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NCT Number: NCT00600938

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

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.

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Key information

Conditions

Transfusional Iron Overload Anemia Anemia, Aplastic Anemia, Diamond-Blackfan Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Hypoplastic, Congenital Anemia, Sideroblastic Bone Marrow Diseases Bone Marrow Failure Disorders Congenital Bone Marrow Failure Syndromes Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemochromatosis Hemoglobinopathies Iron Metabolism Disorders Iron Overload Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Myelodysplastic Syndromes Nutritional and Metabolic Diseases Red-Cell Aplasia, Pure Thalassemia Transfusional Hemosiderosis

Age range

10 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Toronto, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female patients, aged 10 years and above, with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study.
  • Patients with cardiac iron as measured by a myocardial T2* value that is ≥ 6ms but not ≥ 20 ms.
  • Patients with a lifetime history of at least 50 units of red cell transfusions, and must be receiving at least ≥10 units/yr of red blood cells transfusions.
  • Patients with a left ventricular ejection fraction (LVEF) ≥ 56 % as determined by cardiovascular magnetic resonance (CMR).
  • Patients with liver iron content (LIC) value ≥ 3 mg Fe / g dw, as determined by liver MRI.

Exclusion criteria

  • Patients with clinical symptoms of cardiac dysfunction.
  • Patients unable to undergo study assessments including MRI
  • Patients participating in another clinical trial or receiving an investigational drug.

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

Core Study: Deferasirox

Drug

20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day

Other names: "ICL to ICL"

Core Study: Deferoxamine

Drug

50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week

Other names: "DFO to DFO"

Extension: deferoxamine to deferasirox

Drug

40 mg/kg deferasirox once daily administered 30 minutes before taking food.

Other names: "DFO to ICL"

Extension: deferasirox to deferoxamine

Drug

DFO at a target range of 50 mg/kg/day to 60 mg/kg/day via subcutaneous (sc) infusion lasting a period of 8 to 12 hrs administered for 5 to 7 days per week,

Other names: "ICL to DFO"

Deferasirox

Drug

Deferoxamine

Drug

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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.

  2. 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

  3. Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment

    Time frame: 6 Month

    Summary statistics of T2* ratio Month 6/baseline

  4. 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)

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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)

  10. 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)

  11. 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

  12. Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment

    Time frame: Months 6, 12, 18 and 24

    The measured T2* values, the ratio (post-baseline / baseline T2*) at Month 6, 12, 18 and 24 was summarized for FAS population along with two-sided 95% CIs. The geometric means of the ratio was presented for all treatment groups

  13. Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)

    Time frame: Months 6, 12, 18 and 24

    Cardiac function endpoints (LVEF) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline

  14. Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)

    Time frame: Months 6, 12, 18 and 24

    Cardiac function endpoints (LVESVI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline

  15. Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)

    Time frame: Months 6, 12, 18 and 24

    Cardiac function endpoint (LVEDVI ) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline

  16. Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)

    Time frame: Months 6, 12, 18 and 24

    Cardiac function endpoints (LVMI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes

  17. Extension Study: The Cardiac Iron Concentration From T2* Values

    Time frame: Months 6, 12, 18 and 24

    Cardiac iron concentration (derived from T2* values) at baseline, Months 6, 12, 18 and 24 were summarized by descriptive statistics. The absolute change from baseline at Months 6, 12, 18 and 24 were also summarized by treatment group. Lliver iron concentration is expressed in units (mg of iron / g of liver tissue dry weight (dw)

  18. Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24

    Time frame: Months 6, 12, 18 and 24

    Results of liver iron content (LIC) measurements by MRI was summarized by descriptive statistics. The absolute value and the absolute change from baseline in LIC at Months 6, 12, 18 and 24 were provided by treatment group.

  19. Extension Study: Change in Serum Ferritin From Baseline by Month

    Time frame: Months 6, 12, 18 and 24

    Serum ferritin values was summarized by descriptive statistics. Absolute value and the absolute change from baseline in serum ferritin by month was provided by treatment group.

  20. Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)

    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, time to reach maximum plasma concentration (Tmax)

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: CORDELIA

Important dates

Study start
2007
Primary completion
2013
Study completion
2013
First posted
Jan 25, 2008
Registry last updated
Aug 27, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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