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.

Figures

Figure 1

Patient disposition. †A patient could have multiple reasons for screening failure or exclusion from efficacy analysis. ‡These patients comprised the safety set. §Efficacy was assessed using the per-protocol analysis set. ||Because of worsening of cardiac T2* in 3 deferasirox patients and 3 DFO patients, LVEF decreased <50% in 1 DFO patient and cardiomegaly in 1 deferasirox patient.

Figure 2

Gmean myocardial T2* in patients treated with deferasirox or DFO for 1 year. Values are for (A) all patients or patients with (B) baseline myocardial T2* <10 milliseconds, (C) baseline myocardial T2* ≥10 milliseconds, (D) baseline LIC <7 mg Fe/g dw, (E) baseline LIC 7 to <15 mg Fe/g dw, or (F) baseline LIC ≥15 mg Fe/g dw. All panels are based on the per-protocol population.

Figure 3

Shift in proportion of patients with severe, mild-to-moderate, and normalized cardiac T2* values at baseline and EOS. Values are for patients treated with (A) deferasirox or (B) DFO for 1 year. Both panels are based on the per-protocol population.