Evaluation of oral silymarin formulation efficacy in prevention of hepatotoxicity induced by doxorubicin containing chemotherapy regimen in patients with non-metastatic breast cancer
Evaluation of oral silymarin formulation efficacy in prevention of hepatotoxicity induced by doxorubicin containing chemotherapy regimen in patients with non-metastatic breast cancer
Design
This is a randomized triple-blind, parallel group clinical trial on 50 patients with non-metastatic breast cancer (25 patients in treatment group and 25 patients in placebo group).
Settings and conduct
This study will be performed on 50 non-metastatic breast cancer patients referring to Imam Reza Hospital, Mashhad, Iran. They whether will receive 3 silymarin 140mg tablets for 4 courses in treatment group or 3 placebo tablets in placebo group.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
1. Non-metastatic breast cancer undergoes chemotherapy with a regimen containing doxorubicin after a mastectomy.
2. Age between 18 to 65 years
3. Signing the informed consent by the patient
Non-Inclusion criteria:
1. Viral hepatitis
2. History of allergy to silymarin or other similar compounds
3. Pregnancy or lactation
4. Liver involvement grade 2 or higher based on liver ultrasound
5. Chronic liver disease and cirrhosis (Child-Pugh B and C classes),
6. Hepatic-biliary obstruction
7. Renal failure (GFR <30 mL/min)
8. Malabsorption syndrome or GI obstruction
9- Concomitant use of hepatotoxic or antioxidant medications
Exclusion criteria:
1. Changing the chemotherapy regimen
2. The patient unwillingness for medication use
3. Severe adverse drug reactions
4. Inability of the patient to swallow oral medication
5. Uncontrolled vomiting
Intervention groups
Intervention group: 420mg silymarin daily (three livergol 140mg tablets daily) during 4 courses of chemotherapy
Placebo group: three placebo tablets/day for 4 courses of chemotherapy (with same appearance of livergol tablet containing all livergol ingredients except silymarin)
Main outcome variables
liver enzymes serum level & ultrasound
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200408046990N6
Registration date:2021-01-13, 1399/10/24
Registration timing:prospective
Last update:2021-01-13, 1399/10/24
Update count:0
Registration date
2021-01-13, 1399/10/24
Registrant information
Name
Sepideh Elyasi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 51 3180 1588
Email address
elyasis@mums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-01-20, 1399/11/01
Expected recruitment end date
2021-08-23, 1400/06/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of oral silymarin formulation efficacy in prevention of hepatotoxicity induced by doxorubicin containing chemotherapy regimen in patients with non-metastatic breast cancer
Public title
Evaluation of silymarin tablet efficacy in prevention of hepatotoxicity induced by doxorubicin containing chemotherapy regimen in patients with non-metastatic breast cancer
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Age between 18-65 y
Patients with diagnosis of non-metastatic breast cancer who will be treated by doxurobicin after mastectomy
Signing the written consent
Exclusion criteria:
Viral hepatitis
History of hypersensitivity to silymarin or similar compounds
Pregnancy and lactation
Liver involvement grade 2 or higher based on ultrasound evaluation
Any kind of liver injury resulting in rise of liver enzymes or bilirubin to higher than upper limit normal
Hepatobiliary obstruction
Renal failure (GFR<30 mL/min)
Malabsorption syndrome
Concomitant use of heptotoxic agents or antioxidants
Age
From 18 years old to 65 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
50
Randomization (investigator's opinion)
Randomized
Randomization description
Patients with inclusion criteria of the study will be recruited in the intervention or the control group according the permuted block randomization (10 blocks and 3 patients in each block)
Blinding (investigator's opinion)
Triple blinded
Blinding description
The silymarin and placebo tablets (prepared by Mashhad Pharmacy School) will be packaged in boxes with same appearance and delivered to the clinician. Patients who meet the inclusion criteria are selected by clinician to be included in the study and will receive a box filled with medication or placebo respectively. Patients will be evaluated during the treatment course by the physician. Data collection and analysis will be performed by the pharmacy student and the clinical pharmacist. All of them will be unaware patients' grouping until the end of the study and data analysis.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Mashhad University of Medical Sciences
