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

• ClinicalTrials.gov Identifier: NCT02474420
• Recruitment Status: Unknown
• First Posted: June 17, 2015
• Last Update Posted: October 26, 2016
• Sponsor: Kevin H.M. Kuo, MD, MSc, FRCPC
• Information provided by (Responsible Party): Kevin H.M. Kuo, MD, MSc, FRCPC, University Health Network, Toronto

Tracking Information

• First Submitted Date: June 11, 2015
• First Posted Date: June 17, 2015
• Last Update Posted Date: October 26, 2016
• Study Start Date: June 2015
• Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2015)

Change in cardiac T2* [ Time Frame: 12 months following randomization ]

Change in cardiac T2* as determined by MRI

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 12, 2015)

• Change in left ventricular ejection fraction [ Time Frame: 12 months following randomization ]
  Change in left ventricular ejection fraction (in %) as determined by MRI
• Number of Participants with Adverse Events [ Time Frame: 12 months following randomization ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Amlodipine as Adjuvant Treatment to Iron Chelation for Prevention of Cardiac Iron Overload in Thalassemia Patients
• 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Beta-Thalassemia
• Iron Overload

Intervention

• Drug: Amlodipine
  amlodipine titrated up to 10 mg daily or maximum tolerated dose, whichever comes first
• Drug: Deferasirox
  Deferasirox administered per standard of care by the treating physician

Study Arms

• Active Comparator: Deferasirox
  deferasirox iron chelation therapy and standard of care by the treating physician
  Intervention: Drug: Deferasirox
• Experimental: Deferasirox plus amlodipine
  deferasirox iron chelation therapy with amlodipine
  Interventions:

  • Drug: Amlodipine
  • Drug: Deferasirox

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: June 12, 2015): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2018
• Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02474420
• Other Study ID Numbers: CANALI
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kevin H.M. Kuo, MD, MSc, FRCPC, University Health Network, Toronto
• Original Responsible Party: Same as current
• Current Study Sponsor: Kevin H.M. Kuo, MD, MSc, FRCPC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kevin HM Kuo, MD MSc FRCPC; University Health Network, Toronto

• PRS Account: University Health Network, Toronto
• Verification Date: October 2016