Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)

Abstract

IntroductionThe clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE.Methods and analysisSAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation.Ethics and disseminationThe local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal.Trial registration numberNCT04263038.

Management of single subsegmental pulmonary embolism: a prospective observational study at North Shore and Waitakere Hospitals, Auckland

“…A larger cohort study is limited due to the heterogeneity in data collection and management guidelines across different district health boards in New Zealand. The Clinical Surveillance vs. Anticoagulation for Low‐risk Patients with Isolated Subsegmental Pulmonary Embolism (SAFE‐SSPE) study, the first randomised control trial on the management of SSPE patients, is currently enrolling patients and will hopefully be providing some important evidence‐based guidance 11 . Second, minor bleeding or asymptomatic thrombotic events might be under‐reported either due to recollection errors or missing clinical documentation.…”

A multicentre observational study of the prevalence, management, and outcomes of subsegmental pulmonary embolism

“…This compares with 5.3% VTE recurrence, 8.1% bleeding, and 2.1% mortality for the anticoagulation treated SSPE patients in the Bariteau et al, meta-analysis [10]. However, the studies included in this meta-analysis were heterogenous with many lacking Pulmonary Embolism) [34,35] to address this important question.…”

Emergency management of incidental pulmonary embolism (IPE)

“…The management of subsegmental PE in particular remains controversial. Although there is growing evidence that not anticoagulating patients with subsegmental PE is a safe approach, the data is mainly from patients without malignancy [ 23 , 24 ]. One study of cancer patients reported that whilst symptomatic PE showed better survival with anticoagulation, anticoagulation did not result in significant survival benefit in IPE.…”