Street address
Qureshi Building, Daneshgah street
City
Mashhad
Province
Razavi Khorasan
Postal code
1394491388
Approval date
2020-12-05, 1399/09/15
Ethics committee reference number
IR.MUMS.REC.1399.527
Health conditions studied
1
Description of health condition studied
hepatotoxicity
ICD-10 code
K71.1
ICD-10 code description
Toxic liver disease with hepatic necrosis, with coma
Primary outcomes
1
Description
Serum level of hepatic transaminases, total billirubin, direct billirubin, prothrombin time, serum albumin, alkalin phosphatase
Timepoint
At the beginning of the study, 2 weeks after the beginning of study, one month after the beginning of the study
Method of measurement
Serum level measurement by the laboratory
2
Description
Liver ultrasound to determine the stage of the fatty liver
Timepoint
At the beginning of the study, one month after the beginning of the study
Method of measurement
Ultrasound evaluation
Secondary outcomes
1
Description
Serum level of creatinine and urea
Timepoint
At the beginning of the study, 2 weeks after the beginning of study, one month after the beginning of the study
Method of measurement
Serum level measurement by the laboratory
Intervention groups
1
Description
Intervention group: Livergol 140 mg three tablets daily after meals (produced by Goldaroo company), oral, for 4 weeks
Category
Treatment - Drugs
2
Description
Control group: Placebo tablets for Livergol, three tablet daily after meals, for 4 week, oral
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Reza hospital, affiliated to Mashhad University of Medical Sciences
Full name of responsible person
Sepideh Elyasi
Street address
Imam Reza Sq.
City
Mashhad
Province
Razavi Khorasan
Postal code
9137913316
Phone
+98 51 3854 3031
Fax
Email
elyasis@mums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Mashhad University of Medical Sciences
Full name of responsible person
Mohsen Tafaghodi
Street address
Faculty of Pharmacy, Ferdowsi University, Vakilabad Boulevard
City
Mashhad
Province
Razavi Khorasan
Postal code
17871 91886
Phone
+98 51 3180 1337
Email
tafaghodim@mums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Mashhad 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
Mashhad University of Medical Sciences
Full name of responsible person
Sepideh Elyasi
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of Pharmacy; Ferdowsi University; Vakilabad Boulevard
City
Mashhad
Province
Razavi Khorasan
Postal code
17871 91886
Phone
+98 51 3180 1588
Email
elyasis@mums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Mashhad University of Medical Sciences
Full name of responsible person
Sepideh Elyasi
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of Pharmacy; Ferdowsi University; Vakilabad Boulevard
City
Mashhad
Province
Razavi Khorasan
Postal code
17871 91886
Phone
+98 51 3180 1588
Email
elyasis@mums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Mashhad University of Medical Sciences
Full name of responsible person
Sepideh Elyasi
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of Pharmacy; Ferdowsi University; Vakilabad Boulevard
City
Mashhad
Province
Razavi Khorasan
Postal code
17871 91886
Phone
+98 51 3180 1588
Email
elyasis@mums.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
No - There is not a plan to make this available
Title and more details about the data/document
The findings will be published in an article. Study protocol and statistical analysis will be used for article publication.
When the data will become available and for how long
One year after the end of the study it will be published and available in databases.
To whom data/document is available
If the funding sponsor allowed, the findings will be available for researchers, clinicians, and scientific centers.
Under which criteria data/document could be used
The other researchers can use our findings in their review articles and meta analysis.
From where data/document is obtainable
For this purpose, you can contact with Sepideh Elyasi, at Clinical Pharmacy Department, School of Pharmacy, Vakil Abad Aven., Mashhad, Iran. Email: elyasis@mums.ac.ir
What processes are involved for a request to access data/document
After receiving the query, dependent on the requested data, the scientific responsible person of the study will response to the query in coordinate with the sponsor within 2 weeks