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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter, Open-label, Prospective, Randomized, Active-controlled Study on the Efficacy and Safety of Oral Rivaroxaban Versus Enoxaparin for Venous Thromboembolism Prophylaxis After Major Gynecological Cancer Surgery.

Conditions
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Cancer, Rivaroxaban, Venous Thromboembolism, Thromboprophylaxis

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study aims to evaluate the efficacy and safety of oral rivaroxaban 10 mg for 30 days in thromboprophylaxis after gynecological pelvic cancer surgery compared to subcutaneous enoxaparin 40 mg. 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 ISTH criteria.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br>Oral Rivaroxaban (10 mg once daily) for 30 days post-operative | Drug: Rivaroxaban<br>* Patients will be submitted to an initial screening evaluation during hospitalization. At discharge, they will be randomized and enrolled to be treated with oral rivaroxaban (10 mg once daily, for 30 days), once randomized to this group. A mandatory lower limb Doppler ultrasound will be carried out on day 30±4 as part of the primary efficacy endpoint. A final follow-up phone call visit will be performed on day 60 postoperative.<br>* Other names: Xarelto;|
| Active Comparator: Enoxaparin<br>Subcutaneous Enoxaparin (40 mg once daily) for 30 days post-operative | Drug: Enoxaparin<br>* Patients will be submitted to an initial screening evaluation during hospitalization. At discharge, they will be randomized and enrolled to be treated with subcutaneous enoxaparin (40 mg once daily, for 30 days), once randomized to this group. A mandatory lower limb Doppler ultrasound will be carried out on day 30±4 as part of the primary efficacy endpoint. A final follow-up phone call visit will be performed on day 60 postoperative.<br>* Other names: Clexane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous thromboembolism and VTE related-death | 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. | At day 30 +/- post hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically relevant bleeding | A combination of major bleeding plus clinically relevant non-major bleeding at 30 days post-operative. | At day 30 +/- post hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Direct oral anticoagulants, Gynecologic cancer, Low-molecular weight heparin