Combined Chelation Treatment With Deferiprone and Deferoxamine in Thalassemia Major - Full Text View

Sponsors and Collaborators:	Royal Brompton & Harefield NHS Foundation Trust CORDA, The Heart Charity The Cooley’s Anemia Foundation, Apotex Inc. The UK Thalassemia Society
Information provided by:	Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00103753

Purpose

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	Intervention	Phase
Beta-Thalassemia	Drug: deferiprone	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study
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

Resource links provided by NLM:

Genetics Home Reference related topics: beta thalassemia

MedlinePlus related topics: Thalassemia

Drug Information available for: Deferoxamine 1,2-Dimethyl-3-hydroxypyrid-4-one Deferoxamine mesylate

U.S. FDA Resources

Further study details as provided by Royal Brompton & Harefield NHS Foundation Trust:

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

Estimated Enrollment:	65
Study Start Date:	May 2004
Estimated Study Completion Date:	June 2005

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103753

Locations

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

Sponsors and Collaborators

Royal Brompton & Harefield NHS Foundation Trust

CORDA, The Heart Charity

The Cooley’s Anemia Foundation,

Apotex Inc.

The UK Thalassemia Society

More Information

No publications provided by Royal Brompton & Harefield NHS Foundation Trust

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

Study ID Numbers:	02 065
Study First Received:	February 14, 2005
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00103753 History of Changes
Health Authority:	United Kingdom: National Health Service

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:

Randomized Controlled Trial
Deferiprone
Deferoxamine
Iron chelation
Beta Thalassemia Major

Study placed in the following topic categories:

Hematologic Diseases
Deferiprone
Beta-thalassemia
Anemia
Anemia, Hemolytic
Thalassemia
Anemia, Hemolytic, Congenital
Thalassemia Minor

Genetic Diseases, Inborn
Beta-Thalassemia
Hemoglobinopathies
Chelating Agents
Hemoglobinopathy
Iron
Deferoxamine

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Hematologic Diseases
Deferiprone
Anemia
Iron Chelating Agents
Anemia, Hemolytic
Thalassemia
Pharmacologic Actions

Siderophores
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Beta-Thalassemia
Hemoglobinopathies
Chelating Agents
Deferoxamine

ClinicalTrials.gov processed this record on September 11, 2009