title: A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA).
abstract: Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 β-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938.
authors.affiliation: Royal Brompton Hospital, London, United Kingdom;
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: Yongrong
authors.initials: Y
authors.lastname: Lai
authors.forename: Amal
authors.initials: A
authors.lastname: El-Beshlawy
authors.forename: Khawla M
authors.initials: KM
authors.lastname: Belhoul
authors.forename: Mohsen
authors.initials: M
authors.lastname: Elalfy
authors.forename: Akif
authors.initials: A
authors.lastname: Yesilipek
authors.forename: Yurdanur
authors.initials: Y
authors.lastname: Kilinç
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lawniczek
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: Marianne
authors.initials: M
authors.lastname: Weisskopf
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005293:Ferritins / Q000097:blood; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D055118:Medication Adherence; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020107:Troponin T / Q000378:metabolism; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D020107:Troponin T; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox