Combined Chelation Treatment With Deferiprone and Deferoxamine in Thalassemia Major

Sponsor

Royal Brompton & Harefield NHS Foundation Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT00103753

Collaborator

CORDA, The Heart Charity (Other), The Cooley's Anemia Foundation, (Other), Apotex Inc. (Industry), The UK Thalassemia Society (Other)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Beta-Thalassemia	Drug: deferiprone	Phase 4

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2004

Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Myocardial T2* []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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