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

Korábbi kezelés

• 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
• Religious objection to receiving blood transfusion

Más betegség

• 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

Egyéb

• RBC alloimmunization resulting in inability of blood bank to obtain compatible components for chronic exchange transfusions
• More than 10 vaso-occlusive episodes in the past 12 months requiring admission to a hospital to receive treatment.
• Women of childbearing potential who have a positive pregnancy test at baseline

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