A Multicenter, Randomized, Open-label Phase II Trial Evaluating Deferasirox Compared With Deferoxamine in Patients With Cardiac Iron Overload Due to Chronic Blood Transfusions
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 197
- 试验地点
- 1
- 主要终点
- Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Deferasirox
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
干预措施: Deferasirox (Drug)
Deferasirox Placebo
50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week
干预措施: Deferoxamine (Drug)
结局指标
主要结局
Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
时间窗: 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)
次要结局
- Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment(6 Month)
- 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)(6 Month, 12 Month)
- Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI)(6 Month, 12 Month)
- Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine(12 Month)
- Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)(Months 6, 12, 18 and 24)
- Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24(Months 6, 12, 18 and 24)
- Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)(6 Month)
- Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period.(12 Month)
- Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau)(12 Month)
- Extension Study: The Cardiac Iron Concentration From T2* Values(Months 6, 12, 18 and 24)
- Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)(12 Month)
- Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)(6 Month, 12 Month)
- Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)(Months 6, 12, 18 and 24)
- Extension Study: Change in Serum Ferritin From Baseline by Month(Months 6, 12, 18 and 24)
- Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)(12 Month)
- Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax)(12 Month)
- Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment(Months 6, 12, 18 and 24)
- Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)(Months 6, 12, 18 and 24)
- Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data(Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose))
- Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)(Months 6, 12, 18 and 24)