PEACE Trial: Withholding vs Initiating Anticoagulation (edoxaban‑based combination therapy) in Cancer Patients with Incidental Subsegmental Pulmonary Embolism

The primary objective is to compare the clinical outcomes of withholding versus initiating anticoagulant therapy in patients with cancer who have an incidental subsegmental pulmonary embolism, assessing overall mortality, major bleeding incidence, recurrent thrombosis rates, continuation of cancer treatment, and patient‑reported quality of life to determine both therapeutic efficacy and safety.

The study population comprised adult patients (≥ 18 years) with active cancer who were incidentally found to have up to three subsegmental pulmonary emboli on routine imaging; both female and male individuals were eligible. Key inclusion requirements included the ability to provide informed consent, access to a smartphone, and a planned routine follow‑up CT scan within 3–4 months. No specific lifestyle restrictions or requirements regarding diet, physical activity, or other habits were detailed. The sponsor did not provide information on the total number of participants or additional selection details.

The study is a prospective, randomized, controlled trial comparing observation with immediate anticoagulant therapy in adult cancer patients who present with incidental subsegmental pulmonary embolism. After an initial screening visit to confirm eligibility, participants are randomized to either a withholding‑anticoagulant arm or an initiation‑anticoagulant arm in which one of the approved oral or subcutaneous agents (e.g., enoxaparin, dalteparin, tinzaparin, edoxaban, apixaban, rivaroxaban) is administered according to standard dosing. Follow‑up visits occur at 1 month, 3 months, and 6 months after randomization, with additional safety assessments as needed; a final end‑of‑study visit is performed at approximately 12 months to collect outcome data. The primary efficacy analysis utilizes a WIN ratio of a hierarchical composite endpoint that includes all‑cause mortality, imaging‑confirmed pulmonary embolism, major bleeding and clinically relevant non‑major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary endpoints assess overall bleeding, recurrent venous thromboembolism, radiologic changes in thrombosis, cancer‑treatment interruption, and quality‑of‑life measures. Participant involvement spans roughly 12 months, with the possibility of early discontinuation for reasons such as protocol‑defined adverse events, withdrawal of consent, loss to follow‑up, or death.

Edoxaban tosylate monohydrate is supplied in oral tablet form (pharmaceutical code PHF00082MIG) at a fixed dose of 60 mg per tablet. The medication is administered orally once daily throughout the treatment period. Dosing compliance is monitored by tablet count at each scheduled visit.

Apixaban is provided as an oral tablet (pharmaceutical code PHF00099MIG) containing 20 mg of active substance. The drug is taken orally once daily. Compliance assessment includes patient‑reported dosing diaries and pill counts.

Rivaroxaban tablets (pharmaceutical code PHF00082MIG) contain 30 mg of active ingredient together with lactose monohydrate as an excipient. The oral formulation is administered once daily. Adherence is evaluated by counting returned tablets and reviewing dosing logs.

Enoxaparin sodium is formulated for subcutaneous injection (pharmaceutical code PHF00231MIG) at a dose of 2 mg per kilogram of body weight. The injection is given subcutaneously once daily. Injection records and nursing administration logs are used to verify compliance.

Dalteparin sodium is supplied in a subcutaneous injectable form (pharmaceutical code PHF00231MIG) at a dose of 18 000 IU per kilogram. The medication is administered subcutaneously once daily. Compliance monitoring includes documentation of each injection in the study case report form.

Tinzaparin sodium is provided as a subcutaneous injection (pharmaceutical code PHF00231MIG) at a dose of 175 IU per kilogram. The dose is given subcutaneously once daily. Injection administration is recorded by study staff to ensure adherence.

The comparator arm of the trial involves observation without the administration of an anticoagulant, allowing assessment of outcomes in patients who withhold anticoagulant therapy versus those who receive the study medications.

Efficacy will be evaluated primarily by calculating the WIN ratio of a composite hierarchical endpoint assessed over the follow‑up period. The composite includes (1) all‑cause mortality, (2) clinically confirmed pulmonary embolism verified by imaging, (3) major bleeding defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria, and (4) clinically relevant non‑major bleeding also defined by ISTH.

Secondary efficacy assessments comprise the following parameters: clinically relevant bleeding (the sum of major bleeding and CRNMB per ISTH), occurrence of venous thromboembolism other than pulmonary embolism confirmed by imaging, radiologic evaluation of thrombosis progression, stability, or resolution by two independent radiologists, discontinuation of cancer therapy attributable to pulmonary embolism or its treatment, and health‑related quality of life measured with the EuroQol 5‑Dimension 5‑Level (EQ-5D-5L), the pulmonary embolism‑specific quality of life questionnaire (PEmb‑QoL), and the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ‑C30).

All imaging assessments will be performed using standard diagnostic modalities, and bleeding events will be classified according to ISTH definitions. Quality‑of‑life instruments are administered at predefined study visits according to the trial protocol, and data are analyzed using appropriate statistical methods for hierarchical composite outcomes and questionnaire scoring.