Clinical trial NCT04999176: Venous Thromboembolism Prophylaxis After Gynecological Pelvic Cancer Surgery With Rivaroxaban vs Enoxaparin
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cancer
Rivaroxaban
Venous Thromboembolism
Thromboprophylaxis
Keywords: Direct oral anticoagulants
Gynecologic cancer
Low-molecular weight heparin
Lead sponsor: Science Valley Research Institute
Sponsor class: OTHER
Collaborators: name: Science Valley Research Institute
First posted: 2021-08-10
Enrollment: 440
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Venous thromboembolism and VTE related-death
timeFrame: At day 30 +/- post hospital discharge
Secondary outcomes:
measure: Clinically relevant bleeding
timeFrame: At day 30 +/- post hospital discharge
Other outcomes:
measure: A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death
timeFrame: At day 30 +/- post hospital discharge
Locations:
city: Santo André
country: Brazil
facility: Science Valley Research Institute
state: São Paulo
Study officials:
affiliation: Science Valley Research Institute
name: Eduardo Ramacciotti, MD, PhD
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.