The Use of the Calcium Channel Blocker Amlodipine as an Adjuvant Treatment to Iron Chelation for the Prevention of Iron Overload Cardiomyopathy in Patients With Thalassemia
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in cardiac T2*
研究概览
简要总结
This is a randomized, open label, two arms superiority trial of a representative population of patients with a primary diagnosis of transfusion dependent thalassemia with evidence of moderate cardiac iron overload, defined as an average T2* MRI parameter at the mid inter-ventricular septum between 10 and 20ms.
详细描述
Selection of Study Population: The study will enroll 60 adult subjects with transfusion dependent thalassemia receiving deferasirox iron chelation therapy. All eligible subjects will be asked to provide informed consent before participating in the study.
Randomization: Subjects will be randomized in a 1:1 ratio to either continuation of their DFX (control arm) or a combination of DFX plus amlodipine (amlodipine arm).
Treatment: Subjects randomized to the amlodipine arm will receive open label medication (amlodipine) starting at 2.5mg/day and up-titrated by 2.5mg every 7-14 days with the goal of reaching 10mg/day. DFX dose in either arm will not be adjusted unless it was deemed unsafe to remain on the same dose of DFX by the treating physician (significant side effects, lack of efficacy or over-chelation) or T2* drops below 8 ms.
Safety Assessment: Weekly or fortnightly amlodipine titration will be conducted by the research physician in-clinic, based on blood pressure, tolerability, and presence or absence of side-effects.
Adverse Events will be assessed at every visit after the first dose through to the last subject visit.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of transfusion-dependent Thalassemia being followed by a thalassemia comprehensive care clinic Age 18 or older
- •Taking deferasirox and on a stable dose for >3 months
- •Evidence on cardiac MRI of mild to moderate cardiac iron overload (T2*<20ms but ≥10ms) as measured within 3 months prior to randomization. If a recent cardiac MRI has not been obtained, patients who otherwise meet all eligibility criteria and provide appropriate consent will undergo a cardiac MRI to confirm eligibility
- •Preserved left ventricular ejection fraction (LVEF) >55% as measured by cardiac MRI. If a recent cardiac MRI has not been obtained, patients who otherwise meet all eligibility criteria and provide appropriate consent will undergo a cardiac MRI to confirm eligibility.
- •Agreeable to use an approved method of contraception if female of childbearing potential for the entire duration of the study.
排除标准
- •Serum ferritin < 500 ng/mL at screening
- •Liver iron concentration > 30 mg/g dw as measured by liver R2 MRI (FerriScan)
- •Congestive heart failure
- •Severe refractory Hypotension (less than 90 mmHg systolic)
- •Currently taking any calcium channel blockers
- •Pregnancy or nursing (a negative HCG (pregnancy) test must be obtained prior to randomization)
- •As a result of medical review, physical examination or screening investigations, the Principal Investigator (PI) considers the subject unfit for the study
- •No fixed address
- •Hypersensitivity to amlodipine or other dihydropyridines
研究组 & 干预措施
Deferasirox plus amlodipine
deferasirox iron chelation therapy with amlodipine
干预措施: Deferasirox (Drug)
Deferasirox
deferasirox iron chelation therapy and standard of care by the treating physician
干预措施: Deferasirox (Drug)
Deferasirox plus amlodipine
deferasirox iron chelation therapy with amlodipine
干预措施: Amlodipine (Drug)
结局指标
主要结局
Change in cardiac T2*
时间窗: 12 months following randomization
Change in cardiac T2\* as determined by MRI
次要结局
- Change in left ventricular ejection fraction(12 months following randomization)
- Number of Participants with Adverse Events(12 months following randomization)
研究者
Kevin H.M. Kuo, MD, MSc, FRCPC
Assistant Professor
University Health Network, Toronto