Venous Thromboembolism Prophylaxis After Gynecological Pelvic Cancer Surgery With Rivaroxaban vs Enoxaparin

Phase 3

• Conditions: Cancer; Rivaroxaban; Thromboprophylaxis; Venous Thromboembolism
• Interventions: Drug: Rivaroxaban; Drug: Enoxaparin

• Registration Number: NCT04999176
• Lead Sponsor: André Luiz Malavasi Longo de Oliveira

Brief Summary

The Valeria trial will provide high-quality evidence regarding the efficacy and safety of oral rivaroxaban in thromboprophylaxis after gynecological pelvic cancer surgery in comparison with standard parenteral enoxaparin.

Detailed Description

Cancer-associated thrombosis is the second leading cause of mortality in cancer patients, mainly due to the most common complication, venous thromboembolism (VTE). New oral antithrombotic strategies for VTE prevention after gynecological cancer surgery might be non-inferior to parenteral low-molecular-weight heparin (LMWH) in efficacy and safety with increased adherence, comfort, and reduced costs.

This is a multicenter, open-label, prospective, randomized, active-controlled study, and non-inferiority trial. Four hundred and forty patients submitted to major gynecological cancer surgery will be randomized in a 1:1 ratio to receive either oral rivaroxaban 10 mg once daily or subcutaneous enoxaparin 40mg once daily for 30 days post-operative. The primary efficacy outcome is a combination of symptomatic VTE and VTE-related death or VTE detected by mandatory Doppler ultrasound on day 30±4 post-operative. The primary safety outcome is the incidence of major and clinically relevant non-major bleeding according to the International Society on Thrombosis and Hemostasis criteria.

Study Timeline

• Study Start: 2020-10-22
• Status Verified: 2021-08
• Study First Submitted: 2021-08-03
• Study First Submitted QC: 2021-08-03
• Last Update Submitted: 2021-08-03
• Study First Posted: 2021-08-10
• Last Update Posted: 2021-08-10
• Primary Completion: 2024-07-15
• Study Completion: 2024-07-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 440

Inclusion Criteria

• Female patients 18 years of age or older
• Have undergone major gynecological cancer surgery (staging surgery, debulking surgery, -
• Total or radical hysterectomy, unilateral or bilateral salpingo-oophorectomy, omentectomy, lymph node removal, open or laparoscopic access)
• Have signed informed consent
• Have received thromboprophylaxis with low-molecular-weight heparin, fondaparinux, or unfractionated heparin during the index hospitalization

Exclusion Criteria

• Age < 18 years
• Refusal of informed consent
• Physician decision that involvement in the trial was not in the patient's best interest
• Patients with a medical indication for anticoagulation therapy at the time of inclusion (for example, diagnosis of venous thromboembolism, atrial fibrillation, mechanical valve prosthesis)
• Patients with contraindications to anticoagulation (active bleeding, liver failure, blood dyscrasia, or prohibitive hemorrhagic risk in the investigator's assessment)
• Active cancer (excluding non-melanoma skin cancer) defined as cancer not in remission or radiotherapy requiring active chemotherapy or adjunctive therapies such as immunotherapy
• Use of strong inhibitors of cytochrome P450 (CYP) 3A4 and/or glycoprotein P (P-gp) (eg, protease inhibitors, ketoconazole, Itraconazole) and/or use of P-gp and strong inducers of CYP3A4 (how but not limiting rifampicin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine or St. John's wort)
• Creatinine clearance <30 ml / min
• Pregnancy or breastfeeding
• Known HIV infection
• Presence of one of the following uncontrolled or unstable cardiovascular diseases: stroke, ECG confirmed acute ischemia or myocardial infarction, and/or clinically significant dysrhythmia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rivaroxaban	Rivaroxaban	Oral Rivaroxaban (10 mg once daily) for 30 days post-operative
Enoxaparin	Enoxaparin	Subcutaneous Enoxaparin (40 mg once daily) for 30 days post-operative

Primary Outcome Measures

Name	Time	Method
Venous thromboembolism and VTE related-death	At day 30 +/- post hospital discharge	A composite of symptomatic objectively confirmed VTE (deep venous thrombosis, pulmonary embolism, and asymptomatic ultrasonography-confirmed, deep venous thrombosis or venous thromboembolism-related death at 30 days post-operative.

Secondary Outcome Measures

Name	Time	Method
Clinically relevant bleeding	At day 30 +/- post hospital discharge	A combination of major bleeding plus clinically relevant non-major bleeding at 30 days post-operative.

Trial Locations

Locations (1)

Science Valley Research Institute; 🇧🇷 Santo André, São Paulo, Brazil