Clinical trial NCT00103753: Combined Chelation Treatment With Deferiprone and Deferoxamine in Thalassemia Major
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Beta-Thalassemia
Keywords: Randomized Controlled Trial
Deferiprone
Deferoxamine
Iron chelation
Beta Thalassemia Major
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: CORDA, The Heart Charity
name: The Cooley's Anemia Foundation,
name: Apotex Inc.
name: The UK Thalassemia Society
First posted: 2005-02-15
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Myocardial T2*
Secondary outcomes:
measure: Liver T2*
measure: LV and RV volumes and function in systole and diastole
measure: Brachial artery reactivity
measure: B-type natriuretic peptide
measure: Patient compliance
measure: Adverse events
measure: Success of blinding
Other outcomes:
Locations:
city: Cagliari
country: Italy
facility: Ospedale Microcitemico, Via Jenner
state: Sardinia
Study officials:
References:
citation: 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.