Efficacy of empagliflozin in prevention of Doxorubicin-induced cardiotoxicity in patients with breast cancer and receiving AC regimen (Cyclophosphamide + Doxorubicin): a randomized, placebo-controlled, double-blind trial
Evaluation of the effectiveness of Empagliflozin in preventing doxorubicin-induced cardiac toxicity in patients with breast cancer receiving AC regimen
Design
The clinical trial has a control group with parallel groups that is performed in two blind, randomized, phase 3 and on 64 patients. Block randomization method is used for randomization
Settings and conduct
This study was performed at the Imam Khomeini Hospital Cancer Institute, Tehran University of Medical Sciences, with the aim of investigating the possibility of prescribing Empagliflozin to prevent the occurrence of doxorubicin-induced cardiac toxicity in breast cancer patients and on 64 patients who are in two groups. Patients in the two groups are compared in terms of criteria including: blood levels of cardiac biomarkers and echocardiographic results.
Participants/Inclusion and exclusion criteria
Inclusion criteria: People who have recently been definitively diagnosed with breast cancer and are candidates for a chemotherapy regimen containing doxorubicin.
Intervention groups
Patients are divided into two groups. In the first group, Empagliflozin is prescribed with a chemotherapy regimen and in the second group, the same chemotherapy regimen is prescribed with a Placebo
Main outcome variables
Echocardiographic variables including: EF and GLS
Cardiac biomarkers including Troponin I, CK-MB and NT-proBNP
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20231014059713N1
Registration date:2023-11-18, 1402/08/27
Registration timing:prospective
Last update:2023-11-18, 1402/08/27
Update count:1
Registration date
2023-11-18, 1402/08/27
Registrant information
Name
Ehsan Shabani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 4424 3529
Email address
eshabani@razi.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-11-22, 1402/09/01
Expected recruitment end date
2024-09-21, 1403/06/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Efficacy of empagliflozin in prevention of Doxorubicin-induced cardiotoxicity in patients with breast cancer and receiving AC regimen (Cyclophosphamide + Doxorubicin): a randomized, placebo-controlled, double-blind trial
Public title
Efficacy of empagliflozin in prevention of Doxorubicin-induced cardiotoxicity in patients with breast cancer
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
A known case of breast cancer and candidate for receiving AC regimen
Signing a written informed consent to participate in the study
Patient age ≥ 18
Ability to take oral medicine
ECOG performance status less than or equal to 2
Exclusion criteria:
A history of breast cancer or a history of receiving chemotherapy regimen containing anthracycline or other chemotherapy drugs causing cardiomyopathy before entering the study
Inability to assess left ventricular (LV) function
Previous history of chest radiation therapy
Evidence of heart failure or left ventricular dysfunction based on echocardiography
Diagnosis or history of cardiomyopathies
Significant coronary artery disease (history of coronary stenting or stenosis based on previous angiography, history of known IHD or MI)
Severe valvular heart disease
Cardiac arrhythmia such as atrial fibrillation
Symptomatic hypotension or blood pressure less than 90 mmHg at the first visit
Liver enzymes more than 3 times ULN before entering the study
Significant renal failure (GFR less than 20 ml/min/1.73m2 with CKD-EPI formula) or need for dialysis
Simultaneous use of other drugs that can affect parameters of the study (such as ACEi, ARB, beta blockers)
Diabetes
Pregnancy
Breastfeeding
Hypersensitivity to SGLT2 inhibitor drugs
History of treatment with SGLT2 inhibitors during the last 3 months before the start of the study
Participation in other clinical studies simultaneously
Age
From 18 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Investigator
Outcome assessor
Sample size
Target sample size:
64
Randomization (investigator's opinion)
Randomized
Randomization description
Patients are randomly assigned to two groups of intervention (receiving chemotherapy regimen + empagliflozin) and control (receiving chemotherapy regimen + placebo) by using block randomization. This is a double-blinded trial {the patient, researcher (student) and the doctors} and the randomization will be performed by the project executor based on double or quadruple random tables and on each box, a number will be registered, the contents of which will be unknown, and will be given to the researcher and then to the patient.
