Carvedilol Treatment in Patients with Transfusion-Dependent Thalassemia

ISRCTN	ISRCTN14221392
DOI	https://doi.org/10.1186/ISRCTN14221392
Protocol serial number	CTDT-2016
Sponsor	Thailand Research Fund
Funder	Thailand Research Fund

Submission date: 18/07/2018
Registration date: 24/07/2018
Last edited: 08/11/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

Contact information

Dr Suchaya Silvilairat
Scientific

Department of Pediatrics, Faculty of Medicine, Chiang Mai University
Chiang Mai
50200
Thailand

ORCID ID	0000-0001-7045-1817

Study information

Primary study design	Interventional
Study design	Interventional prospective single-centre single-arm non-randomised cohort study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Carvedilol improves left ventricular diastolic dysfunction in patients with Transfusion-Dependent Thalassemia
Study acronym	CTDT
Study objectives	Carvedilol can attenuate LV diastolic dysfunction due to iron overload in patients with transfusion-dependent thalassemia who had ventricular dysfunction.
Ethics approval(s)	Research Ethics Committee 2, Faculty of Medicine, Chiang Mai University, 23/01/2012, PED-11-863-FB
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Carvedilol
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	01/12/2017

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	All
Target sample size at registration	15
Key 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
Key exclusion criteria	N/A
Date of first enrolment	01/01/2014
Date of final enrolment	31/12/2016

Locations

Countries of recruitment

Thailand

Study participating centre

Chiang Mai University

110 Tambon. Sripoom
Inthawaroroj Road
A.Muang
Chiang Mai
50200
Thailand

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	Only the final conclusion of analysis of the results of the study will be available upon request from asilvilairat@gmail.com.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

08/11/2019: Internal review.