Comparison of the effect of sacubitril/valsartan with enalapril in the prevention of cardiotoxicity caused by the co-treatment of doxorubicin and trastuzumab in patients with breast cancer: a randomized and controlled clinical trial
Comparison of the effect of sacubitril/valsartan with enalapril in the prevention of cardiotoxicity caused by the co-treatment of doxorubicin and trastuzumab in patients with breast cancer
Design
In one group, patients will receive sacubitril/valsartan at a dose of 50 mg daily for three months. In the parallel group, patients will receive enalapril at a dose of 5 mg daily for three months.
Settings and conduct
Clinical trial - Isfahan University of Medical Sciences
Participants/Inclusion and exclusion criteria
Inclusion Criteria: Adult patients newly diagnosed with HER2-positive breast cancer who have not received any anthracycline-containing chemotherapy regimen in the past.
Exclusion Criteria: Patients with a systolic blood pressure less than 100 mmHg. Patients with contraindications for medications from the ACE inhibitor, ARB, and neprilysin inhibitor families. Patients who experience potential adverse effects or allergic reactions to sacubitril/valsartan or enalapril during treatment. Patients who develop another serious illness during the intervention and are required to receive various medications affecting the cardiovascular system.
Intervention groups
Based on which group the patient has been randomly assigned to, a dose of 50 mg daily of sacubitril/valsartan or 5 mg daily of enalapril will be prescribed for the patient for a minimum of three months.
Main outcome variables
Prevention of cardiac toxicity due to the combined treatment of doxorubicin and trastuzumab.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20180722040556N11
Registration date:2025-01-20, 1403/11/01
Registration timing:prospective
Last update:2025-01-20, 1403/11/01
Update count:0
Registration date
2025-01-20, 1403/11/01
Registrant information
Name
Azadeh Moghaddas
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 31 1792 7074
Email address
moghaddas@pharm.mui.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2025-02-18, 1403/11/30
Expected recruitment end date
2026-03-20, 1404/12/29
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of the effect of sacubitril/valsartan with enalapril in the prevention of cardiotoxicity caused by the co-treatment of doxorubicin and trastuzumab in patients with breast cancer: a randomized and controlled clinical trial
Public title
Comparison of the effect of sacubitril/valsartan with enalapril in the prevention of cardiotoxicity caused by the co-treatment of doxorubicin and trastuzumab in patients with breast cancer: a randomized and controlled clinical trial
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Adult patients newly diagnosed with HER2-positive breast cancer who have not received any anthracycline-containing chemotherapy regimen in the past.
These patients are to be treated with an AC regimen containing 60 mg/m² of doxorubicin and 600 mg/m² of cyclophosphamide for 4-6 cycles, followed by treatment with trastuzumab.
Patients are expected to receive at least three cycles of trastuzumab (typically 6 mg/kg every three weeks) alone or in combination with or after a taxane-containing regimen if necessary, following the doxorubicin regimen.
Study participants must have a baseline left ventricular ejection fraction (EF) of at least 50% (≥50%).
They should have no history of cardiovascular diseases such as heart failure, angina, or hypertension.
The patient must provide consent to participate in the study and cooperate with the protocol, which includes a monitoring period of at least three months.
Exclusion criteria:
Patients with a systolic blood pressure of less than 100 mmHg.
Patients with contraindications to the use of ACE inhibitors, ARBs, and neprilysin inhibitors.
Patients who experience potential side effects or allergic reactions to sacubitril/valsartan or enalapril during treatment.
Patients with renal failure with a GFR of less than 45 ml/min/1.73 m².
Patients with serum potassium levels higher than 5 mmol/L.
Patients who have experienced adverse effects such as angioedema or cough from taking enalapril or other ACE inhibitors.
Patients who develop another serious illness during the intervention and are required to receive various medications that affect the cardiovascular system.
Age
From 18 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Sample size
Target sample size:
86
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization of samples will be conducted based on the block randomization method. The sampling method involves entering information such as the number of treatment groups, block sizes (multiples of the number of groups), and the total number of patients into online software designed for this calculation. Based on the codes obtained from the final analysis, the type of medication received by each patient will be determined. In this study, since there are two treatment groups, blocks of 4 (a multiple of 2) will be used. The anticipated sample size of patients will be randomly divided into two groups: those receiving sacubitril/valsartan and those receiving enalapril, using this sampling method. In this way, according to the order of patient enrollment in the study (based on inclusion criteria), each patient will be assigned a code, and then based on the treatment group assigned to that code in the software output, the patient will be placed in one of the treatment groups for sacubitril/valsartan or enalapril.
