Amlodipine for Myocardial Iron in Thalassemia (AMIT)

Aga Khan University

Status and phase: Completed; Phase 3; Phase 2

Conditions: Thalassemia

Treatments: Drug: Amlodipine; Drug: Standard Chelation

Study type: Interventional

Funder types: Other

Identifiers

NCT02065492

AMIT

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 6 to 20 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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20 participants in 2 patient groups

Standard Chelation & Amlodipine

Experimental group

Description:

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.

Treatment:

Drug: Standard Chelation

Drug: Amlodipine

Standard Chelation

Active Comparator group

Description:

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.

Treatment:

Drug: Standard Chelation