A Comparison of Anticoagulant Dosing Strategies to Reduce VTE and Mortality in Cancer Outpatients: A Randomized, Pragmatic Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 996
- 试验地点
- 1
- 主要终点
- Incidence of VTE in Participants Receiving Apixaban 2.5 mg Twice Daily vs No Anticoagulation
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 therapeutic-dose anticoagulation for VTE or atrial fibrillation
- •Platelet count < 50,000/µL
- •Creatinine clearance < 25 mL/min
- •Life expectancy < 3 months
- •Pregnant or breastfeeding
- •Inability to comply with study procedures
研究组 & 干预措施
Arm 1: Apixaban 2.5 mg Twice Daily Prophylaxis
Participants in this arm will receive apixaban 2.5 mg by mouth twice daily (BID) for 6 months. This is the guideline-supported prophylactic dose for VTE prevention in high-risk ambulatory cancer patients.
干预措施: Apixaban 2.5 mg twice daily (Drug)
Arm 2 Title: Apixaban 5 mg Once Daily Prophylaxis
Participants in this arm will receive apixaban 5 mg by mouth once daily for 6 months. This alternative dosing schedule is being tested for its potential to improve adherence and maintain VTE protection in moderately high-risk cancer outpatients.
干预措施: Apixaban 5 mg once daily (Drug)
No Anticoagulation (Control)
Participants in this arm will not receive any anticoagulant prophylaxis. This approach reflects current standard-of-care practice for many patients with a Khorana Risk Score of 2, where anticoagulation is not routinely prescribed.
干预措施: No anticoagulation (Drug)
结局指标
主要结局
Incidence of VTE in Participants Receiving Apixaban 2.5 mg Twice Daily vs No Anticoagulation
时间窗: 6 months
This outcome compares the incidence of venous thromboembolism (VTE) - including deep vein thrombosis, pulmonary embolism, and other clinically relevant thromboses - between participants receiving apixaban 2.5 mg BID and those receiving no anticoagulation prophylaxis. Events will be identified through clinical care and confirmed via chart review. Both symptomatic and incidental VTEs will be included.
Incidence of VTE in Participants Receiving Apixaban 5 mg Once Daily vs No Anticoagulation
时间窗: 6 months
This outcome compares the incidence of venous thromboembolism (VTE) between participants randomized to apixaban 5 mg once daily and those receiving no anticoagulation. VTEs may include DVT, PE, or other thromboses, whether symptomatic or incidental. Events will be confirmed through medical record review. The goal is to determine whether this simplified dosing schedule provides effective VTE prevention in cancer patients with Khorana Risk Score of 2.
次要结局
- All-Cause Mortality in Participants Receiving Apixaban 2.5 mg Twice Daily vs No Anticoagulation(6 months)
- All-Cause Mortality in Participants Receiving Apixaban 5 mg Once Daily vs No Anticoagulation(6 months)
- Incidence of Clinically Significant Bleeding Events (CTCAE Grade ≥3)(6 months)
研究者
Steven Ades
Medical Director
University of Vermont