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Principal Investigator: Maria Mori Brooks
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $732,050
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <21+ years old><Accelerometer><Activities of Daily Living><Activities of everyday life><Acute><Address><Adult><Adult Human><Adverse Experience><Adverse event><Aging><Alloimmunization><Amino-terminal pro-brain natriuretic peptide><Antigens><Apoplexy><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Sample><Blood erythrocyte><Blood specimen><Brain Vascular Accident><Cardiac Diseases><Cardiac Disorders><Cardiopulmonary><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Organ System><Cardiovascular Physiology><Cardiovascular system><Cell Phone><Cellular Phone><Cellular Telephone><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Certification><Cessation of life><Chronic><Chronic Kidney Failure><Chronic Renal Disease><Chronic Renal Failure><Classification><Clinical><Clinical Evaluation><Clinical Investigator><Clinical Testing><Clinical Trials><Clinical Trials Data Monitoring Committees><Collaborations><Communication><Communities><Consensus><Cross-Product Ratio><Data><Data Analytics><Data Bases><Data Collection><Data Coordinating Center><Data Coordination Center><Data Files><Data Monitoring Committees><Data Reporting><Data Set><Data and Safety Monitoring Boards><Databases><Death><Death Rate><Development><Disease Progression><Doppler Echocardiography><Doppler Study><Dysfunction><Echocardiogram><Echocardiography><Echography><Echotomography><Effectiveness><Ensure><Epidemiological data><Epidemiology data><Erythrocyte Transfusion><Erythrocytes><Erythrocytic><Event><Exclusion Criteria><Fe element><Functional disorder><Guidelines><Hb SS disease><HbSS disease><Healthcare><Heart><Heart Diseases><Heart Vascular><Hemoglobin S Disease><Hemoglobin sickle cell disease><Hemoglobin sickle cell disorder><Hemolytic Anemia><Hepatic><Home><Hospital Admission><Hospitalization><Hospitals><Human Resources><Image><Infrastructure><Infusion><Infusion procedures><Intention><Intervention><Intervention Strategies><Iron><Laboratories><Left><Lung Diseases><MOF syndrome><Manpower><Manuals><Manuscripts><Marrow erythrocyte><Measurement><Measures><Medical Ultrasound><Medical center><Meta-Analysis><Methods><Mobile Phones><Monitor><Morbidity><Morbidity - disease rate><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><N-BNP peptide><N-terminal pro-BNP><NIH><NT-BNP><NT-proBNP><National Institutes of Health><Odds Ratio><Organ><Outcome><Pain><Painful><Patients><Phase><Physiopathology><Population><Preparation><Prevention><Procedures><Process><Protocol><Protocols documentation><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Hypertension><Quality Control><Random Allocation><Random Selection><Randomized><Reaction><Recommendation><Recurrence><Recurrent><Red Blood Cell Transfusion><Red Blood Cells><Red Cell><Registries><Relative Odds><Renal function><Reporting><Research Design><Risk><Risk Ratio><Safety><Safety Monitoring Boards><Scheme><Sickle Cell Anemia><Site><Specific qualifier value><Specified><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Stroke><Stroke prevention><Study Type><Sudden Death><Symptoms><System><Systematics><Testing><Text Messaging><Therapeutic Intervention><Training><Transfusion><Transthoracic Echocardiography><Treatment Effectiveness><Ultrasonic Imaging><Ultrasonogram><Ultrasonography><Ultrasound Diagnosis><Ultrasound Medical Imaging><Ultrasound Test><Uncertainty><United States National Institutes of Health><Universities><Variant><Variation><Ventricular><Visit><Walking><Whole Blood Exchange Transfusion><Writing><accelerometry><activity monitor><activity tracker><acute chest syndrome><adjudication><adjudicative process and procedure><adulthood><bio-markers><biologic marker><biomarker><blood corpuscles><blood exchange transfusion><brain attack><cardiovascular disorder><cardiovascular function><cardiovascular risk><cardiovascular risk factor><cerebral vascular accident><cerebrovascular accident><chronic kidney disease><chronic stroke><circulatory system><clinical infrastructure><clinical research site><clinical site><clinical test><cohort><daily living function><daily living functionality><data access><data base><data centers><data management><data management and coordinating center><data management center><data quality><data representation><data representations><data sharing><death risk><design><designing><developmental><diagnostic ultrasound><disease of the lung><disease risk><disorder of the lung><disorder risk><doubt><epidemiologic data><exercise capacity><experience><functional ability><functional capacity><functional loss><hazard><health care><health related quality of life><heart disorder><heart sonography><high risk><homes><iPhone><imaging><immunogen><improved><improved outcome><inclusion criteria><infusions><intervention therapy><interventional strategy><kidney function><lung artery blood pressure><lung disorder><lung pressure><meter><mortality><mortality rate><mortality ratio><mortality risk><multiorgan failure><multiple organ system failure><operation><operations><pathophysiology><personnel><preparations><pressure in pulmonary arteries><prevent><prevent stroke><preventing><primary outcome><pro-brain natriuretic peptide (1-76)><proBNP(1-76)><pulmonary arterial blood pressure><pulmonary arterial pressure><pulmonary artery pressure><pulmonary artery systolic pressure><pulmonary pressure><randomisation><randomization><randomized, clinical trials><randomly assigned><research clinical testing><research study><right heart failure><right sided heart failure><right ventricle failure><right ventricular failure><right ventricular heart failure><screening><screenings><secondary outcome><short message service><sickle cell disease><sickle cell disorder><sickle disease><sicklemia><smart phone><smartphone><sonogram><sonography><sound measurement><standard care><standard of care><standard treatment><statistical analysis><stroked><strokes><study design><texting><therapeutically effective><ultrasound imaging><ultrasound scanning>