A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA)

• Published in: Blood 2014-03, Vol.123 (10), p.1447-1454
• Main Authors: Pennell, Dudley J., Porter, John B., Piga, Antonio, Lai, Yongrong, El-Beshlawy, Amal, Belhoul, Khawla M., Elalfy, Mohsen, Yesilipek, Akif, Kilinç, Yurdanur, Lawniczek, Tomasz, Habr, Dany, Weisskopf, Marianne, Zhang, Yiyun, Aydinok, Yesim
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Benzoates - administration & dosage; Benzoates - adverse effects; Benzoates - therapeutic use; beta-Thalassemia - complications; Child; Deferasirox; Deferoxamine - administration & dosage; Deferoxamine - adverse effects; Deferoxamine - therapeutic use; Female; Ferritins - blood; Heart - physiopathology; Humans; Iron - administration & dosage; Iron - metabolism; Iron Chelating Agents - administration & dosage; Iron Chelating Agents - adverse effects; Iron Chelating Agents - therapeutic use; Iron Overload - drug therapy; Iron Overload - etiology; Male; Medication Adherence; Myocardium - metabolism; Myocardium - pathology; Plenary Paper; Treatment Outcome; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - therapeutic use; Troponin T - metabolism; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-04-497842

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. •In β-thalassemia major patients with severe iron burden, deferasirox was noninferior to deferoxamine for myocardial iron removal.•The ejection fraction was stable during treatment for both deferasirox and deferoxamine.