FOCUS Hip Fracture Transfusion Trial: Delirium and Other Cognitive Outcomes

描述（由申请人提供）：拟议的是一项辅助研究输血治疗试验对接受手术髋部骨折修复的心血管患者的功能结局（FOCUS），以检查200名受试者（每个随机分组100名）的血红蛋白干预对谵妄的影响。FOCUS是一项由NHLBI资助的2000名髋部骨折患者的随机临床试验，旨在验证更高的输血阈值不能改善功能恢复或降低发病率和死亡率的假设。患者随机接受足够的血液以维持血红蛋白水平bbb10 g/dL，如果血红蛋白水平低于8 g/dL或出现贫血症状时接受输血（对症策略）。这项辅助研究将扩展我们对输血阈值对谵妄的影响的理解。主要目的是确定与10 g/dL输血策略相比，症状性输血策略（8 g/dL）是否与住院期间更严重的急性谵妄症状相关。次要目的是研究输血随机化是否也影响出院后30天谵妄症状的持续，并研究住院和谵妄症状持续30天与后来功能结局的关系。这200名受试者将从16个焦点试验点招募。FOCUS研究对象为髋部骨折患者，年龄50岁以上，有心血管疾病或心血管危险因素病史，术后3天内血红蛋白水平低于10 g/dL。受试者将在随机化前、随机化后最多3天（住院）和随机化后30天评估谵妄。结果包括30天和60天的发病率、死亡率、下肢功能、日常生活工具活动和出院地点。我们的样本量预测旨在检测中等效应。采用广义估计方程对两组100例髋部骨折患者采用所有测量时间点的纵向模式进行评价。在分析中将遵循处理原则的意图。分析将通过随机分组进行，敏感性分析将检查组间重要混杂因素是否存在差异及其对分析的影响。表演地点(S)：马里兰大学巴尔的摩分校，巴尔的摩，医学博士新泽西医学和牙科大学，新不伦瑞克，新泽西州贝斯以色列女执事医疗中心，哈佛医学院，波士顿，马萨诸塞州巴尔的摩研究与教育基金会，医学博士佩里点罗伯特伍德约翰逊医院，新不伦瑞克，新泽西伦敦健康科学中心，加拿大多伦多，梅奥诊所，圣玛丽医院，罗切斯特，密歇根州桑尼布鲁克，加拿大多伦多约翰霍普金斯湾景医疗中心，巴尔的摩MD库珀大学医院，卡姆登，新泽西渥太华大学，加拿大渥太华东弗吉尼亚医学院，弗吉尼亚州诺福克哥伦比亚大学医学中心，纽约，纽约纽约长老会医院，纽约，纽约克利夫兰诊所，克利夫兰，这是一项大型临床试验（R01 HL073958）的辅助研究，该试验研究了在患有心血管疾病或心血管危险因素的患者中，不同水平的输血治疗髋部骨折手术后失血的效果。这项辅助研究探讨输血是否有助于预防谵妄的短期（随机化后）和长期（30天）变化。

DESCRIPTION (provided by applicant): Proposed is an ancillary study to the Transfusion Therapy Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) to examine the impact of the hemoglobin interventions on delirium in a sub-sample of 200 subjects (100 per randomization group). FOCUS is a randomized clinical trial of 2,000 hip fracture patients funded by the NHLBI designed to test the hypothesis that a higher blood transfusion threshold does not improve functional recovery or reduce morbidity and mortality. Patients are randomized to receive enough blood to maintain hemoglobin level >10 g/dL versus receiving transfusion if hemoglobin level is less than 8 g/dL or when symptoms of anemia develop (symptomatic strategy). This ancillary study will extend our understanding the effects of transfusion thresholds on delirium. The primary aims are to determine whether a symptomatic transfusion strategy (8 g/dL) is associated with more severe symptoms of acute delirium during hospitalization compared to a 10 g/dL transfusion strategy. Secondary aims will examine whether the transfusion randomization also affects persistence of delirium symptoms at 30 days post-discharge and will examine the association of in hospital and 30-day persistence of delirium symptoms on later functional outcomes. The 200 subjects will be recruited from 16 FOCUS sites. FOCUS subjects are hip fracture patients, ages 50+, with a history of CVD or cardiovascular risk factors, and who have a post-operative hemoglobin level less than 10 g/dL within 3 days of surgery. Subjects will be assessed for delirium pre- randomization, for up to 3 days post-randomization (in-hospital), and at 30 days post-randomization. Outcomes include 30- and 60-day morbidity, mortality, lower extremity function, instrumental activities of daily living, and discharge location. Our sample size projections seek to detect medium effects. Generalized Estimation Equations will be used to evaluate the longitudinal patterns between the two groups of 100 hip fracture patients using all measurement time points. Intention to treat principles will be followed in the analyses. Analyses will be done by randomization group, and sensitivity analyses will examine whether there are differences in important confounders between groups and their effects on the analyses. PERFORMANCE SITE(S): University of Maryland Baltimore, Baltimore, MD University of Medicine and Dentistry of New Jersey, New Brunswick, NJ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Baltimore Research & Education Foundation, Perry Point, MD Clinical Sites: Robert Wood Johnson Hospital, New Brunswick, NJ London Health Science Center, Toronto, Canada Mayo Clinic, St. Mary's Hospital, Rochester, MI Sunny Brook, Toronto, Canada Johns Hopkins Bayview Medical Center, Baltimore MD Cooper University Hospital, Camden, NJ University of Ottowa, Ottowa, Canada Eastern Virginia Medical School, Norfolk, VA Columbia University Medical Center, New York, NY New York Presbyterian Hospital, New York, NY Cleveland Clinic, Cleveland, OH Lahey Clinic Medical Center, Burlington, MA Emory University, Atlanta, GA Texas Technical, Lubbock, TX Maimondes Medical Center, Brooklyn, NY University of British Columbia, Vancouver, Canada This is an ancillary study to a large clinical trial (R01 HL073958) that looks at different levels of blood transfusion to treat blood loss after hip fracture surgery, in patients who also have cardiovascular disease or cardiovascular risk factors. This ancillary study examines whether transfusion helps prevent short-term (post- randomization) and long-term (30 day) changes in delirium.