Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases
Information source: New England Research Institutes
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiovascular Diseases; Heart Diseases; Beta-Thalassemia
Intervention: Deferoxamine (Drug); Deferiprone (L1) (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: New England Research Institutes Official(s) and/or principal investigator(s): John Porter, MD, Principal Investigator, Affiliation: University College, London Patricia J. Giardina, MD, Study Chair, Affiliation: Weill Medical College of Cornell University Ellis J. Neufeld, MD, Study Chair, Affiliation: Children's Hospital Boston Elliott P, Vichinsky, MD, Study Chair, Affiliation: Children's Hospital and Research Institute, Oakland Sonja McKinlay, Ph.D., Study Chair, Affiliation: New England Research Institutes, Inc.
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.
Clinical Details
Official title: Thalassemia Clinical Research Network - Cardiac L1/DFO Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Change in Left Ventricular Ejection Fraction (LVEF).
Secondary outcome: Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*.Change in Left Ventricular (LV) Volume From Screening to One Year. Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year. Change in Holter Monitor Scores From Baseline to One Year. Initiation of or Increase in Cardiac Medications Adverse Events
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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)
Locations and Contacts
Children's Hospital of Los Angeles, Los Angeles, California 90027, United States
Children's Hospital, Oakland, California 94609, United States
Children's Memorial Hospital, Chicago, Illinois 60614-3394, United States
Children's Hospital, Boston, Massachusetts 02115, United States
Weill Medical College of Cornell University, New York, New York 10021, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4399, United States
Additional Information
Starting date: June 2005
Last updated: January 15, 2014
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