Efficacy Study of the Use of Sequential DFP-DFO Versus DFP

Study Overview
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Brief Summary
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Changes in chelation treatment and transfusion practices, during the past two decades, have dramatically improved the prognosis of thalassemia major patients.Deferiprone (DFP) has been compared with deferoxamine (DFO), using different schedules of treatment, in the majority of the 13 clinical trials published between 1990 and 2008.No statistically significant difference was shown between these two interventions during, at most, 18 months of treatment.Three randomised trials that compared sequential DFP-DFO treatment versus DFO alone reported controversial results but this could be due to small sample sizes and short treatment duration. In fact, no trial with treatment duration longer than 18 months15, which reported on mortality, adverse events, serum ferritin concentrations, as well as costs has so far been published. This long-term sequential DFP-DFO treatment versus DFP alone treatment trial was conducted to assess the impacts of these chelation treatments on serum ferritin concentrations, mortality, adverse events, and costs in thalassemia major patients.

Detailed Description
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The trial was designed as a multicentre randomised open-label trial with blinded data management and data analyses, to assess whether either treatment was superior to the other. The trial was performed on behalf of the Italian Society for the study of Thalassemia and Haemoglobinopathies (SoSTE). The investigators initiated, carried out, and controlled the trial, which was conducted without influence of the non-commercial sponsor.16

Official Title
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Phase IV Study of the Use of Sequential DFP-DFO Versus DFP in Thalassemia Major Patients

Conditions
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Beta-Thalassemia, Thalassemia Major

Intervention / Treatment
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* Drug: Deferiprone (DFP) and Deferoxamine (DFO)
* Drug: Deferiprone (DFP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Thalassemia major patients with serum ferritin concentration between 800 to 3,000 ng/ml and were over 13 years of age Exclusion Criteria: Known intolerance to one of the trial treatments Platelet count < 100,000/mm3 or or leukocyte count < 3,000/mm3 Severe liver damage indicated by ascites Heart failure

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Sequential treatment including DFP at 75 mg/kg, divided into three oral daily doses, for four days per week and DFO by subcutaneous infusions (8-12h) at 50 mg/kg/day for the remaining three days per week | Drug: Deferiprone (DFP) and Deferoxamine (DFO)<br>* Sequential treatment including DFP at 75 mg/kg for four days per week and DFO by subcutaneous infusions (8-12h) at 50mg/kg/day for the remaining three days per week<br>* Other names: DFO (Biofutura Pharma S.p.A.,Italy);|
| Active Comparator: 2<br>Deferiprone alone at 75 mg/kg divided into three oral daily doses | Drug: Deferiprone (DFP)<br>* DFP alone at 75 mg/kg divided into three oral daily doses<br>* Other names: DFP (Apotex, Canada);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference between multiple observations of the serum ferritin concentrations |  | five-year treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the difference between the T2* signal at magnetic resonance imaging (MRI) of heart and liver at T0 and T1 time (see below); survival analysis; adverse events; treatment failures; and costs. |  | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thalassemia major, chelation treatment, secondary hemochromatosis