此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

镰状细胞病和心血管风险 - 红细胞交换试验 (SCD-CARRE) (SCD-CARRE)

2026年11月5日 更新者：Mark Gladwin、University of Pittsburgh

The SCD-CARRE trial is a Phase 3, prospective, randomized, multicenter, controlled, parallel two-arm study aimed to determine if automated exchange blood transfusion and standard of care administered to high mortality risk adult SCD patients reduces the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/hospital visits) or resulting in death over 12 months as compared with standard of care.

研究概览

地位

完全的

条件

干预/治疗

详细说明

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, the investigators 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 the investigators 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.

The investigators 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.

研究类型

介入性

注册 (实际的)

173

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 巴西
      • Rio de Janeiro、巴西
        • Hemorio
  • 法国
      • Créteil、法国
        • Kremlin-Bicêtre
      • Paris、法国
        • Henri Mondor Hopital
  • 美国
    • Alabama
      • Tuscaloosa、Alabama、美国、35401
        • University of Alabama
    • California
      • Oakland、California、美国、94609
        • UCSF Benioff Children's Hospital Oakland
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20060
        • Howard University Center for Sickle Cell Disease
    • Georgia
      • Atlanta、Georgia、美国、30322
        • Emory University
    • Illinois
      • Chicago、Illinois、美国、60607
        • University of Illinois at Chicago
    • Maryland
      • Baltimore、Maryland、美国、21201
        • University of Maryland
      • Baltimore、Maryland、美国、21206
        • Johns Hopkins University
    • Massachusetts
      • Boston、Massachusetts、美国、02118
        • Boston Medical Center
    • Missouri
      • St Louis、Missouri、美国、63110
        • Washington University-St. Louis
    • New York
      • New York、New York、美国、10029
        • Icahn School of Medicine at Mount Sinai
      • New York、New York、美国、10461
        • Montefiore Medical Center
    • North Carolina
      • Chapel Hill、North Carolina、美国、27599
        • University of North Carolina at Chapel Hill
      • Charlotte、North Carolina、美国、28204
        • Atrium Health
      • Durham、North Carolina、美国、27708
        • Duke University
      • Greenville、North Carolina、美国、27834
        • East Carolina University
    • Ohio
      • Cleveland、Ohio、美国、44106
        • University Hospitals Cleveland Medical Center
      • Columbus、Ohio、美国、43210
        • Ohio State University
    • Pennsylvania
      • Pittsburgh、Pennsylvania、美国、15232
        • University of Pittsburgh Medical Center
    • Texas
      • Houston、Texas、美国、77030
        • University of Texas Health Science Center at Houston
    • Virginia
      • Richmond、Virginia、美国、23284
        • Virginia Commonwealth University

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Age 18 years or older

  • Diagnosis of SCD: homozygous sickle cell disease, hemoglobin-SC, Sβ-thalassemia, hemoglobin-SO or hemoglobin-SD.

  • Patients not on a chronic exchange transfusion program for at least 60 days.

  • If patients are on a SCD drug (e.g. hydroxyurea, glutamine, or P-selectin inhibitors), the doses must be stable for at least 60 days prior to randomization. At the time of randomization, participants must be off Oxbryta for at least 30 days.

  • Any one of the following vasculopathy biomarker clinical results (a, b, c, d or e) measured in the last 24 months before randomization that indicates a high-risk patient:

    1. Both a TRV 2.5- <3.0 m/sec and NT-proBNP plasma level ≥ 160 pg/mL,
    2. TRV ≥ 3.0 m/sec,
    3. Both a mean pulmonary artery pressure (PAP) by right heart catheterization 20-24 mmHg and NT-proBNP plasma level ≥ 160 pg/mL,
    4. Mean PAP by right heart catheterization ≥ 25 mmHg,
    5. Chronic kidney disease (CKD) due to SCD with abnormal measures on 2 separate occasions as defined by: macroalbuminuria (albumin to creatinine ratio (ACR) >300 mg/g) or proteinuria (protein to creatinine ratio >30 mg/mmol), or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. (It is recommended that local laboratories use Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation without ethnic factors when estimating and reporting GFR).

