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）

基本信息

批准号：
10026435
负责人：
Mark T Gladwin
金额：
$ 277.58万
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/10026435
关键词：
Accelerometer Accident and Emergency department Activities of Daily Living Acute Adult Adverse effects Age Aging 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 Data Deceleration Development Diagnosis Disease Disease Progression Doppler Echocardiography Elderly Erythrocyte Transfusion Erythrocytes Event Failure Functional disorder Genes Healthcare Heart Heart Diseases Heart Injuries Heart failure Hemoglobin Hemoglobin SS Hemolytic Anemia Hepatic Home environment Hospitalization Hospitals Infrastructure Infusion procedures Injury to Kidney Iron Laboratories Left Lung Lung diseases Measurement Measures Meta-Analysis Microalbuminuria Morbidity - disease rate Multivariate Analysis Myocardial dysfunction Odds Ratio Operative Surgical Procedures Organ P-Selectin Pain Pathogenesis Patients Pattern Pharmaceutical Preparations Physiological Plasma Point Mutation Polymers Population Premature Mortality Prevention Probability Proteinuria Pulmonary Hypertension Pulmonary artery structure Pulse Pressure Reaction Recurrence Registries Risk Safety Sickle Cell Sickle Cell Anemia Stroke Stroke prevention Sudden Death Symptoms Systolic Pressure Testing Therapeutic Intervention Time Transfusion Treatment Efficacy Ultrasonography Universities Ventricular Visit Walking Whole Blood Exchange Transfusion acute chest syndrome beta Globin beta Thalassemia cardiovascular risk factor chronic pain chronic stroke clinical research site cohort disorder risk exercise capacity experience functional loss hazard health related quality of life hemoglobin B high risk improved improved outcome inhibitor/antagonist intervention effect lung injury meter mortality mortality risk mutant pressure prevent pro-brain natriuretic peptide (1-76)screening sildenafil standard of care therapeutic evaluation vaso-occlusive crisis

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、SCD 的所有主要心血管并发症尚无批准或共识的治疗方法患有肺动脉高压和舒张压的风险。心脏病可以通过实验室测试（NT-proBNP）和多普勒超声心动图进行非侵入性评估（估计肺动脉收缩压）最近对大约 6000 名 SCD 患者进行的荟萃分析。证明三尖瓣反流射流速度（TRV）升高的患者，这是多普勒- 超声心动图测量可估计肺动脉收缩压，步行估计在 6 分钟步行测试中，比没有升高 TRV 的人少了 30.4 米，升高 TRV 与之相关在两个大型 SCD 成年患者登记队列中，我们发现，死亡率很高（风险比为 4.9）。大约 20% 的成人 SCD 人群的两种生物标志物均具有较高值，定义为 TRV ≥ 2.5 米每秒且 NT-proBNP ≥ 160 pg/mL，并且该组的 12 个月死亡率为 7.9% 与 TRV 或 NT-proBNP 值正常的患者中的 0.5% 相比，住院风险比为 1.6. 这表明 TRV 和 NT-proBNP 的简单筛查可以识别大约 20% 的患者鉴于死亡率增加和早期丧失，SCD 的死亡和住院风险最高。与 SCD 成人心血管疾病相关的功能能力，测试有效性很重要对此类患者进行红细胞输注的治疗干预措施包括：换血，后者去除患者的血液并用输入的红细胞代替。事实证明，换血对于几乎所有 SCD 并发症的急性治疗均有效，包括严重急性胸部综合征、中风、脾脏或肝脏隔离症以及多器官衰竭长期用于预防中风和复发性急性胸部综合症。每月换血将限制疾病进展、提高运动能力并预防间隔血管闭塞性疼痛危象和急性胸部综合征的发作，导致肺动脉压力急剧增加我们建议进行一项临床试验来评估自动化的效果。与 150 名成人的护理标准相比，换血对患者发病率和死亡率的影响该试验将利用伦敦大学现有的协调中心基础设施。尽管安全且用途广泛，但匹兹堡将涉及 22 个经验丰富的临床中心。成人 SCD 患者的红细胞去除术，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。