Evaluation of Clinical Surveillance Versus Rivaroxaban in Low-Risk Patients with Isolated Subsegmental Pulmonary Embolism: A Randomized, Placebo-Controlled Trial

The primary objective of this trial is to evaluate the **efficacy** and safety of clinical surveillance without anticoagulation in low-risk patients with isolated Subsegmental Pulmonary Embolism (SSPE). Specifically, it aims to compare the frequency of symptomatic, recurrent venous thromboembolism (VTE) in these patients when randomized to receive either clinical surveillance or anticoagulation. This is clinically relevant as it may inform treatment strategies for managing low-risk SSPE, potentially reducing unnecessary anticoagulation and its associated risks.

Secondary objectives include:

• Comparing the frequency of clinically significant bleeding and all-cause mortality in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation.
• Comparing health-related quality of life, functional status, and medical resource utilization in the same patient population under the two treatment strategies.

The clinical trial involves a total of **190 participants** who are being evaluated for the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with **Isolated Subsegmental Pulmonary Embolism** (SSPE). The study population includes both male and female subjects aged 18 years and older. Participants were selected based on specific criteria, including the requirement for informed consent and an objective diagnosis of symptomatic or asymptomatic isolated SSPE. The trial does not include a vulnerable population, and there are no specific lifestyle considerations such as diet or physical activity mentioned. The selection process ensures that participants are affiliated with the general health insurance regime, applicable only for study sites in France. The trial aims to compare the frequency of symptomatic, recurrent venous thromboembolism in low-risk patients with isolated SSPE who are randomized to receive either clinical surveillance or anticoagulation.

The clinical trial is designed to evaluate the efficacy and safety of **clinical surveillance** without anticoagulation in low-risk patients with **isolated subsegmental pulmonary embolism** (SSPE). This is a multicenter, randomized, placebo-controlled, non-inferiority trial. The trial will compare the frequency of symptomatic, recurrent venous thromboembolism (VTE) in patients randomized to receive either clinical surveillance or anticoagulation. The trial is expected to run from July 2021 to May 2026, with a total duration of 90 days for each participant's involvement.

Participants will be randomly assigned to receive either **Rivaroxaban Bayer** or a placebo. The maximum daily dose for Rivaroxaban is 30 mg, administered orally in the form of film-coated tablets, with a maximum treatment period of 21 days. The placebo will be administered similarly, with a maximum treatment period of 90 days. The primary endpoint is the proportion of recurrent, clinically symptomatic, objectively confirmed VTE within 90 days of randomization. Secondary endpoints include the proportion of clinically significant bleeding and all-cause mortality, as well as health-related quality of life, functional status, and medical resource utilization.

The sequence of study visits includes an initial screening visit to confirm eligibility, followed by randomization. Participants will undergo follow-up visits at regular intervals to monitor safety and efficacy outcomes. The end-of-study visit will occur at the conclusion of the 90-day period. Participants are required to provide informed consent, be at least 18 years of age, and have an objective diagnosis of symptomatic or asymptomatic isolated SSPE. Conditions that may lead to early termination from the study include withdrawal of consent or the occurrence of adverse events that compromise participant safety.

The clinical trial involves the administration of **Rivaroxaban Bayer**, a film-coated tablet containing the active substance **rivaroxaban**. This medication is produced by Bayer AG and is administered orally. The trial includes two dosing regimens for Rivaroxaban Bayer. The first regimen involves a maximum daily dose of 30 mg, with a total maximum dose of 630 mg over a treatment period of 21 days. The second regimen allows for a maximum daily dose of 20 mg, with a total maximum dose of 1380 mg over a treatment period of 69 days. Both regimens are designed to evaluate the efficacy and safety of the medication in the context of the trial's objectives.

The trial also includes a **placebo** for BAY 597939, which is administered orally. The placebo is used as a comparator to assess the effects of Rivaroxaban Bayer. The placebo is administered with a maximum daily dose of 30 mg, and the total maximum dose is 30 mg over a treatment period of 90 days. The use of a placebo is critical in maintaining the integrity of the trial by providing a baseline for comparison against the active treatment.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the proportion of recurrent, clinically symptomatic, objectively confirmed **venous thromboembolism (VTE)** within 90 days of randomization. This includes recurrent fatal or nonfatal pulmonary embolism (PE) or lower limb deep vein thrombosis (DVT). The secondary endpoints include the proportion of clinically significant bleeding and all-cause mortality at 90 days of randomization. Additionally, ancillary outcomes such as health-related quality of life, functional status, and medical resource utilization will be evaluated at the same timepoint.

The trial will compare the efficacy of clinical surveillance without anticoagulation against anticoagulation in low-risk patients with isolated subsegmental pulmonary embolism (SSPE). The efficacy parameters will be measured and collected at 90 days post-randomization. The analysis will focus on the frequency of symptomatic, recurrent VTE in the patient population. The trial is designed as a multicenter, randomized, placebo-controlled, non-inferiority study to ensure robust and reliable results.