Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major

Study Overview
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Brief Summary
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Myocardial iron overload is the leading cause of death in patients with beta-thalassemia major (TM). Therapy with deferoxamine (DFO) combined with deferiprone (DFP) reduces myocardial iron and improves cardiac function. However, the prognosis for TM patients with established cardiac disease switched from DFO monotherapy to combined DFP/DFO chelation is unknown. Twenty-eight TM patients with cardiac disease were enrolled in a prospective study lasting 42±6 months. Fifteen (9 high-ferritin and 6 low-ferritin) were placed on DFP/DFO (DFP, 75 mg/kg t.i.d.; DFO, 40-50 mg/kg over 8-12 h at night 5-7 d/wk), while 13 (5 high- and 8 low-ferritin) received DFO alone. No cardiac events were observed among high-ferritin patients on combination therapy, whereas 4 cardiac events (p=0.0049), including three deaths, occurred in high-ferritin patients on DFO monotherapy. These findings demonstrate that in TM patients with well-established cardiac disease combined iron-chelation therapy with DFP/DFO is superior to DFO monotherapy.

Official Title
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Increased Survival and Reversion of Iron-Induced Cardiac Disease in Patients With Thalassemia Major Receiving Intensive Combined Chelation Therapy

Conditions
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Iron Overload, Cardiomyopathy

Intervention / Treatment
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* Drug: Deferoxamine and Deferiprone
* Drug: Deferoxamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiomyopathy secondary to iron overload Exclusion Criteria: Heart failure

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Deferoxamine alone<br>comparison of deferoxamine subcutaneous 40mg/kg/die alone versus combined therapy deferoxamine-deferiprone | Drug: Deferoxamine and Deferiprone<br>* comparison of two arms: the first one treated with deferoxamine subcutaneous vials,40 mg/kg,12 hours/die plus deferiprone tablets 75 mg/kg three times/die versus the second one treated with deferoxamine subcutaneous vials,40 mg/kg,12 hours/die<br>Drug: Deferoxamine<br>* deferoxamine vials,40 mg/kg,12 hours/die<br>|
| Active Comparator: Deferoxamine plus Deferiprone<br>comparison of two arms: the first one treated with deferoxamine subcutaneous vials,40 mg/kg,12 hours/die plus deferiprone tablets 75 mg/kg three times/die versus the second one treated with deferoxamine subcutaneous vials,40 mg/kg,12 hours/die | Drug: Deferoxamine and Deferiprone<br>* comparison of two arms: the first one treated with deferoxamine subcutaneous vials,40 mg/kg,12 hours/die plus deferiprone tablets 75 mg/kg three times/die versus the second one treated with deferoxamine subcutaneous vials,40 mg/kg,12 hours/die<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Our primary objective: to assess the prevalence of cardiovascular deaths and hospitalisations for cardiovascular disease in the 2 treatment groups |  | 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| monitor the left ventricular ejection fraction (LVEF) and serum ferritin levels for evidence of improvement. |  | 42 months |