Amlodipine for Myocardial Iron in Thalassemia

NCT ID: NCT02065492

Last Updated: 2017-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2015-11-30

Brief Summary

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.

Detailed 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.

Conditions

Thalassemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Standard Chelation

Intervention Type: DRUG

This will comprise of standard chelation drugs (Deferasirox or Deferoxamine or Combination of Deferoxamine and Deferiprone).The dosage and drug used will depend on ferritin levels and individual requirement, as determined by the treating hematologist and will be in accordance with the Iron chelation guidelines from Pakistan Thalassemia Society.

Amlodipine

Intervention Type: DRUG

doses of 0.2 to 0.25 mg/kg/day PO would be given during this trial

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.

Group Type: ACTIVE_COMPARATOR

Standard Chelation

Intervention Type: DRUG

This will comprise of standard chelation drugs (Deferasirox or Deferoxamine or Combination of Deferoxamine and Deferiprone).The dosage and drug used will depend on ferritin levels and individual requirement, as determined by the treating hematologist and will be in accordance with the Iron chelation guidelines from Pakistan Thalassemia Society.

Interventions

Standard Chelation

This will comprise of standard chelation drugs (Deferasirox or Deferoxamine or Combination of Deferoxamine and Deferiprone).The dosage and drug used will depend on ferritin levels and individual requirement, as determined by the treating hematologist and will be in accordance with the Iron chelation guidelines from Pakistan Thalassemia Society.

Intervention Type: DRUG

Amlodipine

doses of 0.2 to 0.25 mg/kg/day PO would be given during this trial

Intervention Type: DRUG

Other Intervention Names

Asunra or Kelfer or Desferal; L-type calcium channel blocker

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aga Khan University

OTHER

Sponsor Role: lead

Responsible Party

Dr Babar S Hasan

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Babar Hasan

Role: PRINCIPAL_INVESTIGATOR

Aga Khan University

Locations

Aga Khan University Hospital

Karachi, Sindh, Pakistan

Countries

Pakistan

References

Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.

Reference Type: DERIVED

PMID: 37975597 (View on PubMed)

Shakoor A, Zahoor M, Sadaf A, Alvi N, Fadoo Z, Rizvi A, Quadri F, Tipoo FA, Khurshid M, Sajjad Z, Colan S, Hasan BS. Effect of L-type calcium channel blocker (amlodipine) on myocardial iron deposition in patients with thalassaemia with moderate-to-severe myocardial iron deposition: protocol for a randomised, controlled trial. BMJ Open. 2014 Dec 8;4(12):e005360. doi: 10.1136/bmjopen-2014-005360.

Reference Type: DERIVED

PMID: 25492271 (View on PubMed)

Other Identifiers

AMIT

Identifier Type: -

Identifier Source: org_study_id