Clinical trial NCT00115349: Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases
Official title: Thalassemia Clinical Research Network - Cardiac L1/DFO Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cardiovascular Diseases
Heart Diseases
Beta-Thalassemia
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2005-06-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: DESIGN NARRATIVE:

Participants will be randomized to 1 year of treatment with L1/DFO combination therapy or DFO monotherapy. At baseline, 6 months, and 1 year on therapy, cardiac function will be assessed by MRI measurement of left ventricular ejection fraction (LVEF), T2\*, Holter monitoring, and electrocardiography. Additional monitoring for safety includes weekly blood testing, monthly visits, and periodic eye and ear exams.

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)

Primary outcomes:
measure: Change in Left Ventricular Ejection Fraction (LVEF).
timeFrame: Baseline to one year
Secondary outcomes:
measure: Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*.
timeFrame: one year
measure: Change in Left Ventricular (LV) Volume From Screening to One Year.
timeFrame: one year
measure: Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year.
timeFrame: one year
measure: Change in Holter Monitor Scores From Baseline to One Year.
timeFrame: one year
measure: Initiation of or Increase in Cardiac Medications
timeFrame: continuous
measure: Adverse Events
timeFrame: continous
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: University College, London
name: John Porter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Patricia J. Giardina, MD
role: STUDY_CHAIR
affiliation: Boston Children's Hospital
name: Ellis J. Neufeld, MD
role: STUDY_CHAIR
affiliation: Children's Hospital and Research Institute, Oakland
name: Elliott P, Vichinsky, MD
role: STUDY_CHAIR
affiliation: New England Research Institutes, Inc.
name: Sonja McKinlay, Ph.D.
role: STUDY_CHAIR
References: