Amlodipine for Myocardial Iron in Thalassemia

NCT02065492 | Completed Phase 2

• 1 other identifier: AMIT
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Thalassemia

Keywords

Thalassemia; Amlodipine; Chelation; T2*; MRI; Myocardial Iron

Outcome Measures

Primary Outcomes (1)

• Efficacy of amlodipine in retarding rate of myocardial iron deposition (Assessed by change in T2* times)

  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.

  At baseline, and then at 6 months and 12 months from the start of the study

Secondary Outcomes (3)

• 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

Study Arms (2)

Standard Chelation & Amlodipine

EXPERIMENTAL

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.

Drug: Standard Chelation; Drug: Amlodipine

Standard Chelation

ACTIVE COMPARATOR

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.

Drug: Standard Chelation

Interventions

Standard Chelation 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.

Also known as: Asunra or Kelfer or Desferal

Standard Chelation; Standard Chelation & Amlodipine

Amlodipine DRUG

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

Also known as: L-type calcium channel blocker

Standard Chelation & Amlodipine

Eligibility Criteria

• Age: 6 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aga Khan University: lead

Study Sites (1)

Aga Khan University Hospital

Karachi, Sindh, 74800, Pakistan

Location

Related Publications (2)

• 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.

  PMID: 37975597 DERIVED

• 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.

  PMID: 25492271 DERIVED

MeSH Terms

Conditions

Thalassemia

Interventions

Deferoxamine; Amlodipine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Babar Hasan

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 17, 2014
• First Posted: February 19, 2014
• Study Start: February 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: June 29, 2017

Record last verified: 2017-06

Locations

PA (1)