlled trial (the PRIME study)

Background: Prevalence of pulmonary embolism (PE) in patients referred to diagnostic imaging is decreasing, indicating a need for improving patient selection. The aim of this study was to assess reduction in referral to diagnostic imaging by integrating a bespoke ultrasound protocol and describe associated failure rate and adverse events in patients with suspected PE. Methods: In a randomized open-label multicentre trial spanning June 18, 2021, through Feb 1, 2023, adult patients with suspected PE and 1) a Wells score of 0–6 and elevated age-adjusted D-dimer or 2) Wells score >6 were randomly assigned 1:1 to direct diagnostic imaging (controls) or focused lung, cardiac, and deep venous ultrasound by unblinded investigators. Ultrasound could: 1) dismiss PE if no signs of PE and low clinical suspicion or an alternate diagnosis, 2) confirm PE in case of visible venous thrombus, ≥2 subpleural infarctions, McConnell's, or D-sign, or 3) refer to diagnostic imaging if neither category was fulfilled or a patient with confirmed PE by ultrasound required admission. Primary endpoint was proportion of patients referred to diagnostic imaging. Outcome assessors were not blinded to group assignment. All included participants were included in safety analyses. The trial was registered at clinicaltrials.gov (NCT04882579). Findings: A total of 150 patients were recruited, of whom 73 were randomized to ultrasound. Among 77 controls referred to diagnostic imaging, 26 patients had PE confirmed. In the ultrasound group, 40 patients were referred to diagnostic imaging of whom 20 had PE, reducing referral for diagnostic imaging by 45.2% (95% CI: 34.3–56.6, p < 0.0001). Three further PEs were diagnosed by presence of a DVT. During 3-month follow-up, the number of patients who did not receive anticoagulation but was diagnosed with PE was two (4%; 95% CI: 1.1–13.5) and none (0%; 95% CI: 0.0–7.0) in the ultrasound and control group, respectively. Interpretation: Ultrasound substantially reduced referral to diagnostic imaging in suspected PE. Albeit with an unacceptable failure rate. Funding: University of Southern Denmark, Odense University Hospital, Master Carpenter Sophus Jacobsen and wife's foundation, Engineer K. A. Rhode and wife foundation.