Sickle Cell Disease and CardiovAscular Risk - Red Cell Exchange Trial (SCD-CARRE)
SCD-CARRE
2 other identifiers
interventional
173
3 countries
23
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Feb 2020
Longer than P75 for phase_3
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2019
CompletedFirst Posted
Study publicly available on registry
September 10, 2019
CompletedStudy Start
First participant enrolled
February 26, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2026
March 4, 2026
March 1, 2026
6.3 years
August 26, 2019
March 2, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Episodes of clinical worsening
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
Secondary Outcomes (17)
Acute healthcare event
13 months
Twelve-month survival
13 months
Survival free of acute healthcare encounters
13 months
Total number of acute health care encounters
13 months
Measures of exercise capacity - 6 minute walk distance
4, 8, and 12 months
- +12 more secondary outcomes
Study Arms (2)
Exchange transfusion plus standard of care
EXPERIMENTALRandomized to standard of care and automated exchange blood transfusion every 3-6 weeks for 12 months.
Standard of care
ACTIVE COMPARATORRandomized to standard of care
Interventions
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%.
NHLBI/ASH/ATS Expert Panel recommended guidelines
Eligibility Criteria
You may qualify if:
- 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:
- Both a TRV 2.5- \<3.0 m/sec and NT-proBNP plasma level ≥ 160 pg/mL,
- TRV ≥ 3.0 m/sec,
- Both a mean pulmonary artery pressure (PAP) by right heart catheterization 20-24 mmHg and NT-proBNP plasma level ≥ 160 pg/mL,
- Mean PAP by right heart catheterization ≥ 25 mmHg,
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
University of Alabama
Tuscaloosa, Alabama, 35401, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Howard University Center for Sickle Cell Disease
Washington D.C., District of Columbia, 20060, United States
Emory University
Atlanta, Georgia, 30322, United States
University of Illinois at Chicago
Chicago, Illinois, 60607, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Johns Hopkins University
Baltimore, Maryland, 21206, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Washington University-St. Louis
St Louis, Missouri, 63110, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Montefiore Medical Center
New York, New York, 10461, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Atrium Health
Charlotte, North Carolina, 28204, United States
Duke University
Durham, North Carolina, 27708, United States
East Carolina University
Greenville, North Carolina, 27834, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Ohio State University
Columbus, Ohio, 43210, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
University of Texas Health Science Center at Houston
Houston, Texas, 77030, United States
Virginia Commonwealth University
Richmond, Virginia, 23284, United States
Hemorio
Rio de Janeiro, Brazil
Kremlin-Bicêtre
Créteil, France
Henri Mondor Hopital
Paris, France
Related Publications (1)
Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.
PMID: 40569673DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Mark Gladwin, MD
University of Maryland
- PRINCIPAL INVESTIGATOR
Darrell Triulzi, MD
University of Pittsburgh
- PRINCIPAL INVESTIGATOR
Maria Brooks, PhD
University of Pittsburgh
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Vice President for Medical Affairs, University of Maryland and Dean, University of Maryland School of Medicine
Study Record Dates
First Submitted
August 26, 2019
First Posted
September 10, 2019
Study Start
February 26, 2020
Primary Completion (Estimated)
May 31, 2026
Study Completion (Estimated)
May 31, 2026
Last Updated
March 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR
- Time Frame
- 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.
- Access Criteria
- 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.
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.