Blinding (investigator's opinion)
Double blinded
Blinding description
Participants in the study, the physician who introduced them to the research team, the cardiologist who is responsible for measuring echocardiographic parameters of patients in both groups, and the laboratory staff who are responsible for measuring cardiac biomarkers in patients and the student who makes the arrangements (as a researcher) are blinded in this study. The project executor by using block randomization method (using two or four tables), assign a number randomly to each box containing the medicine or placebo, that is given to the researcher and the patient.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
The Institute of Pharmaceutical Sciences (TIPS) of the Tehran University of Medical Sciences
Street address
Poursina Avenue, Tehran University of Medical Sciences, Faculty of Pharmacy, The Institute of Pharmaceutical Sciences (TIPS), PO Box. 14176-13151, Iran
City
Tehran
Province
Tehran
Postal code
14176-13151
Approval date
2023-11-11, 1402/08/20
Ethics committee reference number
IR.TUMS.TIPS.REC.1402.102
Health conditions studied
1
Description of health condition studied
Breast cancer
ICD-10 code
C50
ICD-10 code description
Malignant neoplasm of breast
2
Description of health condition studied
Drug-induced cardiomyopathy
ICD-10 code
I42.7
ICD-10 code description
Cardiomyopathy due to drug and external agent
Primary outcomes
1
Description
LVEF (Left ventricular ejection fraction) : The left ventricular drain fraction or the amount of blood pumped from the left ventricle with each contraction.
Timepoint
Once at the beginning and once a week after the last chemotherapy session
Method of measurement
Using echocardiography performed by a cardiologist
2
Description
GLS (Global longitudinal strain): A sensitive criterion used by echocardiography to measure myocardial deformity and left ventricular contractile strength and can aid in the early diagnosis of cardiotoxicity. A decrease of more than 15% compared to the beginning or an absolute value of -19% after the start of anthracyclines is associated with a significant increase in the risk of future LVEF reduction.
Timepoint
At the beginning and one week after the last chemotherapy session
Method of measurement
Echocardiography by a cardiologist
Secondary outcomes
1
Description
Troponin I: One of the three types of troponin present in the body that is more specific to the myocardium of the heart and as a marker of the heart, can help diagnose myocardial damage. This enzyme increases within a few hours after heart damage and can last for a long time. Remain in my head for 10-14 days.
Timepoint
Once at the beginning and twice at one week after the second and last session of chemotherapy
Method of measurement
Blood sampling and blood level measurement by laboratory
2
Description
CK-MB: Creatine kinase and its MB isoenzyme are among the serological tests used to diagnose heart damage. This biomarker rises within the first 4 to 6 hours after heart injury and returns to baseline after 36 to 48 hours.
Timepoint
Once at the beginning and twice at one week after the second and last session of chemotherapy.
Method of measurement
Blood sampling and blood level measurement by laboratory
3
Description
NT-proBNP: It is one of the types of natriuretic peptides that indicates the filling pressure inside the heart and the stress of the walls of the ventricles, which is used to diagnose heart failure.
Timepoint
Once at the beginning and twice at one week after the second and last session of chemotherapy.
Method of measurement
Blood sampling and blood level measurement by laboratory
Intervention groups
1
Description
Intervention group: A group in which patients receive Empagliflozin drug produced by Actoverco at a dose of 10 mg once in the day along with chemotherapy. The patient will receive this drug from the first day of chemotherapy until one week after the last session. The duration of medication will be 49 or 70 days, depending on the patient's chemotherapy regimen.
Category
Prevention
2
Description
Control group: A group in which patients receive Placebo produced by Actoverco once in the day along with chemotherapy. The patient will receive placebo from the first day of chemotherapy until one week after the last session. The duration of medication will be 49 or 70 days, depending on the patient's chemotherapy regimen.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital Cancer Institute
Full name of responsible person
Ehsan Shabani
Street address
Dr. Gharib Street, the end of Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 2690
Email
ehsaneshabani1374.es@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
دکتر اکبر فتوحی
Street address
sixth floor, University Central Organization, corner of Quds Street, Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 8163 3685
Email
vcr@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
It is not necessary
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
Not applicable
Title and more details about the data/document
Final proposal report
When the data will become available and for how long
One year
To whom data/document is available
Researchers
Under which criteria data/document could be used
For other researchers to use the results of the data
From where data/document is obtainable
To the main executor of the project
Dr. Ehsan Shabani
Email: eshabani@razi.tums.ac.ir
Mobile: 09014462400
Address: No. 1, Nahid Ave., Marzdaran Blvd., Ashrafi Esfahani Expy
What processes are involved for a request to access data/document
Send email to the main executor of the project
Email: eshabani@razi.tums.ac.ir