Prediction of Anticoagulant-Related Bleeding Risk in Patients with Cancer

癌症患者抗凝相关出血风险的预测

基本信息

批准号：
10566861
负责人：
Kristen Marie Sanfilippo
金额：
$ 40.24万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-05 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10566861
关键词：
Address Anticoagulant therapy Anticoagulants Area Atrial Fibrillation Calibration Cancer Burden Cancer Patient Cessation of life Clinical Trials Data Development Diagnosis Discrimination Effectiveness Enrollment Equilibrium Fatality rate Goals Guidelines Health Personnel Hemorrhage High-Risk Cancer Histology Individual Intervention Knowledge Length Location Malignant Neoplasms Methods Modeling Morbidity - disease rate National Comprehensive Cancer Network Oral Patient Care Patients Performance Periodicals Population Positioning Attribute Prevention Prevention approach Prophylactic treatment Provider Recommendation Recurrence Research Risk Risk Factors Risk-Benefit Assessment Thrombosis Time Treatment-Related Cancer United States Venous burden of illness cancer risk clinical predictive model cohort evidence base high risk high risk population improved innovation mortality novel patient oriented personalized approach predictive modeling prevent randomized trial risk prediction model success time use treatment center tumor venous thromboembolism

项目摘要

Project Summary Among patients with cancer, the risk of anticoagulant-related major bleeding is more than double that of patients without cancer. These bleeds have a fatality rate of 7%. Current guidelines recommend indefinite anticoagulant therapy in many patients with cancer and venous thromboembolism (VTE) with periodic assessments of bleeding risk. However, no evidence-based models exist to quantify bleeding risk in patients with cancer taking anticoagulants. In addition, recent trials have demonstrated effectiveness of direct oral anticoagulants as primary prophylaxis for prevention of initial VTE in patients with cancer. Thus, there is a strong need to balance the competing risks of VTE and anticoagulant-related bleeding in patients with cancer. While there are models that quantify bleeding risk in non-cancer populations (i.e. atrial fibrillation, non- cancer associated VTE) taking anticoagulants, they have not been validated in patients with cancer. Quantification of bleeding risk in patients with cancer and VTE would allow for an evidence-based approach to preventing and treating VTE by minimizing anticoagulant therapy in patients at high-risk of bleeding and allowing for judicial use in patients at low-risk of bleeding. The overall objective of this study is to develop a prediction model for anticoagulant-related bleeding in patients with cancer and VTE on anticoagulant therapy and to calibrate that model in cancer patients at high-risk of VTE being considered for primary thromboprophylaxis with anticoagulant therapy. We will accomplish our overall objective through the following specific aims: (1) validate eight existing bleeding prediction models in a cohort of 7489 patients with cancer and VTE receiving anticoagulant therapy, (2) refine and validate a cancer-specific prediction model to quantify risk of anticoagulant-associated bleeding in patients with cancer on anticoagulant therapy for VTE, and (3) calibrate the refined bleeding prediction model in a cohort of patients with cancer receiving primary anticoagulant thromboprophylaxis enrolled in two randomized trials (AVERT and CASSINI). These aims will be addressed with an expert research team in the areas of bleeding, VTE (especially in patients with cancer) and development and implementation of risk prediction models. This proposal is innovative as it addresses a current gap in the management of patients with cancer with or at high-risk of VTE by developing a prediction model to quantify the risk of the intervention (anticoagulant therapy) to inform and guide patient care. This research will be significant because it has the potential to decrease anticoagulant-related bleeding and thus bleeding related morbidity and mortality in patients with cancer.

项目概要在癌症患者中，抗凝相关大出血的风险是普通患者的两倍多没有癌症的患者。这些出血的死亡率为 7%。目前的指南建议无限期许多癌症和静脉血栓栓塞 (VTE) 患者定期接受抗凝治疗出血风险评估。然而，不存在基于证据的模型来量化患者的出血风险患有癌症并服用抗凝剂。此外，最近的试验证明了直接口服的有效性抗凝剂作为预防癌症患者初始 VTE 的主要预防措施。因此，有一个强烈需要平衡以下患者的 VTE 和抗凝相关出血的竞争风险癌症。虽然有一些模型可以量化非癌症人群的出血风险（即心房颤动、非癌症）癌症相关的静脉血栓栓塞（VTE））服用抗凝剂，但尚未在癌症患者中得到验证。对癌症和静脉血栓栓塞患者的出血风险进行量化将允许采用基于证据的方法来治疗通过最大限度地减少高出血风险患者的抗凝治疗来预防和治疗 VTE 允许对出血风险低的患者进行司法使用。本研究的总体目标是开发一个抗凝治疗中癌症和静脉血栓栓塞患者抗凝相关出血的预测模型并在考虑进行原发性 VTE 高风险的癌症患者中校准该模型抗凝治疗预防血栓。我们将通过以下方式实现我们的总体目标具体目标：(1) 在 7489 名癌症患者的队列中验证八种现有的出血预测模型和接受抗凝治疗的 VTE，(2) 完善和验证癌症特异性预测模型以量化接受 VTE 抗凝治疗的癌症患者出现抗凝相关出血的风险，以及 (3) 在接受初级治疗的癌症患者队列中校准精细的出血预测模型抗凝血栓预防纳入两项随机试验（AVERT 和 CASSINI）。这些目标将是与出血、静脉血栓栓塞（特别是癌症患者）和风险预测模型的开发和实施。该提案具有创新性，因为它解决了通过预测来弥补目前对患有 VTE 或高风险 VTE 的癌症患者的管理差距模型来量化干预（抗凝治疗）的风险，以告知和指导患者护理。这研究将具有重要意义，因为它有可能减少抗凝相关的出血，从而癌症患者出血相关的发病率和死亡率。