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

Primary Purpose

Beta-Thalassemia, Iron Overload

Status

Unknown status

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Amlodipine

Deferasirox

About this trial

This is an interventional treatment trial for Beta-Thalassemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Health NetworkRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Deferasirox

Deferasirox plus amlodipine

Arm Description

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

deferasirox iron chelation therapy with amlodipine

Outcomes

Primary Outcome Measures

Change in cardiac T2*

Change in cardiac T2* as determined by MRI

Secondary Outcome Measures

Change in left ventricular ejection fraction

Change in left ventricular ejection fraction (in %) as determined by MRI

Number of Participants with Adverse Events

Full Information

NCT ID

NCT02474420

First Posted

June 11, 2015

Last Updated

October 24, 2016

Sponsor

Kevin H.M. Kuo, MD, MSc, FRCPC

1. Study Identification

Unique Protocol Identification Number

NCT02474420

Brief Title

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

Acronym

CANALI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Unknown status

Study Start Date

June 2015 (undefined)

Primary Completion Date

June 2017 (Anticipated)

Study Completion Date

June 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Kevin H.M. Kuo, MD, MSc, FRCPC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Beta-Thalassemia, Iron Overload

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Deferasirox

Arm Type

Active Comparator

Arm Description

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

Arm Title

Deferasirox plus amlodipine

Arm Type

Experimental

Arm Description

deferasirox iron chelation therapy with amlodipine

Intervention Type

Drug

Intervention Name(s)

Amlodipine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Deferasirox

Intervention Description

Deferasirox administered per standard of care by the treating physician

Primary Outcome Measure Information:

Title

Change in cardiac T2*

Description

Change in cardiac T2* as determined by MRI

Time Frame

12 months following randomization

Secondary Outcome Measure Information:

Title

Change in left ventricular ejection fraction

Description

Change in left ventricular ejection fraction (in %) as determined by MRI

Time Frame

12 months following randomization

Title

Number of Participants with Adverse Events

Time Frame

12 months following randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rebecca Leroux, RN, CCRP

Phone

+1-416-715-6485

rebecca.leroux@uhn.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kevin HM Kuo, MD MSc FRCPC

Organizational Affiliation

University Health Network, Toronto

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Health Network

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2C4

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rebecca Leroux, RN, CCRP

Phone

+1-416-715-6485

rebecca.leroux@uhn.ca

First Name & Middle Initial & Last Name & Degree

Kevin Kuo, MD, MSc, FRCPC

12. IPD Sharing Statement

Learn more about this trial

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

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