Condition category
Cancer
Date applied
08/06/2016
Date assigned
04/07/2016
Last edited
04/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Cardiotoxicity refers to a health condition where the heart muscle is damaged electrical activities of the heart (which affects the beating of the heart and heart rate) is affected. Chemotherapy treatment is one of the causes of cardiotoxicity. Chemotherapy-induced cardiotoxicity (AIC) is a major cause of death and disease in cancer survivors. Anthracyclines are the drugs mostly responsible for the condition. Compared with other more common frequent forms of cardiomyopathy (chronic disease of the heart muscle) , AIC has an especially poor prognosis. It does not respond well to treatment and some 60% of people with AIC die within two years. There is evidence to suggest that oxidative stress has an important role in the development and progression of AIC. Oxidative stress happens when there are too many free radicals in the body. Free radicals are known to cause damage in body cells. The aim of the study is to look at the potential benefit of docosahexanoic acid (DHA) in addition to carvedilol (a beta blocker) to reduce the heart damage due to anthracycline chemotherapy in patients with breast cancer.

Who can participate?
Women aged between 18-75 with breast cancer and who are about to undergo anthracycline chemotherapy for the first time.

What does the study involve?
The participants are randomly allocated to one of two groups. into one of two groups. Those in the study group are treated with a high dose of DHA along with carvedilol for a few days before their chemotherapy begins. They are then treated with lower doses of these drugs during their chemotherapy treatment. The control group undergo chemotherapy treamtne as usual but are also given placebo (dummy) pills to represent the DHA and carvedilol. Biomarkers of oxidative stress are measured and MRI imaging taken before the study begins and after it ends. All patients are given a clinical follow up on days 10, 15, 30, 84, 180 with a final follow up at 12 months.

What are the possible benefits and risks of participating?
Possible benefits include the prevention of heart problems in the patients in the study group. All participants may benefit from having the clinical follow-up. Possible risks include minor and and reversible side effects related to the drugs included in the study like gastrointestinal discomfort (stomach ache) and bradycardia (slow heart rate).

Where is the study run from?
1. San Juan de Dios Hospital (Chile)
2. Del Salvador Hospital (Chile)

When is the study starting and how long is it expected to run for?
May 2016 to June 2019

Who is funding the study?
Scientific and Technological Development Fund (Chile)

Who is the main contact?
Dr Juan Guillermo Gormaz Araya
jgormaz@med.uchile.cl

Trial website

Contact information

Type

Scientific

Primary contact

Dr Juan Guillermo Gormaz Araya

ORCID ID

http://orcid.org/0000-0003-3424-4807

Contact details

Universidad de Chile
Independencia 1027
Independencia
Santiago
8380453
Chile
+56-2-29789539
jgormaz@med.uchile.cl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

11150999

Study information

Scientific title

Pharmacological preconditioning with docosahexanoic acid (DHA) plus carvedilol to prevent cardiotoxicity associated with anthracycline chemotherapy in patients with breast cancer

Acronym

CarDHA

Study hypothesis

Patients with breast cancer that receive DHA and carvedilol seven days before and three months after the first cycle of doxorubicin, will present at least 50% least cardiotoxicity-derived heart damage, than patients that receive the same chemotherapy with double placebo

Ethics approval

University of Chile Clinical Hospital, Faculty of Medicine of the University of Chile, 28/12/2015, ref: 208-2015

Study design

Randomized double-blind placebo-controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet. Contact information Karen Domínguez; mail: kyc.dominguez@gmail.com

Condition

Doxorubicin-induced cardiotoxicity

Intervention

The participants (female patients with breast cancer) are randomised into one of two groups:

1. The study group will be exposed for a short period to a high dose of DHA (1500 mg/day a few days before the beginning of the chemotherapy), and carvedilol (25 mg/day a few days before the beginning of the chemotherapy), and then treated with a low dose of these drugs for the next 3 months.
2. The control group will be exposed to double placebo in similar timings.

Biomarkers of oxidative stress will be measured and imaging taken pre and post intervention. All patients will have clinical follow up on the days 10, 15, 30, 84, 180 with a final follow up at 12 months.

Intervention type

Drug

Phase

Drug names

1. Docosahexanoic acid
2. Carvedilol

Primary outcome measures

1. Affected tissue and cardiac remodeling at six months, measured using cardiac magnetic resonance at baseline and 3 months after the end of chemotherapy
2. Change from baseline in global LVEF, measured using echocardiogram and cardiac magnetic resonance. Ecocardiogram is taken measure at baseline, 3 and 6 months after the end of chemotherapy, MRI at baseline and 3 months after the end of chemotherapy
3. Change from baseline in corrected QT Interval via electrocardiogram, at baseline, day 2, 4 and 3 months after the end of chemotherapy
4. Change from baseline in NT-ProBNP, via plasmatic levels, measured at baseline, day 2, 4 and 3 months after the end of chemotherapy

Secondary outcome measures

1. Lipid peroxidation (Malondialdehyde levels) at baseline, day 2, day 4 and 3 months after chemotherapy
2. Erythrocyte antioxidant enzymes activity (SOD, CAT, GSH-Px) at baseline, day 2, day 4 and 3 months after chemotherapy
3. Erythrocyte Tiol Index (GSH/GSSG), at baseline, day 2, day 4 and 3 months after chemotherapy
4. Ferric reducing ability of plasma (FRAP) at baseline, day 2, day 4 and 3 months after chemotherapy

Overall trial start date

30/05/2016

Overall trial end date

30/06/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Females aged between 18 and 75 years old
2. Breast Cancer Diagnosis
3. Entering first cycle of chemotherapy
4. Performance status of 0-2 in the Eastern Cooperative Oncology Group (ECOG) score.
5. Subject must be able and willing to sign an informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

32

Participant exclusion criteria

1. History of renal (serum creatinine greater than 2 mg / ml) or hepatic insufficiency (bilirubin> 3.0 mg / dl or serum albumin <3.5 g / dl or prothrombin time <60% in the absence of oral anticoagulant therapy or ultrasound signs of chronic liver damage)
2. History of heart failure
3. History of cardiac valvulopathy
4. Baseline LVEF <50% determined by transthoracic echocardiogram
5. Cardiogenic shock
6. Any serious medical co-morbidity that determine life expectancy < 6 months
7. Current participation in any other clinical investigation
8. Any condition that contraindicates chemotherapy (i.e. Pregnancy, Lactation)
9. History of severe adverse reaction to carvedilol
10. History of severe adverse reaction to DHA
11. Previous treatment with beta-blockers within the last 3 months
12. Use of Vitamin E, Vitamin C or probucol, during the last three months
13. Use of oral anticoagulants
14. History of coagulation disorders

Recruitment start date

30/05/2016

Recruitment end date

30/12/2018

Locations

Countries of recruitment

Chile

Trial participating centre

San Juan de Dios Hospital
Huérfanos 3255
Santiago
8350488
Chile

Trial participating centre

Del Salvador Hospital
Avenida Salvador 364, Providencia
Santiago
7500922
Chile

Sponsor information

Organisation

Scientific and Technological Development Fund (FONDECYT; Fondo de Desarrollo Científico y Tecnológico) (Chile)

Sponsor details

Moneda 1375
Santiago
8340486
Chile
+56-2-23654400
esilva@conicyt.cl

Sponsor type

Government

Website

http://www.conicyt.cl/fondecyt/

Funders

Funder type

Government

Funder name

Scientific and Technological Development Fund (FONDECYT Fondo de Desarrollo Científico y Tecnológico) (Chile)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes