Combined Chelation Treatment With Deferiprone and Deferoxamine in Thalassemia Major

A Randomized, Placebo Controlled, Double Blind Trial of the Effect of Combined Therapy With Deferoxamine and Deferiprone on Myocardial Iron in Thalassemia Major Using Cardiovascular Magnetic Resonance

Thalassemia major is a genetic disorder affecting hemoglobin synthesis, rendering individuals dependent upon lifelong blood transfusions. Consequently, iron overload occurs and patients have shortened life expectancy with the most common cause of death being heart failure. This trial tests whether the combination of traditional therapy (deferoxamine) with a newer drug (deferiprone) will prove more effective in removing cardiac iron than deferoxamine alone.

Study Overview

• Status: Unknown
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Drug: deferiprone

Detailed Description

Thalassemia Major (TM) is a hereditary anemia resulting from a single gene defect that results in abnormal red cell production. The survival of affected individuals is dependent upon lifelong blood transfusions. Unfortunately, this causes total body iron overload, and 50% of the patients in the UK are dead by the age of 35. Approximately 70% of these deaths result from heart failure which results as a consequence of cardiac iron toxicity.

A Cardiovascular Magnetic Resonance (CMR) technique (which exploits the fact that T2* signal decay relates to tissue iron) developed at the Royal Brompton Hospital provides a non-invasive and reproducible assessment of cardiac iron. CMR therefore provides a very useful method to assess response to new treatments in this condition. Using cardiac T2* as a primary endpoint, we will investigate whether the oral chelator, deferiprone in combination with traditional treatment (deferoxamine), is superior in removing cardiac iron as compared to deferoxamine alone. This trial will provide the first randomized controlled, double-blinded, evidence for the efficacy of combination treatment in TM.

• Study Type: Interventional
• Enrollment: 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Sardinia
    • Cagliari, Sardinia, Italy, 09121
      • Ospedale Microcitemico, Via Jenner

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:

• Beta thalassemia major
• Maintaining pre-transfusion hemoglobin of 9 g/dL
• Myocardial T2* between 8 and 20 ms
• Ability to give informed consent
• Male or female
• Age >18 years
• Any ejection fraction
• Confirmation of effective contraception throughout the trial (both men and women)

Exclusion Criteria:

• Implant incompatible with MR (magnetic resonance), such as pacemaker, claustrophobia, or other condition making CMR impossible or inadvisable
• Neutropenia within 12 months (ANC <1.5 x10^9/L), unless normal at screening
• Thrombocytopenia within 12 months (<50 x10^9/L), unless normal at screening
• Liver enzymes > 3 times upper limit of normal
• Patients who have previously received deferiprone for a total of more than 6 months over the last 5 years.
• Patients with a previous reaction to deferiprone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Myocardial T2*

Secondary Outcome Measures

Outcome Measure
Adverse events
Liver T2*
LV and RV volumes and function in systole and diastole
Brachial artery reactivity
B-type natriuretic peptide
Patient compliance
Success of blinding

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Collaborators: CORDA, The Heart Charity; Apotex Inc.; The Cooley's Anemia Foundation,; The UK Thalassemia Society

Publications and helpful links

General Publications

• Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, Pibiri M, Nair SV, Walker JM, Pennell DJ. Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson. 2008 Feb 25;10(1):12. doi: 10.1186/1532-429X-10-12.

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Study Completion: June 1, 2005

Study Registration Dates

• First Submitted: February 14, 2005
• First Submitted That Met QC Criteria: February 14, 2005
• First Posted (Estimate): February 15, 2005

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: February 1, 2005

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Deferiprone; Deferoxamine; Iron chelation; Beta Thalassemia Major
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: 02 065