Long‐term sequential deferiprone–deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial

Abstract

SummaryA multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-12 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these were randomized and underwent intention-to-treat analysis. The decrease of serum ferritin levels during the treatment period was statistically significant higher in sequential DFP-DFO patients compared with DFP-alone patients (P = 0AE005). KaplanMeier survival analysis for the two chelation treatments did not show any statistically significant differences (long-rank test, P = 0AE3145). Adverse events and costs were comparable between the groups. The trial results show that sequential DFP-DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival, adverse events, or costs. This trial was registered at http://www.clinicaltrials.gov as # NCT00733811.

Deferiprone versus Deferoxamine in Sickle Cell Disease: Results from a 5-year long-term Italian multi-center randomized clinical trial

“…Compliance was better with DFP (89%) in comparison with DFO treatment (75%) as suggested by previous clinical trials in thalassemia major patients [25] . Moreover, a similar low compliance was observed in several shorter-term SCD clinical trials of hydroxyurea [26][27][28] and during DFX long-term safety and efficacy study [13], suggesting that disease and social factors specific to SCD patient populations may contribute substantially to low study completion rates [13].…”

Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up

“…Deferasirox became commercially available during the trial; therefore, the patients who discontinued as a result of consent withdrawal or loss to follow-up may include subjects who left the study but continued to take deferasirox. The completion rate is similar to that observed in a 5-year prospective study of deferiprone-DFO combination therapy compared with deferiprone monotherapy 23 and higher than a 4-year prospective analysis of long-term deferiprone (in which dose-adjustments were not permitted by the study protocol), in which fewer than one-half of the enrolled patients completed the study. 24 Long-term deferasirox treatment led to a sustained reduction in the iron burden of the patients enrolled in the study.…”

How I treat transfusional iron overload

“…58 In Italy, a multicenter prospective randomized trial over 7 years in 265 patients found no deaths occurred in patients receiving DFP alone or in combination with DFO, whereas 10 deaths occurred in those receiving DFO alone. 59 Lai et al confirmed the superiority of combined therapy over DFO alone in treating established ironinduced cardiac disease. 60 In patients who tolerate combined therapy over several years, it is possible to reduce total body iron burden in TM to normal, assessed by serum ferritin and T2* measurement of cardiac and liver iron and to improve endocrine function.…”