A Comparison of Anticoagulant Dosing Strategies to Reduce VTE and Mortality in Cancer Outpatients: A Randomized, Pragmatic Trial
University of Vermont
Summary
Blood clots, also known as venous thromboembolism (VTE), are a common and serious complication for people with cancer. They can lead to pain, hospitalizations, delayed cancer treatment, and even death. Although national guidelines recommend using blood thinners (anticoagulants) to prevent clots in cancer patients who are at higher risk, these medications are not commonly prescribed due to concerns about bleeding and inconvenience. This study will test different ways of using a commonly prescribed blood thinner called apixaban (brand name Eliquis) to see if it can safely and effectively reduce the risk of blood clots and death in cancer patients who are at moderate risk for VTE. The study focuses on people who have a "Khorana score" of 2, which puts them at intermediate risk for developing blood clots. The study will include approximately 996 participants with solid tumors or lymphoma who are starting or recently started cancer-directed therapy. Participants will be randomly assigned to one of three groups: Group 1: Apixaban 2.5 mg twice a day (standard prophylactic dose) Group 2: Apixaban 5 mg once a day (an alternative, more convenient dose) Group 3: No anticoagulant (standard care) Participants will take the assigned treatment (if applicable) for 6 months. Researchers will monitor whether participants develop blood clots, experience serious bleeding events, or die from any cause during the study period. By comparing these three groups, the researchers hope to learn whether a once-daily dose of apixaban can work as well as the standard twice-daily dose, and whether either dosing strategy is better than no anticoagulation at all. If successful, the study may help increase the safe use of VTE prevention in cancer patients and improve overall outcomes, especially in patients at intermediate risk. This is a pragmatic trial, meaning it is designed to fit into real-world clinical practice with minimal extra procedures. The study drug is not provided by the sponsor and will be prescribed and filled through usual care channels. Participants and their doctors will decide whether to continue the medication after the study ends.
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Age ≥ 18 years * Diagnosed with an active solid tumor or lymphoma * Starting a new systemic cancer treatment or changing cancer treatment * Khorana Risk Score of 2 (calculated based on lab and clinical data at treatment initiation) * Not currently receiving therapeutic anticoagulation * Able to provide informed consent Exclusion Criteria: * Active bleeding or high risk of bleeding (e.g., recent major surgery, CNS tumors with hemorrhagic risk) * Known contraindication to apixaban (e.g., allergy, severe liver disease, dual strong CYP3A4 and P-gp inhibitors) * Current the…
Interventions
- DrugApixaban 2.5 mg twice daily
Apixaban, a direct oral anticoagulant (DOAC), will be administered at a prophylactic dose of 2.5 mg by mouth twice daily for 6 months. This dose is guideline-recommended for VTE prevention in high-risk ambulatory cancer patients. Participants will continue their cancer-directed therapy during this time. No study-mandated visits or labs are required beyond standard care.
- DrugApixaban 5 mg once daily
Apixaban will be administered at 5 mg by mouth once daily for 6 months. This alternative prophylactic schedule is being studied to assess its effectiveness and adherence in patients with a Khorana Risk Score of 2. Participants will continue their usual cancer treatment. This arm evaluates a simplified dosing strategy in a real-world, pragmatic design.
- DrugNo anticoagulation
Participants randomized to this arm will not receive apixaban or any other anticoagulant for VTE prevention. This reflects current standard care for many cancer outpatients with moderate risk (Khorana Score = 2). Outcomes will be monitored through routine care and medical record abstraction.
Location
- University of Vermont Medical CenterBurlington, Vermont