Blinding (investigator's opinion)
Double blinded
Blinding description
To ensure the blinding of the study, a clinical pharmacy specialist will design random codes using the relevant online software and inform the clinical pharmacy resident which patient, identified by a specific number, will receive which medication. The medications will then be prepared by the research team, and based on the code assigned to each patient, the prescribed medication will be provided for three months at the outset. During this three-month period, since the patient is under the supervision of the oncologist at Seyed Al-Shohada Center, the clinical pharmacy resident will monitor the patient and ensure adherence to the medication protocol according to the research study plan.
When patients visit the relevant clinics, they will be screened by the research team. If they qualify for entry into the study, they will receive a code based on the randomization process and will collect their medication from the clinical pharmacy resident. The physician responsible for conducting the baseline and three-month echocardiograms (the study physician) will not have any information about the patient's code or the medication being administered. The echocardiographic images and data will be provided to the analyzing physician without mentioning the received medication, solely assigned with a random code for each patient.
Placebo
Not used
Assignment
Parallel
Other design features
This study is a clinical trial. It is anticipated that sample collection will take place over a two-year period (in the years 2024 and 2025) on hospitalized or outpatient patients at the Cardiovascular Research Institute of Isfahan (affiliated with Isfahan University of Medical Sciences) and at the Seyed Al-Shohada Hospital clinic.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Isfahan university of medical sciences
Street address
Isfahan University of medical Sciences, Hezar jarib street, Isfahan, Iran
City
Isfahan
Province
Isfehan
Postal code
8174673461
Approval date
2024-11-25, 1403/09/05
Ethics committee reference number
IR.MUI.PHANUT.REC.1403.123
Health conditions studied
1
Description of health condition studied
Breast cancer patients
ICD-10 code
C50
ICD-10 code description
Malignant neoplasm of breast
Primary outcomes
1
Description
The extent of changes in left ventricular systolic function before and after the intervention
Timepoint
Before the intervention began and after three months of taking either enalapril or sacubitril/valsartan.
Method of measurement
Examination of echocardiographic indices including GLS and assessment of cardiac troponin enzyme.
Secondary outcomes
empty
Intervention groups
1
Description
Intervention Group: Patients with HER2-positive breast cancer undergoing AC treatment will receive Sacubitril/Valsartan at a daily dose of 50 mg for a minimum of three months. These patients are at risk of heart failure due to the use of cardiotoxic medications, and the aim of this intervention is to evaluate the impact of this medication on reducing cardiac complications resulting from cancer treatments. After obtaining informed consent and identification by the interventionist, the medication will be administered randomly and without the patient's knowledge to prevent any bias in the results. Throughout the study, compliance with medication intake will be closely monitored, and if less than 80% compliance is observed, the patient will be withdrawn from the study to ensure the validity of the final data. Additionally, side effects and clinical changes in patients will be regularly monitored.
Category
Prevention
2
Description
Control Group: Patients with HER2-positive breast cancer undergoing AC treatment will receive Enalapril at a daily dose of 5 mg for a minimum of three months. This group also consists of patients who are at risk of heart failure due to cardiotoxic medications, and the purpose of administering Enalapril is to compare its effects with those of Sacubitril/Valsartan in reducing cardiac complications. Similar to the intervention group, after obtaining informed consent and identification, the medication will be administered randomly and without the patient's knowledge. Compliance with medication intake will also be closely monitored, and if less than 80% compliance is observed, the patient will be withdrawn from the study. Furthermore, side effects and clinical changes in these patients will also be regularly monitored to determine the actual impact of treatment on their heart health.
Category
Prevention
Recruitment centers
1
Recruitment center
Name of recruitment center
Seyedoshohadda Hospital
Full name of responsible person
Azadeh Moghaddas
Street address
Daneshgah street
City
Isfehan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3792 7074
Email
azadeh_moghaddas@yahoo.com
2
Recruitment center
Name of recruitment center
Isfahan Cardiovascular Research Institute
Full name of responsible person
Azadeh Moghaddas
Street address
Hezarjarib
City
Isfahan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3792 7074
Email
moghaddas@pharm.mui.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Gholamreza Asgari
Street address
Hezarjarib
City
Isfahan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3668 8138
Email
moghaddas@pharm.mui.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Esfahan University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Azadeh Moghaddas
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
Isfahan University of medical Scienices, Daneshgah street, Isfahan, Iran
City
Isfahan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3792 7074
Email
azadeh_moghaddas@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Azadeh Moghaddas
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
Isfahan University of medical Scienices, Daneshgah street, Isfahan, Iran
City
Isfahan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3792 7074
Email
azadeh_moghaddas@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Azadeh Moghaddas
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
Isfahan University of medical Scienices, Daneshgah street, Isfahan, Iran
City
Isfahan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3792 7074
Email
azadeh_moghaddas@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
All collected data
When the data will become available and for how long
From May 2026
To whom data/document is available
All academic centers
Under which criteria data/document could be used
All documents with citation
From where data/document is obtainable
Email address
What processes are involved for a request to access data/document
After sending a request, we will call the related person and the data will be revealed in less than one week.