Key result
Combination therapy with deferoxamine and deferiprone improved left ventricular ejection fraction by 8.4% at 12 months, which was not significantly different from the 4.1% improvement with deferoxamine monotherapy (p=0.89).
Why the study?
Does combination therapy with deferoxamine and deferiprone improve LVEF compared to deferoxamine monotherapy in adults with thalassemia major and heart failure?
RCT (n=20)
Double-blind
1:1 ratio stratified by NYHA classification, permuted random blocks
Yes
Does combination therapy with deferoxamine and deferiprone improve LVEF compared to deferoxamine monotherapy in adults with thalassemia major and heart failure?
Absolute Event Rate: 8.4% vs 4.1%
p-value: p=0.89
Both deferoxamine monotherapy and combination therapy with deferiprone improved LVEF and myocardial T2* in thalassemia major patients with heart failure, though the study was underpowered to detect a difference between treatments.
Combination chelation showed no LVEF superiority versus monotherapy in this cohort; should not change practice and leaves open randomized confirmation.
BACKGROUND: Established heart failure in thalassaemia major has a poor prognosis and optimal management remains unclear. METHODS: A 1 year prospective study comparing deferoxamine (DFO) monotherapy or when combined with deferiprone (DFP) for patients with left ventricular ejection fraction (LVEF) <56% was conducted by the Thalassemia Clinical Research Network (TCRN). All patients received DFO at 50-60 mg/kg 12-24 hr/day sc or iv 7 times weekly, combined with either DFP 75 at mg/kg/day (combination arm) or placebo (DFO monotherapy arm). The primary endpoint was the change in LVEF by CMR. RESULTS: Improvement in LVEF was significant in both study arms at 6 and 12 months (p = 0.04), normalizing ventricular function in 9/16 evaluable patients. With combination therapy, the LVEF increased from 49.9% to 55.2% (+5.3% p = 0.04; n = 10) at 6 months and to 58.3% at 12 months (+8.4% p = 0.04; n = 7). With DFO monotherapy, the LVEF increased from 52.8% to 55.7% (+2.9% p = 0.04; n = 6) at 6 months and to 56.9% at 12 months (+4.1% p = 0.04; n = 4). The LVEF trend did not reach statistical difference between study arms (p = 0.89). In 2 patients on DFO monotherapy during the study and in 1 patient on combined therapy during follow up, heart failure deteriorated fatally. The study was originally powered for 86 participants to determine a 5% difference in LVEF improvement between treatments. The study was prematurely terminated due to slow recruitment and with the achieved sample size of 20 patients there was 80% power to detect an 8.6% difference in EF, which was not demonstrated. Myocardial T2* improved in both arms (combination +1.9 ± 1.6 ms p = 0.04; and DFO monotherapy +1.9 ± 1.4 ms p = 0.04), but with no significant difference between treatments (p = 0.65). Liver iron (p = 0.03) and ferritin (p < 0.001) both decreased significantly in only the combination group. CONCLUSIONS: Both treatments significantly improved LVEF and myocardial T2*. Although this is the largest and only randomized study in patients with LV decompensation, further prospective evaluation is needed to identify optimal chelation management in these high-risk patients.
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Porter et al. (2013) conducted an RCT in Thalassemia major with heart failure (n=20). Deferoxamine and deferiprone combination vs. Deferoxamine monotherapy (with placebo) was evaluated on Change in left ventricular ejection fraction (LVEF) by CMR at 12 months (p=0.89). Combination therapy with deferoxamine and deferiprone improved left ventricular ejection fraction by 8.4% at 12 months, which was not significantly different from the 4.1% improvement with deferoxamine monotherapy (p=0.89).
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