2/2 Sickle Cell Disease and CardiovAscular Risk - Red cell Exchange Trial (SCD-CARRE Trial)

2/2 镰状细胞病和心血管风险 - 红细胞交换试验（SCD-CARRE 试验）

• 批准号: 10163253
• 负责人: Maria Mori Brooks
• 金额: $ 83.89万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10163253
• 关键词: Accelerometer; Activities of Daily Living; Acute; Address; Adult; Adverse event; Aging; Alloimmunization; Antigens; Biological Markers; Blood; Blood specimen; Car Phone; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cessation of life; Chronic; Chronic Kidney Failure; Classification; Clinical; Clinical Investigator; Clinical Trials; Clinical Trials Data Monitoring Committees; Collaborations; Communication; Communities; Consensus; Data; Data Analytics; Data Collection; Data Coordinating Center; Data Files; Data Reporting; Data Set; Databases; Development; Disease Progression; Doppler Echocardiography; Echocardiography; Effectiveness; Ensure; Erythrocyte Transfusion; Erythrocytes; Event; Exclusion Criteria; Functional disorder; Guidelines; Healthcare; Heart; Heart Diseases; Heart failure; Hemolytic Anemia; Hepatic; Home; Hospitalization; Hospitals; Human Resources; Image; Infrastructure; Infusion procedures; Intention; Intervention; Iron; Laboratories; Left; Lung; Lung diseases; Manuals; Manuscripts; Measurement; Measures; Medical center; Meta-Analysis; Methods; Monitor; Morbidity - disease rate; Multiple Organ Failure; Odds Ratio; Organ; Outcome; Pain; Patients; Phase; Population; Preparation; Prevention; Procedures; Process; Protocols documentation; Pulmonary Hypertension; Pulmonary artery structure; Quality Control; Randomized; Randomized Clinical Trials; Reaction; Recurrence; Registries; Renal function; Reporting; Research Design; Risk; Safety; Scheme; Sickle Cell Anemia; Site; Specific qualifier value; Statistical Data Interpretation; Stroke; Stroke prevention; Sudden Death; Symptoms; System; Systolic Pressure; Testing; Text Messaging; Therapeutic Intervention; Training; Transfusion; Treatment Effectiveness; Ultrasonography; Uncertainty; United States National Institutes of Health; Universities; Variant; Ventricular; Visit; Walking; Whole Blood Exchange Transfusion; Writing; acute chest syndrome; adjudication; base; cardiovascular risk factor; chronic stroke; clinical infrastructure; clinical research site; cohort; data centers; data management; data quality; data sharing; design; disorder risk; epidemiologic data; exercise capacity; experience; functional loss; hazard; health related quality of life; high risk; improved; improved outcome; inclusion criteria; meter; mortality; mortality risk; operation; pressure; prevent; primary outcome; pro-brain natriuretic peptide (1-76); research clinical testing; research study; screening; secondary outcome; standard care; standard of care; therapeutically effective

