Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 2 months. - If patients are on hydroxyurea, glutamin, or selectin inhibitors the doses must be stable for at least 2 months prior to randomization. - Any one of the following vasculopathy biomarker clinical results (a, b, or c) measured in the 13 months before randomization that indicates a high-risk patient: 1. Both a TRV 2.5-2.9 m/sec and NT-proBNP plasma level ≥ 160 pg/mL 2. TRV ≥ 3.0 m/sec 3. Chronic kidney disease (CKD) due to SCD with macroalbuminuria (albumin creatinine ratio (ACR) >300 mg/g) on 2 occasions, or proteinuria (protein creatinine ratio >30 mg/mmol) on 2 occasions, or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 calculated on 2 occasions. - 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Exchange transfusion plus standard of care
Randomized to standard of care and automated exchange blood transfusion every 3-6 weeks for 12 months.
  • Biological: 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%.
    Other names:
    • Red blood cell (RBC)
  • Other: Standard of care
    NHLBI/ASH/ATS Expert Panel recommended guidelines
Active Comparator
Standard of care
Randomized to standard of care
  • Other: Standard of care
    NHLBI/ASH/ATS Expert Panel recommended guidelines

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Elizabeth Klings, MD
617-358-1226
klingon@bu.edu

More Details

Status
Recruiting
Sponsor
Mark Gladwin

Study Contact

Jude Jonassaint, RN
919-219-7481
jonassaintjc@upmc.edu

Detailed 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.