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:10402364
- 负责人:
- 金额:$ 68.06万
- 依托单位:
- 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 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccelerometerAccident and Emergency departmentActivities of Daily LivingAcuteAdultAdverse effectsAgeAlloimmunizationAntigensBiological MarkersBloodBlood capillariesCardiac Catheterization ProceduresCardiopulmonaryCardiovascular DiseasesCardiovascular PhysiologyCardiovascular systemCessation of lifeChildhood strokeChronicChronic Kidney FailureClinicalClinical TrialsCohort StudiesConsensusDecelerationDevelopmentDiagnosisDiseaseDisease ProgressionDoppler EchocardiographyElderlyErythrocytesEventFailureFunctional disorderGenesHealthcareHeart DiseasesHeart InjuriesHemoglobinHemoglobin SSHemolytic AnemiaHomeHospitalsInfusion proceduresInjury to KidneyIronLeftMeasuresMeta-AnalysisMicroalbuminuriaMorbidity - disease rateMultivariate AnalysisMyocardial dysfunctionOperative Surgical ProceduresOrganP-SelectinPainPathogenesisPatientsPatternPharmaceutical PreparationsPhysiologicalPlasmaPoint MutationPolymersPremature MortalityPreventionProbabilityProteinuriaPulmonary HypertensionPulse PressureReactionRiskSafetySickle CellSickle Cell AnemiaStrokeSudden DeathTestingTherapeutic InterventionTimeTransfusionTreatment EfficacyVentricularVisitWalkingacute chest syndromebeta Globinbeta Thalassemiacardiovascular risk factorchronic paindisorder riskexercise capacityfunctional losshazardhealth related quality of lifehemoglobin Bhigh riskimprovedinhibitorintervention effectlung injurylung pressuremetermortalitymortality riskmutantpreventpro-brain natriuretic peptide (1-76)pulmonary arterial pressureright ventricular failuresildenafilstandard of caretherapeutic evaluationtherapeutically effectivevaso-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 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.
随着镰状细胞病(SCD)患者活到成年,持续性溶血性贫血的慢性影响
随着心肺器官的逐渐发育,
功能障碍最终导致肺动脉高压,左心室舒张期心脏
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
目前还没有被认可或共识的治疗方法。患肺动脉高压和舒张压的风险
心脏病可以通过实验室检查(NT-proBNP)和多普勒超声心动图进行非侵入性评估
(估计的肺动脉收缩压)。最近一项对约6000名SCD患者进行的荟萃分析
证明了三尖瓣返流速度(TRV)升高的患者,超声心动图测量,估计肺动脉收缩压,走了估计
30.4在6分钟步行试验中,TRV升高的患者比TRV未升高的患者少3.5米,TRV升高与
死亡率高(风险比为4.9)。在两个成人SCD患者的大型登记队列中,我们发现,
大约20%的成年SCD人群的两种生物标志物值均较高,定义为TRV ≥ 2.5
米每秒和NT-proBNP ≥ 160 pg/mL,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,
1.6.这表明TRV和NT-proBNP的简单筛查谱可以识别约20%的患者
SCD患者死亡和住院的风险最高。鉴于死亡率的增加和早期丧失
与SCD成人心血管疾病相关的功能能力,重要的是要测试有效的
对这些患者进行治疗干预。红细胞输注是通过简单或
交换输血,后者将患者的血液取出,并用输注的红细胞代替。
交换输血已被证明对几乎所有SCD并发症的急性治疗有效,
严重急性胸部综合征、中风、脾或肝隔离症和多器官衰竭,
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,
每月一次的交换输血将限制疾病的进展,提高运动能力,
血管闭塞性疼痛危象和急性胸部综合征的发作,
造成右心衰竭我们建议进行临床试验,以评估自动化的效果,
与150名成年人的标准护理相比,换血对患者发病率和死亡率的影响
高危SCD患者。该试验将利用现有的协调中心基础设施在大学