Clinical results of these biomarkers measured locally at sites within 24 months prior to randomization are acceptable to determine eligibility. TRV, PAP, NT-proBNP, albumin to creatinine ratio, protein to creatinine ratio, or eGFR values must be measured in a steady state (defined as measured ≥ 14 days since an acute care pain event) on different days.

vi. Written informed consent obtained from patient to participate in the trial.

Exclusion Criteria:

  • RBC alloimmunization resulting in inability of blood bank to obtain compatible components for chronic exchange transfusions
  • Previous history of hyper-hemolysis syndrome
  • Previous history of severe transfusion reaction resulting in renal failure or due to serious complications such as hypotension or respiratory distress
  • More than 10 vaso-occlusive episodes in the past 12 months requiring admission to a hospital to receive treatment.
  • Religious objection to receiving blood transfusion
  • Diagnosis of ischemic stroke within the past 6 months
  • Clinical evidence of liver failure or advanced cirrhosis or any co-existing medical condition that in the Investigator's judgement will substantially increase the risk associated with the patient's participation in the trial
  • Women of childbearing potential who have a positive pregnancy test at baseline

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：单身的

武器和干预

参与者组/臂
干预/治疗
实验性的：Exchange transfusion plus standard of care

Randomized to standard of care and automated exchange blood transfusion every 3-6 weeks for 12 months.
生物：Red Blood Cell

Red blood cell exchange transfusions will be performed every 3-6 weeks to maintain a target post-transfusion hemoglobin S level of <20% and a pre-transfusion hemoglobin S of <30%.

其他名称：
  • 红细胞 (RBC)
其他：Standard of care

NHLBI/ASH/ATS Expert Panel recommended guidelines
有源比较器：Standard of care

Randomized to standard of care
其他：Standard of care

NHLBI/ASH/ATS Expert Panel recommended guidelines

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Episodes of clinical worsening
大体时间：13 months

The efficacy of the intervention will be measured by comparing the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/Hospital visits) or resulting in death over 13 months between groups.
13 months

次要结果测量

结果测量
措施说明
大体时间
Acute healthcare event
大体时间：13 months

A 6-level prioritized rank-based outcome: 1.No death or SCD-related acute health care encounters (SCDAcuteE) within (w/in) 13 months (m) of randomization; 2. Had SCDAcuteE but NO major complications (acute kidney injury (AKI), acute chest syndrome (ACS), cor pulmonale, stroke, liver failure) associated with an SCDAcuteE nor death w/in 13 m of randomization; 3. Had 1 major complication (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with an SCDAcuteE but not death w/in 13 m of randomization; 4. Had 2 major complications (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with SCDAcuteE but not death w/in 13 m of randomization; 5. Had ≥ 3 major complications (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with SCDAcuteE but not death w/in 13 m of randomization; 6.Death w/in 13 m of randomization. If the same complication reoccurs, occurrences will be counted as separate complications if the acute health care encounters are separated by ≥7 days.
13 months
Twelve-month survival
大体时间：13 months

Survival over thirteen-month period will be analyzed and compared between the group receiving the intervention and the group receiving care routinely provided for sickle cell patients based on the NHLBI guidelines.
13 months
Survival free of acute healthcare encounters
大体时间：13 months

Survival free of acute health care encounters over 13 months.
13 months
Total number of acute health care encounters
大体时间：13 months

The total number of acute health care encounters (non-elective infusion center/ER/Hospital visits) with evidence of cor pulmonale (physical exam findings, NT-proBNP increase plus echocardiographic evidence of worsening right heart function).
13 months
Measures of exercise capacity - 6 minute walk distance
大体时间：4, 8, and 12 months

Measures of exercise capacity assessed at 4, 8 and 12 months by the distance walked in the six minute walk distance assessment
4, 8, and 12 months
Measures of exercise capacity - outpatient activity
大体时间：4, 8, and 12 months

Measures of exercise capacity assessed at 4, 8 and 12 months by the distance walked in a 7 day in the outpatient setting.
4, 8, and 12 months
Cardiovascular risk
大体时间：12 months

Established cardiovascular risk biomarkers and indices are combined to help the investigators form an opinion about cardiovascular risks. The following will be measured: NT-proBNP, QT prolongation, systemic pulse pressure, albuminuria, estimated GFR and CKD progression Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group criteria.
12 months
Development of new leg ulcers
大体时间：4, 8 and 12 months

