Condition category
Circulatory System
Date applied
18/07/2018
Date assigned
24/07/2018
Last edited
24/07/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

https://www.trf.or.th

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

Publication citations

Additional files

Editorial Notes