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Phase 2 N=197 Randomized Treatment

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

Transfusional Iron Overload · Transfusional Hemosiderosis

Enrolled (actual)
197
Serious AEs
14.2%
Results posted
Aug 2014
Primary outcome: Primary: Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment — 1.12; 1.07 Millisecond

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Core Study: Deferasirox (Drug); Core Study: Deferoxamine (Drug); Extension: deferoxamine to deferasirox (Drug); Extension: deferasirox to deferoxamine (Drug); Deferasirox (Drug); Deferoxamine (Drug)
Age
Pediatric, Adult, Older Adult · 10+ yrs
Sex
All
Sponsor
Novartis Pharmaceuticals
Primary completion
Mar 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
1.12; 1.07
SECONDARY
Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
-0.5; -0.0
SECONDARY
Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
-0.95; -0.37
SECONDARY
Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment
1.04; 1.04
SECONDARY
Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
1.8; 0.88; 1.57; 0.10
SECONDARY
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)
1.81; 1.48; 1.79; 1.10
SECONDARY
Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI)
1.01; 3.32; 4.13; 5.25
SECONDARY
Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine
3; 2
SECONDARY
Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period.
65; 69; 10; 10; 1; 1
SECONDARY
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau)
2129.70
SECONDARY
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax)
150.09
SECONDARY
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data
32.25; 96.32; 136.47; 133.33; 38.66; 119.48
SECONDARY
Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment
1.06; 1.05; 1.03; 1.00; 1.17; 1.06
SECONDARY
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)
-1.1; -1.8; 0.1; -1.0; -0.5; 0.3
SECONDARY
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
1.7; 3.4; 0; 1; 1.5; -0.8
SECONDARY
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
2.0; 3.5; 0.5; 1.0; 2.0; -0.6
SECONDARY
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)
1.4; 1.8; 3.2; -6.0; 4.2; 9.1
SECONDARY
Extension Study: The Cardiac Iron Concentration From T2* Values
-0.12; -0.12; -0.08; 0; -0.38; -0.12
SECONDARY
Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
-4.56; -12.66; -6.30; -3.80; -10.22; -19.44
SECONDARY
Extension Study: Change in Serum Ferritin From Baseline by Month
-626.10; -1307.14; -1054.87; NA; -988.46; -1877.00
SECONDARY
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)
4.00

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.

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00600938). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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