Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases
Condition: Cardiovascular Diseases; Heart Diseases; Beta-Thalassemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Thalassemia; beta-Thalassemia
Intervention: Deferoxamine; Deferiprone (L1)
Intervention description: Deferoxamine will be given daily for 12-24h/day 7 days a week either subcutaneous or intravenous at up to 50-60 mg/kg/day.; The dose of L1, 75mg/kg in three divided oral doses, is the maximum dose at which toxicity has been tested in prospective trials
Intervention MeSH terms: Deferiprone; Deferoxamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether left ventricular function improves more
      rapidly with deferoxamine (DFO) and deferiprone (L1) combination therapy than with DFO
      monotherapy in patients with thalassemia and decreased ejection fractions. Secondary aims
      include evaluating changes in myocardial iron burden using T2* and estimating the relative
      incidence and severity of chelator-induced toxicity.
    

Eligibility criteria:

        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 Exjade 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 intrauterine devices)