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

Sponsor

André Luiz Malavasi Longo de Oliveira (Other)

Overall Status

Recruiting

CT.gov ID

NCT04999176

Collaborator

Science Valley Research Institute (Other)

440

Enrollment

Location

Arms

44.7

Anticipated Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Rivaroxaban Venous Thromboembolism Thromboprophylaxis	Drug: Rivaroxaban Drug: Enoxaparin	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

440 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Prevention

Official Title:

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.

Actual Study Start Date :

Oct 22, 2020

Anticipated Primary Completion Date :

Jul 15, 2024

Anticipated Study Completion Date :

Jul 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban Oral Rivaroxaban (10 mg once daily) for 30 days post-operative	Drug: Rivaroxaban 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. Other Names: Xarelto
Active Comparator: Enoxaparin Subcutaneous Enoxaparin (40 mg once daily) for 30 days post-operative	Drug: Enoxaparin 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. Other Names: Clexane

Arm

Intervention/Treatment

Experimental: Rivaroxaban

Oral Rivaroxaban (10 mg once daily) for 30 days post-operative

Drug: Rivaroxaban

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.

Other Names:

Xarelto

Active Comparator: Enoxaparin

Subcutaneous Enoxaparin (40 mg once daily) for 30 days post-operative

Drug: Enoxaparin

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.

Other Names:

Clexane

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death [At day 30 +/- post hospital discharge]
A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 89 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Science Valley Research Institute	Santo André	São Paulo	Brazil	09030370

Sponsors and Collaborators

André Luiz Malavasi Longo de Oliveira
Science Valley Research Institute

Investigators

Study Chair: Eduardo Ramacciotti, MD, PhD, Science Valley Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

André Luiz Malavasi Longo de Oliveira, Clinical Director - São Paulo State Public Women's Health Reference Center, Science Valley Research Institute

ClinicalTrials.gov Identifier:

NCT04999176

Other Study ID Numbers:

VALERIA TRIAL

First Posted:

Aug 10, 2021

Last Update Posted:

Aug 10, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by André Luiz Malavasi Longo de Oliveira, Clinical Director - São Paulo State Public Women's Health Reference Center, Science Valley Research Institute

Direct oral anticoagulants

Gynecologic cancer

Low-molecular weight heparin

Additional relevant MeSH terms:

Thromboembolism

Venous Thromboembolism

Enoxaparin

Rivaroxaban

Study Results

No Results Posted as of Aug 10, 2021