Rivaroxaban Plus Aspirin to Manage Recurrent Venous Thromboembolic Events

NCT ID: NCT05515120

Last Updated: 2022-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-03
• Study Completion Date: 2022-07-01

Brief Summary

Venous thromboembolism affects around 10 million people per year worldwide, however, despite its high incidence, there is no systematic review or randomized trial focused on the treatment of patients with recurrent deep vein thrombosis (DVT) and/or or pulmonary embolism (PE) during anticoagulant treatment. The objective was to compare the use of Rivaroxaban plus Aspirin versus Acenocoumarol in patients with recurrent venous thromboembolism treated with rivaroxaban.

Detailed Description

Venous thromboembolism has two manifestations, deep vein thrombosis (DVT) and pulmonary embolism (PE), affects around 10 million people per year worldwide, with an annual incidence of 1-2 cases per 1000 population and increases exponentially with age. [1,2,3] DVT is a multicausal disease thought to be triggered by interactions between multiple triggering factors that may be additive or synergistic, such as active cancer, antiphospholipid syndrome (APS), or other chronic inflammatory disorders. [2,4] The contribution of genetics to the risk of thromboembolism venous traditionally includes protein C, protein S, and antithrombin deficiencies, prothrombin gene mutation, and factor V Leiden. [5] The exact epidemiology in Mexico is unknown, however, the estimated prevalence of deficiencies in a population studied in Mexico City were Protein C (PC) 0.65%, Protein S (PS) 0.65%, Antithrombin (AT) 2.04% and Plasminogen ( Plg) 2.5%. [6] For the treatment of patients with DVT and/or PE, the American Society of Hematology (ASH) guideline panel suggests using direct oral anticuagulants (DOACs) over vitamin K antagonists (VKAs), [7] however the use of a DOAC instead of a VKA for patients with DVT does not impact mortality, the use of DOACs has also been related to a reduction in the risk of DVT and major bleeding, although this was not statistically significant, the greatest advantage is that the use of DOACs do not require frequent dose adjustment, monitoring of the INR, or dietary restrictions, [8 -31] in our work center we started with DOACs as the first line of treatment.

Recurrent DVT despite anticoagulation has been related to the presence of active cancer, subtherapeutic anticoagulation, use of concomitant anticancer drugs, younger age at presentation (<65 years), and PE as the initial DVT. [32-40] Insertion of an inferior vena cava (IVC) filter was previously recommended in patients with recurrent DVT while receiving anticoagulant therapy. [41] However, the risk of recurrent DVT after IVC filter insertion is as high as 32% in cancer patients and has been associated with significant morbidity and poor quality of life; [42-46] It has been suggested that increasing the dose of low molecular weight heparin (LMWH) may be an alternative to IVC filter insertion in patients with recurrent DVT, [47-49] however, to date, there is no systematic review or randomized trial focused on the treatment of patients with recurrent DVT and/or PE during anticoagulant treatment.

The aim of the current study was to compare the use of Rivaroxaban plus Aspirin versus Acenocoumarol in the prevention of thromboembolic and bleeding events in patients with recurrent venous thromboembolism treated with rivaroxaban.

Conditions

Venous Thromboembolism; Anticoagulant-induced Bleeding; Venous Thromboses; Pulmonary Embolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Rivaroxaban plus Aspirin

Drug: Rivaroxaban 15 mg Rivaroxaban 15 mg BID

Other Names:

Xarelto 15 mg Rivaroxabana 15 mg Drug: Aspirin 300 mg

Group Type: ACTIVE_COMPARATOR

Rivaroxaban 20 MG [Xarelto]

Intervention Type: DRUG

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Aspirin 300mg

Intervention Type: DRUG

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Acenocoumarol

Drug: Acenocoumarol Other Name: Vitamin K antagonist

Group Type: PLACEBO_COMPARATOR

Acenocoumarol Oral Tablet

Intervention Type: DRUG

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Interventions

Rivaroxaban 20 MG [Xarelto]

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Intervention Type: DRUG

Aspirin 300mg

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Intervention Type: DRUG

Acenocoumarol Oral Tablet

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Intervention Type: DRUG

Other Intervention Names

Xarelto 20 mg; Acetilsalicilic acid; Vitamin K antagonist

Eligibility Criteria

Inclusion Criteria

Objectively proven first episode of venous thromboembolism (upper extremity deep vein thrombosis, proximal lower extremity deep vein thrombosis, or pulmonary embolism).

Objectively documented recurrent venous thromboembolism (either new or extended upper extremity deep vein thrombosis, proximal lower extremity deep vein thrombosis or pulmonary embolism) while taking systemic anticoagulation medication (Rivaroxaban).

Exclusion Criteria

Previous hemorrhagic stroke Ischemic stroke in the last 3 months Severe renal impairment (CrCl rates < 30 ml/min) Active liver disease (any etiology) Concomitant use of any antiplatelet (aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, etc.) Increased risk of bleeding (congenital or acquired) Uncontrolled SAH Gastrointestinal hemorrhage within the past year Anemia (Hb level < 10 g/dl) or thrombocytopenia (platelet count < 100 × 109/l) Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Mexicano del Seguro Social

OTHER_GOV

Sponsor Role: lead

Responsible Party

Maximiliano Victor Manuel Correa Lara

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Instituto Mexicano Del Seguro Social

Metepec, State of Mexico, Mexico

Countries

Mexico

Other Identifiers

000001

Identifier Type: -

Identifier Source: org_study_id