Participants will be assessed for development of new leg ulcers at each physical exam.
4, 8 and 12 months
Measures of exercise capacity - WHO Classification
大体时间：4, 8 and 12 months

WHO functional status severity will be measured assessing by looking at limitation of usual physical activity from I (no limitation in usual physical activity) to Class IV (inability to perform any physical activity at rest)
4, 8 and 12 months
Nocturnal desaturation
大体时间：4, 8 and 12 months

Nocturnal desaturation will measured using a wearable device to measure blood oxygen saturation for 7 nights at home.
4, 8 and 12 months
SCD specific patient reported outcomes - Pain
大体时间：4, 8 and 12 months

SCD specific patient reported outcomes as measured by self-reported pain
4, 8 and 12 months
SCD specific patient reported outcomes -Quality of Life modified PROMIS scale
大体时间：4, 8 and 12 months

SCD specific patient reported outcomes as measured by a modified version of health related quality of life questionnaire from PROMIS QoL measure
4, 8 and 12 months
SCD specific patient reported outcomes -Quality of Life modified ASCQ-Me scale
大体时间：4, 8 and 12 months

SCD specific patient reported outcomes as measured by a modified version of health related quality of life questionnaire from ASCQ-Me QoL measure
4, 8 and 12 months
Cardiovascular function by echocardiography - TRV
大体时间：4, 8 and 12 months

Cardiovascular function measures from echocardiography assessed at 4, 8 and 12 months: echocardiographic measures of tricuspid regurgitant jet velocity in m/s.
4, 8 and 12 months
Cardiovascular function by echocardiography - diastolic left heart function
大体时间：4, 8 and 12 months

Diastolic left heart function measured by E/A ratio, E/Em ratio, and deceleration times will be assessed by echocardiography.
4, 8 and 12 months
Cardiovascular function by echocardiography - systolic right heart function
大体时间：4, 8 and 12 months

Systolic right heart health will be measured by assessing tricuspid annular plane systolic excursion (TAPSE), right ventricular size and contractility from echocardiography of the heart.
4, 8 and 12 months
Total number of acute health care encounters
大体时间：13 months

The number of acute health care encounters (non-elective infusion center/ER/Hospital visits) with at least one major complication.
13 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University of Pittsburgh

合作者

National Heart, Lung, and Blood Institute (NHLBI)

调查人员

  • 首席研究员：Maria Brooks, PhD、University of Pittsburgh
  • 学习椅：Mark Gladwin, MD、University of Maryland
  • 首席研究员：Darrell Triulzi, MD、University of Pittsburgh

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2020年2月26日

初级完成 (实际的)

2026年5月11日

研究完成 (实际的)

2026年10月31日

研究注册日期

首次提交

2019年8月26日

首先提交符合 QC 标准的

2019年9月9日

首次发布 (实际的)

2019年9月10日

研究记录更新

最后更新发布 (实际的)

2026年11月10日

上次提交的符合 QC 标准的更新

2026年11月5日

最后验证

2026年11月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • STUDY20110362
  • UG3HL143192 (美国 NIH 拨款/合同)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

Results from research conducted under this project will be shared in several ways. Manuscripts will be submitted for publication in high-quality peer-reviewed journals, following the NIH Public Access Policy guidelines. Findings will be presented at relevant national conferences, public lectures, scientific institutions and meetings. The timeline for participant recruitment, data collection and analysis will foster publication, facilitated by the investigators' Publications Committee, of critically important and clinically relevant data throughout the trial. The study datasets will be archived and made available to qualified individuals after a period of exclusive use by the SCD-CARRE trial research team and after publication of the primary manuscripts, following NIH guidelines.

IPD 共享时间框架

At the end of the trial, study de-identified datasets will be submitted for permanent archive in the NHLBI BioLINCC repository. The trial will also produce deliverables that will be freely available to the sickle cell community including a description of the protocol for automated red blood cell exchange transfusion.

IPD 共享访问标准

All publications based on the SCD-CARRE trial will adhere to the NIH Public Access Policy (Notice NOT-OD-08-033). All study data will be de-identified. At the end of the trial, study de-identified datasets will be submitted for permanent archive in the NHLBI BioLINCC repository.

The investigators also will work closely with regional and National SCD Foundations to promote recruitment for this study and communicate our results.

IPD 共享支持信息类型

  • 企业社会责任

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