Venous Thrombosis in Cancer Outpatients: Prevention and Role of Tissue Factor

癌症门诊患者静脉血栓形成：组织因子的预防和作用

• 批准号: 7895744
• 负责人: Charles W. Francis
• 金额: $ 66.25万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895744
• 关键词: Ambulatory Care; Anticoagulant therapy; Anticoagulants; Biological Markers; Biopsy Specimen; Blinded; Blood; Blood Clot; Blood coagulation; Blood specimen; Breathing; Cancer Patient; Cessation of life; Chemotherapy-Oncologic Procedure; Chest; Clinical; Clinical Trials; Coagulation Process; Collaborations; Comprehensive Cancer Center; Consensus; Dalteparin; Development; Dose; Effectiveness; Enrollment; Event; Fibrin fragment D; Frequencies; Guidelines; Hemorrhage; Hemostatic Agents; Hemostatic function; Hospitalization; Incidence; Interruption; Laboratories; Leg; Lung; Malignant Neoplasms; Measurement; Medical; Medical center; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Outpatients; Pain; Patients; Pharmaceutical Preparations; Plasma; Population; Postoperative Period; Prevention; Preventive; Property; Prophylactic treatment; Prospective Studies; Publishing; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Research; Risk; Risk Assessment; Role; Safety; Scanning; Screening procedure; Specimen; Stratification; Swelling; System; TFPI; Testing; Thromboembolism; Thrombophilia; Thromboplastin; Thrombosis; Travel; Ultrasonography; Universities; Veins; Venous; Venous Thrombosis; X-Ray Computed Tomography; base; cancer therapy; chemotherapy; clinically significant; cohort; cost; high risk; mortality; neoplastic cell; patient population; prospective; public health relevance; trial comparing; tumor

DESCRIPTION (provided by applicant): Venous thromboembolism (VTE) is a major problem in patients with cancer, contributing to mortality and morbidity, interfering with optimum treatment and resulting in high costs. Primary prophylaxis is the most effective management strategy for VTE and is generally recommended for high-risk hospitalized patients. However, cancer treatment and the burden of VTE is shifted increasingly to the ambulatory care setting, but little information is available regarding prophylaxis in cancer outpatients. Successful prophylaxis depends on its application in patients at highest risk, and we have recently developed, validated and published a predictive risk assessment model for VTE in a population of cancer outpatients receiving chemotherapy. In the proposed study, we will build on this model to examine the safety and efficacy of VTE prophylaxis in ambulatory cancer patients and also characterize the contribution of tissue factor to VTE. The proposal is focused on two specific aims. Aim 1 will be to conduct a prospective, randomized clinical trial comparing the safety efficacy of prophylaxis with dalteparin to no treatment in reducing VTE in high-risk ambulatory cancer patients initiating chemotherapy. Patients will be randomized to receive either dalteparin 5000U subcutaneously daily or no prophylaxis for 12 weeks. They will be followed for the development of symptomatic VTE and will undergo screening with serial ultrasonography for asymptomatic DVT and chest CT scan for asymptomatic PE. All thrombotic and bleeding events will be evaluated by blinded adjudicators. Aim 2 will be to establish the value of tissue factor (TF) as a predictive marker for VTE in cancer outpatients receiving chemotherapy. Blood and samples from patients enrolled in the clinical trial described in Aim 1 and from a cohort of concurrent low-risk patients also initiating chemotherapy will be used. We will determine if baseline TF is higher in patients at high-risk compared to those at low or intermediate risk of VTE. Further, we will determine if baseline plasma tissue factor levels are predictive of VTE in the clinical trial. We will determine if increasing TF levels during chemotherapy are predictive of the development of VTE. Finally, we will determine if elevated TF levels correlate with other markers of hemostatic activation. Public Health Relevance: Patients with cancer who are receiving chemotherapy often develop blood clots in the leg veins that cause pain and swelling and can travel to the lungs causing breathing problems or death. We will conduct a clinical trial to determine if preventive treatment with a low dose of a blood thinning drug will reduce the frequency of these clots. We will also do studies to determine if certain abnormalities in the blood clotting system can help predict this problem.

描述（由申请人提供）： 静脉血栓栓塞（VTE）是癌症患者的主要问题，导致死亡率和发病率，干扰最佳治疗并导致高成本。一级预防是VTE最有效的管理策略，通常推荐用于高危住院患者。然而，癌症治疗和静脉血栓栓塞的负担越来越多地转移到门诊护理环境，但很少有关于癌症门诊患者预防的信息。成功的预防取决于其在高风险患者中的应用，我们最近开发、验证并发表了一种在接受化疗的癌症门诊患者中进行VTE的预测风险评估模型。在拟议的研究中，我们将建立在这个模型，以检查VTE预防在门诊癌症患者的安全性和有效性，也表征了组织因子的贡献，静脉血栓栓塞。该提案侧重于两个具体目标。目的1是进行一项前瞻性随机临床试验，比较达肝素预防性治疗与未治疗在降低开始化疗的高风险非卧床癌症患者VTE方面的安全性和有效性。患者将随机接受达肝素5000 U每日皮下注射或无预防性治疗，持续12周。将对他们进行随访，以确定是否出现症状性静脉血栓栓塞，并对无症状性深静脉血栓进行系列超声检查筛查，对无症状性肺栓塞进行胸部CT扫描。所有血栓形成和出血事件将由设盲的裁定者进行评价。目的2将建立组织因子（TF）作为接受化疗的癌症门诊患者VTE的预测标志物的价值。将使用入组目标1所述临床试验的患者以及同时开始化疗的低风险患者队列的血液和样本。我们将确定基线TF在高风险患者中是否高于低风险或中等风险的VTE患者。此外，我们将确定基线血浆组织因子水平是否可以预测临床试验中的静脉血栓栓塞。我们将确定化疗期间TF水平升高是否预示着VTE的发生。最后，我们将确定TF水平升高是否与其他止血激活标志物相关。公共卫生相关性：正在接受化疗的癌症患者经常在腿部静脉中形成血栓，导致疼痛和肿胀，并可能转移到肺部，导致呼吸问题或死亡。我们将进行一项临床试验，以确定是否预防性治疗低剂量的血液稀释药物将减少这些凝块的频率。我们还将进行研究，以确定血液凝固系统的某些异常是否有助于预测这个问题。