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

NCT04999176 | Unknown Phase 3 DMC

• 1 other identifier: VALERIA TRIAL
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer; Rivaroxaban; Venous Thromboembolism; Thromboprophylaxis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Clinically relevant bleeding

  At day 30 +/- post hospital discharge

Other Outcomes (1)

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

  At day 30 +/- post hospital discharge

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

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

Drug: Rivaroxaban

Enoxaparin

ACTIVE COMPARATOR

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

Drug: Enoxaparin

Interventions

Rivaroxaban 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.

Also known as: Xarelto

Rivaroxaban

Enoxaparin 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.

Also known as: Clexane

Enoxaparin

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Age \< 18 years
• Refusal of informed consent
• Physician decision that involvement in the trial was not in the patient's best interest
• 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

Sponsors & Collaborators

• André Luiz Malavasi Longo de Oliveira: lead
• Science Valley Research Institute: collaborator

Study Sites (1)

Science Valley Research Institute

Santo André, São Paulo, 09030370, Brazil

RECRUITING

Related Publications (5)

• 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.

  PMID: 29848769 BACKGROUND

• 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.

  PMID: 27432042 BACKGROUND

• 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.

  PMID: 32589230 BACKGROUND

• 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.

  PMID: 31381464 BACKGROUND

• 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.

  PMID: 30779598 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Venous Thromboembolism

Interventions

Rivaroxaban; Enoxaparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Eduardo Ramacciotti, MD, PhD

  Science Valley Research Institute

  STUDY CHAIR

Central Study Contacts

André Luiz Oliveira, MD

CONTACT

+5508005917817; drandreluiz@yahoo.com.br

Leandro Agati, PhD

CONTACT

+551144688183; agati@svriglobal.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director - São Paulo State Public Women's Health Reference Center

Model Details: 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.

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 10, 2021
• Study Start: October 22, 2020
• Primary Completion: July 15, 2024
• Study Completion: July 15, 2024
• Last Updated: August 10, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)