As patients with sickle cell disease (SCD) live to adulthood, the chronic impact of sustained hemolytic anemia and episodic vaso-occlusive events take their toll, with the progressive development of cardiopulmonary organ dysfunction. This culminates in the development of pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, chronic kidney disease and sudden death, all major cardiovascular complications of SCD for which there are no approved or consensus therapies. The risk of having pulmonary hypertension and diastolic heart disease can be non-invasively assessed by laboratory tests (NT-proBNP) and Doppler- echocardiography (estimated pulmonary artery systolic pressure). A recent meta-analysis of approximately 6000 patients with SCD demonstrated that patients with elevated tricuspid regurgitant jet velocity (TRV), which is an Doppler-echocardiographic measurement that estimates the pulmonary artery systolic pressure, walked an estimated 30.4 meters less in a 6 minute walk test than those without elevated TRV, and elevated TRV was associated with high mortality (hazard ratio of 4.9). In two large registry cohorts of adult patients with SCD, we found that approximately 20% of the adult SCD population have high values for both biomarkers, defined as a TRV ≥ 2.5 meters per second AND a NT-proBNP ≥ 160 pg/mL, and that the 12-month mortality rate is 7.9% in this group as compared to 0.5% in patients with normal TRV or NT-proBNP values, with a risk ratio for hospitalization of 1.6. This suggests that a simple screening profile of TRV and NT-proBNP can identify about 20% of patients with SCD at the highest risk of death and hospitalization. Given the increased mortality and early loss of functional capacity associated with cardiovascular disease in SCD adults, it is important to test effective therapeutic interventions in such patients. Red blood cell transfusions are administered by either simple or exchange transfusion, the latter removes the patients blood and replaces it with transfused red blood cells. Exchange transfusions have proven effective for acute treatment of almost all SCD complications, including severe acute chest syndrome, stroke, splenic or hepatic sequestration, and multi-organ failure, and are also used chronically for stroke prevention and recurrent acute chest syndrome. In this study we hypothesize that monthly exchange transfusion will limit disease progression, improve exercise capacity, and prevent interval episodes of vaso-occlusive painful crisis and the acute chest syndrome that acutely increases pulmonary pressures and cause right heart failure. We propose to perform a clinical trial to evaluate the effects of automated exchange blood transfusion on patient morbidity and mortality, compared to standard of care among 150 adult high risk SCD patients. The trial will leverage existing coordinating center infrastructure at the University of Pittsburgh and will involve 22 experienced clinical sites. Despite the safety and wide utilization of erythrocytapheresis in adult patients with SCD, there is no consensus or quality efficacy data on its use to improve outcomes in our aging high-risk SCD patients with progressive end-organ dysfunction.

随着镰状细胞疾病（SCD）的成年患者，持续溶血性贫血的慢性影响 随着心肺器官的逐步发展 功能障碍。这最终导致肺动脉高压的发展 疾病，心律失常，慢性肾脏疾病和猝死，所有主要心血管并发症 没有批准或共识疗法的SCD。患有肺动脉高压和 可以通过实验室测试（NT-ProBNP）和多普勒 - 可侵入性心脏病评估 超声心动图（估计的肺动脉收缩压）。最近大约的荟萃分析 6000例SCD患者表明，三尖替尖型喷气速度（TRV）的患者升高，该患者 是估计肺动脉收缩压的多普勒心电图测量值 在6分钟的步行测试中，估计比没有TRV升高的步行测试要少30.4米，而TRV的高架是 与高死亡率相关（危险比为4.9）。在两个大型注册表人群中，SCD患者，我们 发现大约20％的成人SCD人群的两个生物标志物具有很高的值，该值定义为 TRV≥2.5米/秒和NT-Probnp≥160pg/ml，12个月的死亡率为7.9％ 该组为正常TRV或NT-proBNP值的患者为0.5％，风险比率为 住院1.6。这表明TRV和NT-ProBNP的简单筛选曲线可以识别 患有最高死亡和住院风险的SCD患者中有20％。考虑到死亡率增加和 与SCD成年人心血管疾病相关的功能能力的早期丧失，测试很重要 此类患者的有效治疗干预措施。红细胞输血是通过任何一个 简单或交换输血，后者消除了患者的血液，并用输血的红血来代替。 细胞。事实证明，交换输血对几乎所有SCD并发症的急性治疗有效， 包括严重的急性胸部综合征，中风，脾或肝固隔次，多器官衰竭以及 还长期用于预防中风和复发性急性胸部综合征。在这项研究中，我们 假设每月交换输血将限制疾病的进展，提高运动能力和 防止急性增加的血管熟悉疼痛危机和急性胸部综合征的间隔发作 肺部压力并导致右心衰竭。我们建议进行临床试验以评估影响 与护理标准相比，患者发病率和死亡率的自动交换输血 在150名成人高风险患者中。该试验将利用现有的协调中心基础设施 匹兹堡大学将涉及22个经验丰富的临床场所。尽管安全和广泛利用 成人SCD患者的红细胞置换术，没有关于其使用的共识或质量效率数据 改善衰老的高风险SCD患者的结局。