Plain English Summary
Background and study aims
Thalassemia is a blood disorder that causes the body to make an abnormal form of hemoglobin, a protein that carries oxygen in the blood. Severe thalassemia can lead to hemolysis (bursting of red blood cells) and ineffective production of red blood cells. This can lead to symptoms such as anemia, jaundice, swelling of the liver and spleen, changes to the skeleton and delayed growth. For patients with such symptoms, the main treatment is regular blood transfusion and removal of excess iron from the body (iron chelation therapy).
Transfusion-dependent thalassemia is a form of thalassemia that relies on this treatment. Iron chelation therapy is also essential for patients with this, as the most common cause of death in patients with transfusion-dependent thalassemia is iron overload cardiomyopathy, where iron deposits in the heart and leads to heart dysfunction (ventricular dysfunction). Therefore, iron chelation therapy is required to remove this iron from the heart.
Carvedilol is a drug used to treat ventricular dysfunction after a heart attack. The aim of this study was to determine whether carvedilol is an effective treatment for transfusion-dependent thalassemia patients with heart dysfunction.
Who can participate?
Patients with transfusion-dependent thalassemia who have heart dysfunction
What does the study involve?
All patients will be given carvedilol to take daily for 6 months, and will have their heart function assessed before taking the drug and 3 and 6 months after.
What are the possible benefits and risks of participating?
The possible benefit to participants is that taking carvedilol may improve their heart function. The possible risks of participating are side effects of the drug, such as bradycardia and hypotension.
Where is the study run from?
Department of Pediatrics, Faculty of Medicine, Chiang Mai, Thailand
When does the study start and how long is it expected to run for?
October 2011 to December 2017
Who is funding the study?
Thai Research Fund (Thailand)
Who is the main contact?
Dr Suchaya Silvilairat
asilvilairat@gmail.com
Trial website
Contact information
Type
Scientific
Primary contact
Dr Suchaya Silvilairat
ORCID ID
http://orcid.org/0000-0001-7045-1817
Contact details
Department of Pediatrics
Faculty of Medicine
Chiang Mai University
Chiang Mai
50200
Thailand
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CTDT-2016
Study information
Scientific title
Carvedilol improves left ventricular diastolic dysfunction in patients with Transfusion-Dependent Thalassemia
Acronym
CTDT
Study hypothesis
Carvedilol can attenuate LV diastolic dysfunction due to iron overload in patients with transfusion-dependent thalassemia who had ventricular dysfunction.
Ethics approval
Research Ethics Committee 2, Faculty of Medicine, Chiang Mai University, 23/01/2012, PED-11-863-FB
Study design
Interventional prospective single-centre single-arm non-randomised cohort study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
Transfusion-dependent thalassemia with ventricular diastolic dysfunction
Intervention
All patients were initially given carvedilol in doses of 0.1 mg/kg/day, the medication being divided into 2 separate doses. The dosage was doubled every two weeks until the target dose of 0.8 mg/kg/day was reached and continued for 6 months. The maximum dose was 50 mg/day. All patients had their cardiac function assessed by echocardiography at 3 and 6 months and the level of iron in the heart was also evaluated at 3 and 6 months using cardiac magnetic resonance imaging (MRI). Side effects of the drug were monitored though the study.
Intervention type
Drug
Phase
Not Specified
Drug names
Carvedilol
Primary outcome measure
Left ventricular diastolic function, measured by echocardiography at the baseline and 3 and 6 months after treatment. Echocardiographic data included pulse wave Doppler assessment of mitral and pulmonary venous flows (ventricular diastolic filling analysis) and tissue Doppler imaging. Diastolic left ventricular dysfunction was graded according to pulse wave Doppler of mitral and pulmonary venous flows and tissue Doppler imaging.
Secondary outcome measures
Side effects of carvedilol use, assessed at the baseline and 3 and 6 months after treatment:
1. Blood pressure
2. Heart rate
3. Symptoms such as dizziness, chest pain and swelling
Overall trial start date
01/10/2011
Overall trial end date
01/12/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Severe forms of homozygous beta-thalassemia and beta-thalassemia/hemoglobin E disease
2. Transfusion-dependent thalassemia
3. Aged 8-25 years
4. Left ventricular diastolic dysfunction
Participant type
Patient
Age group
Other
Gender
Both
Target number of participants
15
Participant exclusion criteria
N/A
Recruitment start date
01/01/2014
Recruitment end date
31/12/2016
Locations
Countries of recruitment
Thailand
Trial participating centre
Chiang Mai University
110 Tambon. Sripoom
Inthawaroroj Road
A.Muang
Chiang Mai
50200
Thailand
Sponsor information
Organisation
Thailand Research Fund
Sponsor details
14th Floor
SM Tower
979/17-21 Phaholyothin Road
Samsan Nai
Phyathai
Bangkok
10400
Thailand
6622788200
callcenter@trf.or.th
Sponsor type
Government
Website
Funders
Funder type
Not defined
Funder name
Thailand Research Fund
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD sharing statement:
Only the final conclusion of analysis of the results of the study will be available upon request from asilvilairat@gmail.com.
Intention to publish date
31/08/2018
Participant level data
Available on request
Basic results (scientific)
In TDT patients, Doppler parameters indicating LV diastolic dysfunction including atrial reversal flow velocity, atrial reversal flow duration, and PVAR-MVA duration were significantly decreased and the grades of LV diastolic dysfunction were improved since 3 months after the start of the carvedilol treatment. These findings indicate that carvedilol treatment effectively improved LV diastolic function in TDT patients, improvements being measurable 3 months after the onset of treatment.
LV diastolic function showed improvement in patients with TDT since 3 months of carvedilol treatment. Doppler parameters indicating LV diastolic dysfunction including atrial reversal flow velocity, atrial reversal flow duration, the difference of pulmonary vein atrial reversal duration and mitral valve A wave duration significantly decreased since 3 months of carvedilol treatment. These findings indicate that 3-month carvedilol treatment in the format described in this study leads to effective improvement in LV diastolic function in patients with TDT.
Publication list