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

• Published in: BMJ open 2014-01, Vol.4 (12), p.e005360-e005360
• Main Authors: Shakoor, Amarah, Zahoor, Maaman, Sadaf, Alina, Alvi, Najveen, Fadoo, Zehra, Rizvi, Arjumand, Quadri, Farheen, Tipoo, Fateh Ali, Khurshid, Mohammad, Sajjad, Zaffar, Colan, Steven, Hasan, Babar S
• Format: Article
• Language: English
• Subjects: Adolescent; Amlodipine - administration & dosage; Blood diseases; Calcium Channel Blockers - administration & dosage; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - metabolism; Cardiac function; Cardiomyopathies - drug therapy; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathy; Cardiovascular disease; Chelating Agents - administration & dosage; Chelation therapy; Child; Congenital diseases; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Heart - drug effects; Heart - physiopathology; Heart failure; Humans; Hypertension; Hypotheses; Iron; Iron - metabolism; Iron Overload - complications; Iron Overload - drug therapy; Iron Overload - metabolism; Magnetic Resonance Imaging, Cine; Male; Myocardium - metabolism; Myocardium - pathology; Oxidative stress; Paediatrics; Prospective Studies; Severity of Illness Index; Stroke Volume; Thalassemia - complications; Thalassemia - drug therapy; Thalassemia - metabolism; Time Factors; Treatment Outcome; Young Adult
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2014-005360

Introduction Sideroblastic cardiomyopathy secondary to repeated blood transfusions is a feared complication in thalassaemia. Control of myocardial iron is thus becoming the cornerstone of thalassaemia management. Recent evidence suggests a role for L-type Ca2+ channels in mediating iron uptake by the heart. Blocking the cellular iron uptake through these channels may add to the benefit of therapy to standard chelation in reducing myocardial iron. We aim to determine the efficacy of amlodipine (a calcium channel blocker) as an adjunct to standard aggressive chelation in retarding myocardial iron deposition in thalassaemics with or without cardiomyopathy. Outcomes The primary outcome is to compare the efficacy of amlodipine+chelation (intervention) versus standard chelation (control) in retarding myocardial iron deposition. Secondary outcomes include the effect of amlodipine therapy on systolic and diastolic function, strain and strain rate and liver iron content. Methods and analysis This is a single-centre, parallel-group, prospective randomised control trial. Twenty patients will be randomised in a 1:1 allocation ratio into the intervention and control arms. In addition to conventional echocardiography, MRI T2* values for assessment of cardiac and liver iron load will be obtained at baseline and at 6 and 12 months. Cardiac T2* will be reported as the geometric mean and per cent coefficient of variation, and an increase in cardiac T2* values from baseline will be used as an end point to compare the efficacy of therapy. A p Value of