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

The Use of the Calcium Channel Blocker Amlodipine as an Adjuvant Treatment to Iron Chelation for the Prevention of Iron Overload Cardiomyopathy in Patients With Thalassemia

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.

Study Overview

• Status: Unknown
• Conditions: Iron Overload; Beta-Thalassemia
• Intervention / Treatment: Drug: Deferasirox; Drug: Amlodipine

Detailed Description

Selection of Study Population: The study will enroll 60 adult subjects with transfusion dependent thalassemia receiving deferasirox iron chelation therapy. All eligible subjects will be asked to provide informed consent before participating in the study.

Randomization: Subjects will be randomized in a 1:1 ratio to either continuation of their DFX (control arm) or a combination of DFX plus amlodipine (amlodipine arm).

Treatment: Subjects randomized to the amlodipine arm will receive open label medication (amlodipine) starting at 2.5mg/day and up-titrated by 2.5mg every 7-14 days with the goal of reaching 10mg/day. DFX dose in either arm will not be adjusted unless it was deemed unsafe to remain on the same dose of DFX by the treating physician (significant side effects, lack of efficacy or over-chelation) or T2* drops below 8 ms.

Safety Assessment: Weekly or fortnightly amlodipine titration will be conducted by the research physician in-clinic, based on blood pressure, tolerability, and presence or absence of side-effects.

Adverse Events will be assessed at every visit after the first dose through to the last subject visit.

Efficacy Assessment: the efficacy of amlodipine combined to standard chelation therapy will be assessed by cardiac T2*MRI, done at baseline and 12 months post treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rebecca Leroux, RN, CCRP; Phone Number: +1-416-715-6485; Email: rebecca.leroux@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • University Health Network
      • Contact: Rebecca Leroux, RN, CCRP; Phone Number: +1-416-715-6485; Email: rebecca.leroux@uhn.ca
      • Principal Investigator: Kevin Kuo, MD, MSc, FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Deferasirox; deferasirox iron chelation therapy and standard of care by the treating physician	Drug: Deferasirox; Deferasirox administered per standard of care by the treating physician
Experimental: Deferasirox plus amlodipine; deferasirox iron chelation therapy with amlodipine	Drug: Deferasirox; Deferasirox administered per standard of care by the treating physician; Drug: Amlodipine; amlodipine titrated up to 10 mg daily or maximum tolerated dose, whichever comes first

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cardiac T2*	Change in cardiac T2* as determined by MRI	12 months following randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular ejection fraction	Change in left ventricular ejection fraction (in %) as determined by MRI	12 months following randomization
Number of Participants with Adverse Events		12 months following randomization

Collaborators and Investigators

• Sponsor: Kevin H.M. Kuo, MD, MSc, FRCPC
• Investigators: Principal Investigator: Kevin HM Kuo, MD MSc FRCPC, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 12, 2015
• First Posted (Estimate): June 17, 2015

Study Record Updates

• Last Update Posted (Estimate): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Iron Overload; Thalassemia; beta-Thalassemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Amlodipine; Deferasirox
• Other Study ID Numbers: CANALI