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

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

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.

Study Overview

• Status: Completed
• Conditions: Iron Overload; Cardiomyopathy
• Intervention / Treatment: Drug: Deferoxamine and Deferiprone; Drug: Deferoxamine

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Sardinia
    • Cagliari, Sardinia, Italy, 09121
      • Adult Talassemic Center, Ospedale Microcitemico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Cardiomyopathy secondary to iron overload

Exclusion Criteria:

Heart failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Deferoxamine alone; comparison of deferoxamine subcutaneous 40mg/kg/die alone versus combined therapy deferoxamine-deferiprone	Drug: Deferoxamine and Deferiprone; 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; deferoxamine vials,40 mg/kg,12 hours/die
Active Comparator: Deferoxamine plus Deferiprone; 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; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ospedale Microcitemico
• Collaborators: Azienda Sanitaria Locale di Cagliari
• Investigators: Study Director: Maria E Lai, MD, Department of Internal Medicine, University of Cagliari-Italy

Study record dates

Study Major Dates

• Study Start: December 1, 2001
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: December 1, 2008
• First Submitted That Met QC Criteria: December 1, 2008
• First Posted (Estimate): December 2, 2008

Study Record Updates

• Last Update Posted (Estimate): December 2, 2008
• Last Update Submitted That Met QC Criteria: December 1, 2008
• Last Verified: December 1, 2001

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Heart Diseases; Iron Overload; Cardiomyopathies; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferoxamine; Deferiprone
• Other Study ID Numbers: DFO-DFP in TM; DFOplusDFPLAI