FOCUS Hip Fracture Transfusion Trial: Delirium and Other Cognitive Outcomes

描述(由申请人提供)：建议对接受髋部骨折外科修复手术的心血管患者的输血疗法试验(FOCUS)进行一项辅助研究，以考察血红蛋白干预对200名受试者(每个随机组100人)的神志障碍的影响。Focus是一项由NHLBI资助的针对2000名髋部骨折患者的随机临床试验，旨在测试较高的输血门槛不会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&10g/dL，如果血红蛋白水平低于8g/dL或当出现贫血症状时接受输血(症状策略)。这项辅助研究将扩大我们对输血阈值对精神错乱的影响的理解。主要目的是确定有症状的输血策略(8g/dL)与10g/dL输血策略相比，是否与住院期间更严重的急性精神错乱症状有关。二级AIMS将检查输液随机是否也影响出院后30天精神错乱症状的持续性，并将检查住院和30天精神错乱症状持续时间与以后功能结果的关系。这200名受试者将从16个焦点地点招募。重点研究对象是髋部骨折患者，年龄50岁，有心血管病史或心血管危险因素，术后3天内血红蛋白水平低于10g/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天评估神志不清。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。我们的样本量预测试图检测中等效应。我们将使用广义估计方程来评估两组100名髋部骨折患者在所有测量时间点之间的纵向模式。分析中将遵循意向治疗原则。分析将由随机组完成，敏感性分析将检查组之间是否存在重要混杂因素的差异及其对分析的影响。演出站点(S)：马里兰大学巴尔的摩分校、新泽西医学和牙科大学、新不伦瑞克、新泽西贝丝以色列女执事医学中心、哈佛医学院、波士顿、马萨诸塞州巴尔的摩研究和教育基金会、佩里波因特、MD临床站点：罗伯特·伍德·约翰逊医院、新不伦瑞克、新泽西州伦敦健康科学中心、多伦多、加拿大梅奥诊所、圣玛丽医院、罗切斯特、MI Sunny Brook、多伦多、加拿大约翰霍普金斯贝维尤医学中心、巴尔的摩MD库珀大学医院、卡姆登、新泽西州奥托瓦大学、奥托瓦大学、加拿大东弗吉尼亚医学院、诺福克、哥伦比亚大学医学中心、纽约、加拿大约翰霍普金斯大学贝维尤医学中心、巴尔的摩MD库珀大学医院、加拿大东弗吉尼亚医学院、诺福克、哥伦比亚大学医学中心、纽约、加拿大约翰霍普金斯大学贝维尤医学中心纽约长老会医院、纽约克利夫兰诊所、俄亥俄州莱希临床医学中心、伯灵顿、马萨诸塞州埃默里大学、亚特兰大、佐治亚州得克萨斯理工学院、卢伯克、得克萨斯州梅蒙德斯医学中心、布鲁克林、不列颠哥伦比亚省纽约大学、加拿大温哥华。这是一项大型临床试验(R01 HL073958)的辅助研究，该试验旨在观察不同水平的输血以治疗髋部骨折手术后的失血，这些患者也有心血管疾病或心血管风险因素。这项辅助研究考察输血是否有助于预防神志不清的短期(随机后)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.