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: 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
• 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

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