1/2 Sickle Cell Disease and CardiovAscular Risk - Red cell Exchange Trial (SCD-CARRE Trial)

1/2 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: 10402364
• 负责人: Mark T Gladwin
• 金额: $ 68.06万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402364
• 关键词: Accelerometer; Accident and Emergency department; Activities of Daily Living; Acute; Adult; Adverse effects; Age; Alloimmunization; Antigens; Biological Markers; Blood; Blood capillaries; Cardiac Catheterization Procedures; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cessation of life; Childhood stroke; Chronic; Chronic Kidney Failure; Clinical; Clinical Trials; Cohort Studies; Consensus; Deceleration; Development; Diagnosis; Disease; Disease Progression; Doppler Echocardiography; Elderly; Erythrocytes; Event; Failure; Functional disorder; Genes; Healthcare; Heart Diseases; Heart Injuries; Hemoglobin; Hemoglobin SS; Hemolytic Anemia; Home; Hospitals; Infusion procedures; Injury to Kidney; Iron; Left; Measures; Meta-Analysis; Microalbuminuria; Morbidity - disease rate; Multivariate Analysis; Myocardial dysfunction; Operative Surgical Procedures; Organ; P-Selectin; Pain; Pathogenesis; Patients; Pattern; Pharmaceutical Preparations; Physiological; Plasma; Point Mutation; Polymers; Premature Mortality; Prevention; Probability; Proteinuria; Pulmonary Hypertension; Pulse Pressure; Reaction; Risk; Safety; Sickle Cell; Sickle Cell Anemia; Stroke; Sudden Death; Testing; Therapeutic Intervention; Time; Transfusion; Treatment Efficacy; Ventricular; Visit; Walking; acute chest syndrome; beta Globin; beta Thalassemia; cardiovascular risk factor; chronic pain; disorder risk; exercise capacity; functional loss; hazard; health related quality of life; hemoglobin B; high risk; improved; inhibitor; intervention effect; lung injury; lung pressure; meter; mortality; mortality risk; mutant; prevent; pro-brain natriuretic peptide (1-76); pulmonary arterial pressure; right ventricular failure; sildenafil; standard of care; therapeutic evaluation; therapeutically effective; vaso-occlusive crisis

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 Dopplerechocardiographic 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，SCD的所有主要心血管并发症 没有批准或共识疗法。患有肺动脉高压和舒张期的风险 可以通过实验室测试（NT-ProBNP）和多普勒心电图学评估心脏病。 （估计的肺动脉收缩压）。最近大约6000例SCD患者的荟萃分析 证明具有升高三尖替代射流速度（TRV）的患者是多普勒超声心动图测量值，估计肺动脉收缩压，估计了估计 在6分钟的步行测试中，比没有升高的TRV的步行测试少30.4米，而高架TRV相关 死亡率高（危险比为4.9）。在两个大型注册表中，SCD的成年患者，我们发现 大约20％的成人SCD人群的两个生物标志物具有较高的值，定义为TRV≥2.5 每秒米和NT-Probnp≥160pg/ml，该组的12个月死亡率为7.9％ 与正常TRV或NT-proBNP值的患者相比为0.5％，住院的风险比 1.6。这表明TRV和NT-Probnp的简单筛选曲线可以识别约20％的患者 SCD处于死亡和住院的最高风险。鉴于死亡率增加和早期丧失 SCD成年人中与心血管疾病相关的功能能力，测试有效很重要 此类患者的治疗干预措施。红细胞输血是通过简单或 交换输血，后者消除了患者的血液，并用输血的红细胞代替。 交换输血已被证明可有效地急性治疗几乎所有SCD并发症，包括 严重的急性胸部综合征，中风，脾或肝固隔次和多器官衰竭，也是 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进展，提高运动能力并预防间隔 血管熟悉的疼痛危机和急性增加肺部的急性胸部综合征的发作 压力并导致右心衰竭。我们建议进行临床试验以评估自动化的影响 与150名成人的护理标准相比，患者发病率和死亡率交换输血 高风险SCD患者。该试验将利用大学的现有协调中心基础设施 匹兹堡，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，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。