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

Primary Purpose

Cancer, Rivaroxaban, Venous Thromboembolism

Status

Recruiting

Phase

Phase 3

Locations

Brazil

Study Type

Interventional

Intervention

Rivaroxaban

Enoxaparin

About this trial

This is an interventional prevention trial for Cancer focused on measuring Direct oral anticoagulants, Gynecologic cancer, Low-molecular weight heparin

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

Science Valley Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rivaroxaban

Enoxaparin

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Clinically relevant bleeding

A combination of major bleeding plus clinically relevant non-major bleeding at 30 days post-operative.

Full Information

NCT ID

NCT04999176

First Posted

August 3, 2021

Last Updated

August 3, 2021

Sponsor

André Luiz Malavasi Longo de Oliveira

Collaborators

Science Valley Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT04999176

Brief Title

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

Acronym

VALERIA

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.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Recruiting

Study Start Date

October 22, 2020 (Actual)

Primary Completion Date

July 15, 2024 (Anticipated)

Study Completion Date

July 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

André Luiz Malavasi Longo de Oliveira

Collaborators

Science Valley Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer, Rivaroxaban, Venous Thromboembolism, Thromboprophylaxis

Keywords

Direct oral anticoagulants, Gynecologic cancer, Low-molecular weight heparin

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

440 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Rivaroxaban

Arm Type

Experimental

Arm Description

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

Arm Title

Enoxaparin

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rivaroxaban

Other Intervention Name(s)

Xarelto

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Enoxaparin

Other Intervention Name(s)

Clexane

Intervention Description

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.

Primary Outcome Measure Information:

Title

Venous thromboembolism and VTE related-death

Description

Time Frame

At day 30 +/- post hospital discharge

Secondary Outcome Measure Information:

Title

Clinically relevant bleeding

Description

A combination of major bleeding plus clinically relevant non-major bleeding at 30 days post-operative.

Time Frame

At day 30 +/- post hospital discharge

Other Pre-specified Outcome Measures:

Title

A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death

Description

A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death.

Time Frame

At day 30 +/- post hospital discharge

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

89 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

André Luiz Oliveira, MD

Phone

+5508005917817

drandreluiz@yahoo.com.br

First Name & Middle Initial & Last Name or Official Title & Degree

Leandro Agati, PhD

Phone

+551144688183

agati@svriglobal.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eduardo Ramacciotti, MD, PhD

Organizational Affiliation

Science Valley Research Institute

Official's Role

Study Chair

Facility Information:

Facility Name

Science Valley Research Institute

City

Santo André

State/Province

São Paulo

ZIP/Postal Code

09030370

Country

Brazil

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29848769

Citation

Ohashi Y, Ikeda M, Kunitoh H, Sasako M, Okusaka T, Mukai H, Fujiwara K, Nakamura M, Kimura T, Ibusuki K, Sakon M. Venous thromboembolism in patients with cancer: design and rationale of a multicentre, prospective registry (Cancer-VTE Registry). BMJ Open. 2018 May 30;8(5):e018910. doi: 10.1136/bmjopen-2017-018910.

Results Reference

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PubMed Identifier

27432042

Citation

Comerota AJ, Ramacciotti E. A Comprehensive Overview of Direct Oral Anticoagulants for the Management of Venous Thromboembolism. Am J Med Sci. 2016 Jul;352(1):92-106. doi: 10.1016/j.amjms.2016.03.018. Epub 2016 Apr 6.

Results Reference

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PubMed Identifier

32589230

Citation

Guntupalli SR, Brennecke A, Behbakht K, Tayebnejad A, Breed CA, Babayan LM, Cheng G, Ramzan AA, Wheeler LJ, Corr BR, Lefkowits C, Sheeder J, Matsuo K, Flink D. Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e207410. doi: 10.1001/jamanetworkopen.2020.7410.

Results Reference

background

PubMed Identifier

31381464

Citation

Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, Wong SL, Balaban EP, Flowers CR, Francis CW, Gates LE, Kakkar AK, Levine MN, Liebman HA, Tempero MA, Lyman GH, Falanga A. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020 Feb 10;38(5):496-520. doi: 10.1200/JCO.19.01461. Epub 2019 Aug 5.

Results Reference

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PubMed Identifier

30779598

Citation

Chan NC, Weitz JI. Rivaroxaban for prevention and treatment of venous thromboembolism. Future Cardiol. 2019 Mar;15(2):63-77. doi: 10.2217/fca-2018-0076. Epub 2019 Feb 19.

Results Reference

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

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