Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases

Inclusion Criteria:

• Transfusion-dependent beta-thalassemia (eight or more transfusion episodes in the previous year)
• Left ventricular ejection fraction by MRI less than or equal to 56% by balanced steady-state free precession (SSFP) or 63% by spoiled gradient recalled echo (SPGR)
• Currently on treatment with subcutaneous or intravenous DFO; participants must be willing and able to chelate 7 days per week 12 - 24 hours per day
• Serum ferritin greater than 1000 µg/L or ferritin between 500 µg/L and 1000 µg/L and cardiac T2* less than 20 ms

Exclusion Criteria:

• Pacemaker, severe claustrophobia, or other contraindications to MRI; severe congestive heart failure (New York Heart Association Classification IV); congenital or acquired valvular heart disease significant enough to require surgery or medications
• Currently receiving treatment for hepatitis; renal insufficiency defined by a clinically significant abnormal serum creatinine with a calculated creatinine clearance of less than 50 ml/min according to the Cockroft formula
• A neutrophil count less than 1.5 x 109/L on two or more occasions at least 4 weeks apart within the past year and not associated with an acute viral illness or a platelet count less than 80 x 109/L on two or more occasions at least 4 weeks apart within the past year
• Treatment with L1 or ICL670 during the previous 2 weeks or previous adverse experience to L1 requiring suspension
• Infection with HIV
• Active participation in other investigational drug or device studies
• Unwilling to consider treatment with DFO at a dose of 50-60 mg/kg 12-24 hours per day 7 days per week
• Women who are pregnant or breast feeding
• Systemic infection or cardiovascular, hepatic, renal, pulmonary, or gastrointestinal disease that would prevent patients from undergoing any of the study-required treatments or procedures or requires treatment with any contraindicated medication(s)
• Presence of any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient's compliance with the protocol; may include but is not limited to alcohol or drug abuse
• For women of child-bearing potential, an inability or unwillingness to use a highly effective method of contraception (e.g., implants, injectables, combined oral contraceptives, or some IUDs)