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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

Page last updated: August 20, 2015

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