匹兹堡,将涉及22个经验丰富的临床研究中心。尽管安全和广泛使用的
在成人SCD患者中使用红细胞分离术,目前还没有关于其用于
改善我们患有进行性终末器官功能障碍的老年高危SCD患者的预后。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Mark T Gladwin其他文献
Sodium Nitrite Enhances Pulmonary Epithelial Cells Wound Healing Under Normoxia via Cyclic GMPindependent Signaling Pathways
- DOI:
10.1016/j.freeradbiomed.2010.10.276 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Ling Wang;Mark T Gladwin - 通讯作者:
Mark T Gladwin
1172-74 Pulmonary hypertension is strongly associated with mortality in sickle cell disease: Comparison of echocardiographic outcome predictors
- DOI:
10.1016/s0735-1097(04)91779-2 - 发表时间:
2004-03-03 - 期刊:
- 影响因子:
- 作者:
Yukitaka Shizukuda;Vandana Sachdev;Inez Ernst;James S Nichols;Maria Jison;Bernice Brown;William Blackwelder;Griffin P Rodgers;Oswaldo Castro;Frederick P Ognibene;Jonathan P Plehn;Mark T Gladwin - 通讯作者:
Mark T Gladwin
Nitrite-NO bailout for a NOS complex too big to fail
亚硝酸盐 - 一氧化氮救助一个太大而不能倒闭的一氧化氮合酶复合物
- DOI:
10.1038/nm.2591 - 发表时间:
2011-12-06 - 期刊:
- 影响因子:50.000
- 作者:
Mark T Gladwin;Jesús Tejero - 通讯作者:
Jesús Tejero
15 - Carbonic Anhydrase Mediated Nitrite Bioactivation
- DOI:
10.1016/j.freeradbiomed.2014.10.501 - 发表时间:
2014-11-01 - 期刊:
- 影响因子:
- 作者:
Nadeem Wajih;Jun Wang;Xiaohua Liu;Christian Keggi;Amber Lee;Andrea M Belanger;Courtney Sparacino-Watkins;Mark T Gladwin;Daniel B Kim-Shapiro - 通讯作者:
Daniel B Kim-Shapiro
Nitrite as an intrinsic signaling molecule
亚硝酸盐作为一种内在信号分子
- DOI:
10.1038/nchembio1005-245 - 发表时间:
2005-10-01 - 期刊:
- 影响因子:13.700
- 作者:
Mark T Gladwin - 通讯作者:
Mark T Gladwin
Mark T Gladwin的其他文献
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{{ truncateString('Mark T Gladwin', 18)}}的其他基金
Sickle Cell Disease and Cardiovascular Risk- Red Cell Exchange SCD-CARRE
镰状细胞病和心血管风险 - 红细胞交换 SCD-CARRE
- 批准号:
10653703 - 财政年份:2022
- 资助金额:
$ 68.06万 - 项目类别:
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:
10165800 - 财政年份:2019
- 资助金额:
$ 68.06万 - 项目类别:
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 - 财政年份:2019
- 资助金额:
$ 68.06万 - 项目类别:
Antidote for inhaled CO poisoning based on mutationally engineered neuroglobin
基于突变工程神经球蛋白的吸入一氧化碳中毒解毒剂
- 批准号:
10660066 - 财政年份:2014
- 资助金额:
$ 68.06万 - 项目类别:
Antidote for inhaled CO poisoning based on mutationally engineered neuroglobin
基于突变工程神经球蛋白的吸入一氧化碳中毒解毒剂
- 批准号:
8801711 - 财政年份:2014
- 资助金额:
$ 68.06万 - 项目类别:
Antidote for inhaled CO poisoning based on mutationally engineered neuroglobin
基于突变工程神经球蛋白的吸入一氧化碳中毒解毒剂
- 批准号:
9389399 - 财政年份:2014
- 资助金额:
$ 68.06万 - 项目类别:
Antidote for inhaled CO poisoning based on mutationally engineered neuroglobin
基于突变工程神经球蛋白的吸入一氧化碳中毒解毒剂
- 批准号:
8974853 - 财政年份:2014
- 资助金额:
$ 68.06万 - 项目类别:
Training in Translational Research and Entrepreneurship in Pulmonary Vascular Biology
肺血管生物学转化研究和创业培训
- 批准号:
9906249 - 财政年份:2012
- 资助金额:
$ 68.06万 - 项目类别: