Effect of L-type Calcium Channel Blocker (Amlodipine) on Myocardial Iron Deposition in Thalassemic Patients With Moderate to Severe Myocardial Iron Deposition: A Randomized Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Efficacy of amlodipine in retarding rate of myocardial iron deposition (Assessed by change in T2* times)
研究概览
简要总结
Children with thalassemia may have high iron levels after receiving blood transfusions. These high iron levels can have damaging effects on the body, especially the heart. Conventionally only chelation therapy was given for prevention of iron buildup in the heart. However, current research has shown that another drug, amlodipine, also helps to slow down the deposition of iron in the heart. This study is designed to see if patients receiving amlodipine along with their regular chelation therapy have a slower rate of iron buildup in the heart when compared with patients who are receiving chelation only.
详细描述
Null Hypothesis There is no difference between the efficacy of chelation plus amlodipine therapy and chelation therapy alone in retarding the rate of myocardial iron deposition in thalassemia patients with iron overload and a constant transfusion need.
Alternate Hypothesis Chelation plus amlodipine therapy is more efficacious than chelation therapy alone in retarding the rate of myocardial iron deposition in thalassemia patients with iron overload and a constant transfusion need.
The aim of the investigators study is to determine if amlodipine, an L-type specific calcium channel blocker, in addition to the standard aggressive chelation therapy, can retard the deposition of iron in the myocardium of thalassemia patients with significant myocardial iron load with or without cardiomyopathy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric patients aged ≥ 6 and ≤ 20 years managed at AKUH for at least 1 year
- •≥ 10 blood transfusion in life time
- •Transfusion need ≥ 180 ml/kg/year
- •Serum ferritin ≥ 1000 ug/dl
- •Patient deemed capable of receiving chelation therapy (by treating hematologist) either subcutaneous infusion of Deferoxamine (Desferal) (3-5 days a week) or oral deferasirox (daily) or Defeperione (oral) or a combination of Desferal and Defeperione.
- •Patients who have been on a stable chelation regimen ≥ 6 months
- •Completed and signed Informed consent/assent.
排除标准
- •Patients with known hypersensitivity to amlodipine.
- •Patients with known sinoatrial nodal disease or aortic stenosis.
- •Patients with known severe myocardial dysfunction, defined as A LV ejection fraction of ≤ 4 SD for age even without symptoms.
- •Patients with known signs and symptoms of heart failure.
- •Patients with a T2* value of < 4 ms on cardiac MRI.
- •Patients with systolic blood pressures ≤ 2 SD for age (systemic hypotension) at the time of enrolment.
- •Patients with previously diagnosed significant congenital heart diseases or acquired heart diseases other than thalassemia (as defined earlier).
- •Patients with known contraindications to MRI (pacemakers, cerebral aneurysm metal clips, etc.)
- •Patient with a known history of developing tetany after use of a calcium channel blocker
- •Known pregnancy.
研究组 & 干预措施
Standard Chelation & Amlodipine
This arm will receive both chelation and amlodipine.
Amlodipine will be administered as a single daily dose. It will be administered at a dose of 0.1 mg/kg/day or maximum of 2.5 mg/day.
Standard Chelation therapy will be administered either by subcutaneous infusion of Deferoxamine (3-5 days a week) or oral Deferasirox (daily) or combination of Deferoxamine and Deferiprone.
The dosage will depend on individual requirement, as determined by the treating hematologist.
干预措施: Standard Chelation (Drug)
Standard Chelation & Amlodipine
This arm will receive both chelation and amlodipine.
Amlodipine will be administered as a single daily dose. It will be administered at a dose of 0.1 mg/kg/day or maximum of 2.5 mg/day.
Standard Chelation therapy will be administered either by subcutaneous infusion of Deferoxamine (3-5 days a week) or oral Deferasirox (daily) or combination of Deferoxamine and Deferiprone.
The dosage will depend on individual requirement, as determined by the treating hematologist.
干预措施: Amlodipine (Drug)
Standard Chelation
Deferasirox or Deferoxamine or Deferiprone. Patients in this arm will be administered only standard chelation therapy,either by subcutaneous infusion of Chelation therapy of Deferoxamine (3-5 days a week) or oral Deferasirox (daily) or combination of Deferoxamine and Deferiprone.
The dosage will depend on individual requirement, as determined by the treating hematologist.
This will serve as the control arm of the study without any additional intervention.
干预措施: Standard Chelation (Drug)
结局指标
主要结局
Efficacy of amlodipine in retarding rate of myocardial iron deposition (Assessed by change in T2* times)
时间窗: At baseline, and then at 6 months and 12 months from the start of the study
Each patient will be randomized into either of two study arms: amlodipine plus chelation or chelation alone. All patients will undergo MRI and T2\* imaging at baseline and then at 6 and 12 month follow-up visits. Efficacy of Amlodipine will be assessed using change in T2\* times.
次要结局
- Effect of amlodipine therapy on left ventricular size, systolic and diastolic function(At baseline and then at 6 months and 12 months from the start of the study)
- Efficacy of amlodipine in retarding liver iron content (mg/g)(At baseline and then at 6 months and 12 months from the start of the study)
- Adverse effects of amlodipine therapy(At baseline and at 6 months and 12 months from the start of the study; at all visits to the Clinical Trial Unit pharmacy at the Aga Khan Hosptal for dispensing amlodipine and at all routine visits to the outpatient hematology clinic)
研究者
Dr Babar S Hasan
Assistant Professor
Aga Khan University