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

NCT ID: NCT04999176

Last Updated: 2021-08-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

440 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-22

Study Completion Date

2024-07-15

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.

Conditions

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Cancer Rivaroxaban Venous Thromboembolism Thromboprophylaxis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Rivaroxaban

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

Group Type EXPERIMENTAL

Rivaroxaban

Intervention Type DRUG

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.

Enoxaparin

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

Group Type ACTIVE_COMPARATOR

Enoxaparin

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Xarelto Clexane

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Science Valley Research Institute

OTHER

Sponsor Role collaborator

André Luiz Malavasi Longo de Oliveira

OTHER

Sponsor Role lead

Responsible Party

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André Luiz Malavasi Longo de Oliveira

Clinical Director - São Paulo State Public Women's Health Reference Center

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Eduardo Ramacciotti, MD, PhD

Role: STUDY_CHAIR

Science Valley Research Institute

Locations

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Science Valley Research Institute

Santo André, São Paulo, Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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André Luiz Oliveira, MD

Role: CONTACT

+5508005917817

Leandro Agati, PhD

Role: CONTACT

+551144688183

References

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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.

Reference Type BACKGROUND
PMID: 29848769 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27432042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32589230 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31381464 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30779598 (View on PubMed)

Other Identifiers

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VALERIA TRIAL

Identifier Type: -

Identifier Source: org_study_id

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