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

This study has been terminated.
(due to low enrollment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00115349
First received: June 21, 2005
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Cardiovascular Diseases
Heart Diseases
Beta-Thalassemia
Drug: Deferoxamine
Drug: Deferiprone (L1)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Thalassemia Clinical Research Network - Cardiac L1/DFO Trial

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • Change in Left Ventricular Ejection Fraction (LVEF). [ Time Frame: Baseline to one year ] [ Designated as safety issue: Yes ]
    The primary outcome variable is change in left ventricular ejection fraction (blood ejected from the heart into the body) as measured by MRI from baseline to one year. The unit of primary outcome (left ventricular ejection fraction) is the percent of the blood in left ventricle.


Secondary Outcome Measures:
  • Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Change in Left Ventricular (LV) Volume From Screening to One Year. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Change in Holter Monitor Scores From Baseline to One Year. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Initiation of or Increase in Cardiac Medications [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • Adverse Events [ Time Frame: continous ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: June 2005
Study Completion Date: April 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Deferoxamine (DFO) and deferiprone (L1) combination therapy
Drug: Deferoxamine
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.
Other Name: DFO
Drug: Deferiprone (L1)
The dose of L1, 75mg/kg in three divided oral doses, is the maximum dose at which toxicity has been tested in prospective trials
Other Name: L1
Active Comparator: 2
Deferoxamine (DFO) monotherapy
Drug: Deferoxamine
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.
Other Name: DFO

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00115349

Locations
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital
Oakland, California, United States, 94609
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614-3394
United States, Massachusetts
Children's Hospital
Boston, Massachusetts, United States, 02115
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4399
Sponsors and Collaborators
New England Research Institutes
Investigators
Principal Investigator: John Porter, MD University College, London
Study Chair: Patricia J. Giardina, MD Weill Medical College of Cornell University
Study Chair: Ellis J. Neufeld, MD Children's Hospital Boston
Study Chair: Elliott P, Vichinsky, MD Children's Hospital and Research Institute, Oakland
Study Chair: Sonja McKinlay, Ph.D. New England Research Institutes, Inc.
  More Information

No publications provided

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00115349     History of Changes
Other Study ID Numbers: 181, U01HL065260, U01HL065244, U01HL065239, U01HL065238, U01HL065232, U01 HL65232, U01 HL65238, U01 HL65239, U01 HL65244, U01 HL65260
Study First Received: June 21, 2005
Results First Received: May 16, 2013
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Beta-Thalassemia
Cardiovascular Diseases
Heart Diseases
Thalassemia
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Deferiprone
Deferoxamine
Chelating Agents
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents
Siderophores

ClinicalTrials.gov processed this record on November 20, 2014