Beta-ThalassemiaCANALINCT02474420
Amlodipine as Adjuvant Treatment to Iron Chelation for Prevention of Cardiac Iron Overload in Thalassemia Patients
A study testing Amlodipine and Deferasirox in people with Beta-Thalassemia and Iron Overload, run by Kevin H.M. Kuo, MD, MSc, FRCPC at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Beta-Thalassemia, Iron Overload
- What is being tested?
- Amlodipine and Deferasirox
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2015to Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
University Health Network
Toronto, Ontario, M5G 2C4
Rebecca Leroux, RN, CCRP, +1-416-715-6485, rebecca.leroux@uhn.ca
Kevin Kuo, MD, MSc, FRCPC
About this study
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
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.
Read the 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.
- Conditions
- Beta-Thalassemia, Iron Overload
- Being tested
- Amlodipine, Deferasirox
- Medical subject headings
- beta-Thalassemia, Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmlodipineDrug
amlodipine titrated up to 10 mg daily or maximum tolerated dose, whichever comes first
DeferasiroxDrug
Deferasirox administered per standard of care by the treating physician
| Study group | Role | What they receive |
|---|---|---|
| Deferasirox | Active comparator | deferasirox iron chelation therapy and standard of care by the treating physician Receives: Drug: Deferasirox |
| Deferasirox plus amlodipine | Experimental | deferasirox iron chelation therapy with amlodipine Receives: Drug: Amlodipine; Drug: Deferasirox |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cardiac T2*
Change in cardiac T2* as determined by MRI
Measured: 12 months following randomization
Secondary outcomes (2)
Change in left ventricular ejection fraction
Change in left ventricular ejection fraction (in %) as determined by MRI
Measured: 12 months following randomization
Number of Participants with Adverse Events
Measured: 12 months following randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionJun 2017 (estimated)
- Study completionJun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Beta-ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kevin H.M. Kuo, MD, MSc, FRCPC
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kevin H.M. Kuo, MD, MSc, FRCPC, University Health Network, Toronto
- Investigators
- Kevin HM Kuo, MD MSc FRCPC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02474420
- Sponsor's protocol ID
- CANALI
- Acronym
- CANALI
- Status last verified
- Oct 2016
- First submitted
- 11 Jun 2015
- Last updated
- 26 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37975597
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02474420
- Acronym / sponsor ID
- CANALI / CANALI
- Conditions
- Beta-Thalassemia, Iron Overload
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Kevin H.M. Kuo, MD, MSc, FRCPCUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 17 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deferasirox | Active comparator | Drug: Deferasiroxdeferasirox iron chelation therapy and standard of care by the treating physician |
| Deferasirox plus amlodipine | Experimental | Drug: Amlodipine, Drug: Deferasiroxdeferasirox iron chelation therapy with amlodipine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amlodipineamlodipine titrated up to 10 mg daily or maximum tolerated dose, whichever comes first | Drug | Deferasirox plus amlodipine |
| DeferasiroxDeferasirox administered per standard of care by the treating physician | Drug | Deferasirox, Deferasirox plus amlodipine |
Primary outcome
Change in cardiac T2*
Time frame: 12 months following randomization
Change in cardiac T2* as determined by MRI
2 secondary outcomes
Change in left ventricular ejection fraction
Time frame: 12 months following randomization
Number of Participants with Adverse Events
Time frame: 12 months following randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
- Derived from this study: PubMed 37975597Padhani 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin HM Kuo, MD MSc FRCPC principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Amlodipine and Deferasirox in people with Beta-Thalassemia and Iron Overload, run by Kevin H.M. Kuo, MD, MSc, FRCPC at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rebecca Leroux, RN, CCRP (+1-416-715-6485, rebecca.leroux@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cardiac T2* (time frame: 12 months following randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02474420, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2016.