Clinical Trial: Evaluating Use of Deferasirox as Compared to Deferoxamine in Treating Cardiac Iron Overload

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multicenter, Randomized, Open-label Phase II Trial Evaluating Deferasirox Compared With Deferoxamine in Patients With Cardiac Iron Overload Due to Chronic Blood Transfusions

Brief Summary:

This is a clinical research study in patients who have iron overload in the heart due to chronic blood transfusions.

The study will have 2 treatment groups and will compare the safety and efficacy of chelation therapy with a medicine called deferasirox (ICL670) with another medicine called deferoxamine (DFO). The study is aimed at finding out which of the two medicines is the best for treating iron overload in the heart.

Patients will be treated for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study treatment in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the heart and the liver will be evaluated using specific magnetic resonance imaging (MRI) assessments.


Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment [ Time Frame: 12 Month ]

Non- inferiority in efficacy of deferasirox compared to deferoxamine (DFO) in treating cardiac iron overload as measured by T2*. A non-inferiority margin of 0.9 (90%) was applied. Due to limitations in performing heart biopsies, T2* (T2 star), a Magnetic Resonance (MR) relaxation parameter expressed in milliseconds, as is an important tool to noninvasively quantify cardiac iron concentration. Studies have shown that myocardial T2* evaluations may predict cardiac events, e.g., impaired (<56%) left ventricular ejection fraction (LVEF) is prevalent among patients with low T2*: found in 62% of patients with T2*<8 ms; 20% with T2* of 8-12 ms; and in 5% with T2* >12 ms (Tanner 2006)


Original Primary Outcome: Relative change from baseline in myocardial T2* after 12 months treatment with deferasirox versus deferoxamine.

Current Secondary Outcome:

  • Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 12 Month ]
    An absolute change from baseline in LVEF after 12 months treatment with deferasirox and compared to.DFO was tested using an analysis of covariance model including baseline left ventricular ejection fraction (LVEF) as a covariate.
  • Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 6 Month ]
    An absolute change from baseline in LVEF after 6 months treatment with deferasirox and DFO was summarized
  • Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment [ Time Frame: 6 Month ]
    Summary statistics of T2* ratio Month 6/baseline
  • Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI) [ Time Frame: 6 Month, 12 Month ]
    An absolute change from baseline in LVESVI after 6 and 12 months treatment with deferasirox and DFO was summarized. Changes in cardiovascular magnetic resonance (CMR) measured left ventricular end systolic after 6 and 12 months treatment. Left ventricular (LV) end-systolic volume indexed to body surface area (ESVI) is a simple yet powerful echocardiographic marker of LV remodeling that can be measured easily. Left ventricular (LV) end-systolic volume (ESV) has been shown to be an important determinant of survival after myocardial infarction (MI)
  • Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) [ Time Frame: 6 Month, 12 Month ]
    An absolute change from baseline in LVEDVI after 6, and 12 months treatment with deferasirox and DFO was summarized
  • Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI) [ Time Frame: 6 Month, 12 Month ]
    An absolute change from baseline in LVMI after 6, and 12 months treatment with deferasirox and DFO was summarized
  • Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine [ Time Frame: 12 Month ]
    The number of patients withdrawn from the study due to LVEF <50%, T2* <6 ms or significant decreases in T2* ≥ 33% from baseline was provided per treatment group.
  • Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. [ Time Frame: 12 Month ]
    Number of patients with adverse events, serious adverse events and death
  • Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau) [ Time Frame: 12 Month ]
    The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, area under the plasma concentration-time curve for a dosing interval (AUCtau)
  • Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax) [ Time Frame: 12 Month ]
    The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, maximum plasma concentration (Cmax)
  • Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data [ Time Frame: Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose) ]
    The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. For trough concentration assessments, a 2-mL blood sample was to be taken on arrival at the study site, i.e. prior to the patient receiving the daily deferasirox dose (pre-dose blood sample). A second 2-mL blood sample was to be taken 2 hours later (post-dose sample). At all other visits (Visits 3 - 14), a pre-dose sample was to be taken. For PK profile assessments, 3 blood samples were taken after 1, 2, and 4 hours post-dose in addition to the 2-mL pre-dose
  • Extension Study: Change From Baseline in Myocardial T2* After 24 Months Tr

    Original Secondary Outcome: • Absolute and relative change from baseline in liver iron content (LIC) by liver MRI, and serum ferritin after 6 and 12 months treatment with deferasirox vs. deferoxamine

    Information By: Novartis

    Dates:
    Date Received: January 14, 2008
    Date Started: November 2007
    Date Completion:
    Last Updated: August 13, 2014
    Last Verified: August 2014