DOAC – Dosing Options in AntiCoagulation Prophylaxis

Description

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in ambulatory patients with cancer, particularly within the first several months after initiating cancer-directed therapy (CDT). The Khorana Risk Score (KRS) is a validated tool used to identify cancer patients at increased risk of VTE. While patients with a KRS ≥ 2 are eligible for VTE prophylaxis under current clinical guidelines, there remains a major gap between these recommendations and clinical practice. Implementation of prophylaxis is low due to concerns about bleeding, uncertainty regarding net clinical benefit, and challenges with medication adherence-particularly with twice-daily dosing regimens.

Apixaban, a direct oral anticoagulant (DOAC), is FDA-approved and supported by NCCN and ASH guidelines for VTE prevention in high-risk ambulatory cancer patients. The AVERT trial demonstrated that apixaban 2.5 mg twice daily significantly reduced VTE events in cancer patients with a KRS ≥ 2 but increased the risk of major bleeding. However, this dosing strategy remains underutilized. The possibility of once-daily dosing with apixaban, which could improve adherence and acceptance among patients and physicians, has not been adequately studied in this population.

This single-center, phase III, open-label, pragmatic randomized clinical trial will evaluate two dosing strategies of apixaban for VTE prevention in cancer outpatients with a KRS of 2. A total of 996 participants will be randomized 1:1:1 to receive:

Arm 1: Apixaban 2.5 mg twice daily

Arm 2: Apixaban 5 mg once daily

Arm 3: No anticoagulant prophylaxis (standard care)

The primary objective is to compare the incidence of VTE across these arms over a 6-month treatment period. Secondary objectives include comparisons of all-cause mortality and rates of clinically significant bleeding events (CTCAE grade ≥ 3).

Participants must have a solid tumor or lymphoma and be initiating or recently initiated on CDT. Those with recent VTE, active anticoagulation for another indication, hematologic malignancies (e.g., acute leukemia, myeloma), or high bleeding risk are excluded.

Randomization occurs after eligibility is confirmed via chart review and informed consent is obtained. In line with a pragmatic trial design, there are no mandated study visits beyond a brief 2-month patient-reported outcomes (PRO) check-in. All other data, including VTE events, mortality, bleeding, and adherence, are captured via electronic health record abstraction and PRO questionnaires.

Drug is not provided as part of the study; apixaban will be prescribed as part of usual clinical care and filled through the participant’s pharmacy. Participants who are unable to obtain the drug due to insurance or financial barriers will still be followed in their assigned study arm per intent-to-treat principles.

The study will use a formal interim analysis following the O’Brien and Fleming approach, with stopping rules for futility and efficacy. Final analyses will compare VTE incidence and other endpoints using chi-square tests and Kaplan-Meier survival analysis, as appropriate.

This trial is designed to generate real-world evidence to inform anticoagulant prescribing practices in cancer outpatients at intermediate risk for VTE. Results may support broader, more personalized adoption of thromboprophylaxis strategies that balance effectiveness, safety, and feasibility.