Sickle Cell Disease and CardiovAscular Risk - Red Cell Exchange Trial (SCD-CARRE)

Last updated: April 24, 2025
Sponsor: University of Pittsburgh
Overall Status: Active - Not Recruiting

Phase

3

Condition

Sickle Cell Disease

Red Blood Cell Disorders

Treatment

Red Blood Cell

Standard of care

Clinical Study ID

NCT04084080
STUDY20110362
UG3HL143192
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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-selectininhibitors), 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-riskpatient:

  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 separateoccasions as defined by: macroalbuminuria (albumin to creatinine ratio (ACR) >300 mg/g) or proteinuria (protein to creatinine ratio >30 mg/mmol), orestimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. (It isrecommended that local laboratories use Chronic Kidney Disease EpidemiologyCollaboration [CKD-EPI] equation without ethnic factors when estimating andreporting 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

Exclusion Criteria:

  • RBC alloimmunization resulting in inability of blood bank to obtain compatiblecomponents for chronic exchange transfusions

  • Previous history of hyper-hemolysis syndrome

  • Previous history of severe transfusion reaction resulting in renal failure or due toserious complications such as hypotension or respiratory distress

  • More than 10 vaso-occlusive episodes in the past 12 months requiring admission to ahospital 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 medicalcondition that in the Investigator's judgement will substantially increase the riskassociated with the patient's participation in the trial

  • Women of childbearing potential who have a positive pregnancy test at baseline

Study Design

Total Participants: 173
Treatment Group(s): 2
Primary Treatment: Red Blood Cell
Phase: 3
Study Start date:
February 26, 2020
Estimated Completion Date:
May 31, 2026

Study Description

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.

Connect with a study center

  • Hemorio

    Rio De Janeiro,
    Brazil

    Site Not Available

  • Kremlin-Bicêtre

    Créteil,
    France

    Site Not Available

  • Henri Mondor Hopital

    Paris,
    France

    Site Not Available

  • Imperial College Healthcare NSH Trust-Hammersmith Hospital

    London, W12 0HS
    United Kingdom

    Site Not Available

  • University of Alabama

    Tuscaloosa, Alabama 35401
    United States

    Site Not Available

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California 94609
    United States

    Site Not Available

  • Howard University Center for Sickle Cell Disease

    Washington, District of Columbia 20060
    United States

    Site Not Available

  • Emory University

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • University of Illinois at Chicago

    Chicago, Illinois 60607
    United States

    Site Not Available

  • Johns Hopkins University

    Baltimore, Maryland 21206
    United States

    Site Not Available

  • University of Maryland

    Baltimore, Maryland 21201
    United States

    Site Not Available

  • Boston Medical Center

    Boston, Massachusetts 02118
    United States

    Site Not Available

  • Washington University-St. Louis

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Washington University-St. Louis

    St. Louis, Missouri 63110
    United States

    Site Not Available

  • Icahn School of Medicine at Mount Sinai

    New York, New York 10029
    United States

    Site Not Available

  • Montefiore Medical Center

    New York, New York 10461
    United States

    Site Not Available

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina 27599
    United States

    Site Not Available

  • Atrium Health

    Charlotte, North Carolina 28204
    United States

    Site Not Available

  • Duke University

    Durham, North Carolina 27708
    United States

    Site Not Available

  • East Carolina University

    Greenville, North Carolina 27834
    United States

    Site Not Available

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio 44106
    United States

    Site Not Available

  • Ohio State University

    Columbus, Ohio 43210
    United States

    Site Not Available

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania 15232
    United States

    Site Not Available

  • University of Texas Health Science Center at Houston

    Houston, Texas 77030
    United States

    Site Not Available

  • Virginia Commonwealth University

    Richmond, Virginia 23284
    United States

    Site Not Available

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