Amlodipine as Adjuvant Treatment to Iron Chelation for Prevention of Cardiac Iron Overload in Thalassemia Patients

NCT02474420 | Unknown DMC

• 1 other identifier: CANALI
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open label, two arms superiority trial of a representative population of patients with a primary diagnosis of transfusion dependent thalassemia with evidence of moderate cardiac iron overload, defined as an average T2\* MRI parameter at the mid inter-ventricular septum between 10 and 20ms.

Conditions

Beta-Thalassemia; Iron Overload

Outcome Measures

Primary Outcomes (1)

• Change in cardiac T2*

  Change in cardiac T2\* as determined by MRI

  12 months following randomization

Secondary Outcomes (2)

• Change in left ventricular ejection fraction

  12 months following randomization

• Number of Participants with Adverse Events

  12 months following randomization

Study Arms (2)

Deferasirox

ACTIVE COMPARATOR

deferasirox iron chelation therapy and standard of care by the treating physician

Drug: Deferasirox

Deferasirox plus amlodipine

EXPERIMENTAL

deferasirox iron chelation therapy with amlodipine

Drug: Amlodipine; Drug: Deferasirox

Interventions

Amlodipine DRUG

amlodipine titrated up to 10 mg daily or maximum tolerated dose, whichever comes first

Deferasirox plus amlodipine

Deferasirox DRUG

Deferasirox administered per standard of care by the treating physician

Deferasirox; Deferasirox plus amlodipine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of transfusion-dependent Thalassemia being followed by a thalassemia comprehensive care clinic Age 18 or older
• Taking deferasirox and on a stable dose for \>3 months
• Evidence on cardiac MRI of mild to moderate cardiac iron overload (T2\*\<20ms but ≥10ms) as measured within 3 months prior to randomization. If a recent cardiac MRI has not been obtained, patients who otherwise meet all eligibility criteria and provide appropriate consent will undergo a cardiac MRI to confirm eligibility
• Preserved left ventricular ejection fraction (LVEF) \>55% as measured by cardiac MRI. If a recent cardiac MRI has not been obtained, patients who otherwise meet all eligibility criteria and provide appropriate consent will undergo a cardiac MRI to confirm eligibility.
• Agreeable to use an approved method of contraception if female of childbearing potential for the entire duration of the study.

You may not qualify if:

• Serum ferritin \< 500 ng/mL at screening
• Liver iron concentration \> 30 mg/g dw as measured by liver R2 MRI (FerriScan)
• Congestive heart failure
• Severe refractory Hypotension (less than 90 mmHg systolic)
• Currently taking any calcium channel blockers
• Pregnancy or nursing (a negative HCG (pregnancy) test must be obtained prior to randomization)
• As a result of medical review, physical examination or screening investigations, the Principal Investigator (PI) considers the subject unfit for the study
• No fixed address
• Hypersensitivity to amlodipine or other dihydropyridines

Sponsors & Collaborators

• Kevin H.M. Kuo, MD, MSc, FRCPC: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Related Publications (1)

• 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

MeSH Terms

Conditions

beta-Thalassemia; Iron Overload

Interventions

Amlodipine; Deferasirox

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles

Study Officials

• Kevin HM Kuo, MD MSc FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Leroux, RN, CCRP

CONTACT

+1-416-715-6485; rebecca.leroux@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 17, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2018
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

CA (1)