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）

基本信息

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
项目类别：
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

项目摘要

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.

随着镰状细胞病 (SCD) 患者活到成年，持续溶血性贫血的慢性影响随着心肺器官的逐渐发育，偶发性血管闭塞事件会造成损害这最终导致肺动脉高压、左心室舒张性心脏功能障碍。疾病、心律失常、慢性肾病和猝死、所有主要心血管并发症尚无批准或共识疗法的 SCD 患有肺动脉高压和的风险。舒张性心脏病可以通过实验室测试（NT-proBNP）和多普勒进行无创评估超声心动图（估计肺动脉收缩压）。 6000 名 SCD 患者的研究表明，患者的三尖瓣反流射流速度 (TRV) 升高，是一种多普勒超声心动图测量，可估计肺动脉收缩压，步行在 6 分钟步行测试中，与未升高 TRV 的患者相比，估计减少了 30.4 米，并且升高 TRV 与高死亡率相关（风险比为 4.9）。在两个大型 SCD 成年患者登记队列中，我们发现。发现大约 20% 的成人 SCD 人群的两种生物标志物都具有较高的值，定义为 TRV ≥ 2.5 米/秒且 NT-proBNP ≥ 160 pg/mL，且 12 个月死亡率为 7.9% 该组与 TRV 或 NT-proBNP 值正常的患者中的 0.5% 相比，风险比为 1.6 住院率这表明 TRV 和 NT-proBNP 的简单筛查可以识别大约鉴于死亡率和住院率的增加，20% 的 SCD 患者死亡和住院的风险最高。在 SCD 成人中，与心血管疾病相关的功能能力的早期丧失，重要的是进行测试对此类患者进行有效的治疗干预。简单或换血，后者取出患者的血液并用输入的红血代替细胞换血已被证明对几乎所有 SCD 并发症的急性治疗有效。包括严重急性胸部综合征、中风、脾或肝隔离以及多器官衰竭，以及也长期用于预防中风和复发性急性胸部综合症。坚持认为每月换血将限制疾病进展，提高运动能力，并且预防间歇性血管闭塞性疼痛危象和急剧增加的急性胸部综合征我们建议进行一项临床试验来评估其影响。与护理标准相比，自动换血对患者发病率和死亡率的影响该试验将利用 150 名成年高危 SCD 患者进行。尽管安全且用途广泛，但匹兹堡大学将涉及 22 个经验丰富的临床中心。红细胞去除术在成年 SCD 患者中的应用，目前尚无关于其用于治疗的共识或质量疗效数据改善患有进行性终末器官功能障碍的老年高危 SCD 患者的预后。