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

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ClinicalTrials.gov Identifier: NCT00115349
Recruitment Status : Terminated (due to low enrollment)
First Posted : June 22, 2005
Results First Posted : January 14, 2014
Last Update Posted : March 1, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
HealthCore-NERI

Tracking Information
First Submitted Date  ICMJE June 21, 2005
First Posted Date  ICMJE June 22, 2005
Results First Submitted Date  ICMJE May 16, 2013
Results First Posted Date  ICMJE January 14, 2014
Last Update Posted Date March 1, 2018
Study Start Date  ICMJE June 2005
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2014)
Change in Left Ventricular Ejection Fraction (LVEF). [ Time Frame: Baseline to one year ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2013)
  • Evaluate Whether L1/DFO Combination Therapy is Superior to DFO Monotherapy in Lowering Myocardial Iron Burden Estimated by Myocardial T2*. [ Time Frame: one year ]
  • Change in Left Ventricular (LV) Volume From Screening to One Year. [ Time Frame: one year ]
  • Change in ECHO LV Volume, Ejection Fraction, Shortening Fraction, and VCFc/Wall Stress Z-score From Baseline to One Year. [ Time Frame: one year ]
  • Change in Holter Monitor Scores From Baseline to One Year. [ Time Frame: one year ]
  • Initiation of or Increase in Cardiac Medications [ Time Frame: continuous ]
  • Adverse Events [ Time Frame: continous ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases
Official Title  ICMJE Thalassemia Clinical Research Network - Cardiac L1/DFO Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiovascular Diseases
  • Heart Diseases
  • Beta-Thalassemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: L1/DFO
    Deferoxamine (DFO) and deferiprone (L1) combination therapy
    Interventions:
    • Drug: Deferoxamine
    • Drug: Deferiprone (L1)
  • Active Comparator: DFO
    Deferoxamine (DFO) monotherapy
    Intervention: Drug: Deferoxamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 18, 2008)
20
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00115349
Other Study ID Numbers  ICMJE 181
U01HL065260 ( U.S. NIH Grant/Contract )
U01HL065244 ( U.S. NIH Grant/Contract )
U01HL065239 ( U.S. NIH Grant/Contract )
U01HL065238 ( U.S. NIH Grant/Contract )
U01HL065232 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party HealthCore-NERI
Study Sponsor  ICMJE HealthCore-NERI
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
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 Boston Children's Hospital
Study Chair: Elliott P, Vichinsky, MD Children's Hospital and Research Institute, Oakland
Study Chair: Sonja McKinlay, Ph.D. New England Research Institutes, Inc.
PRS Account HealthCore-NERI
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP