Protocol summary

Study aim
Investigating the efficacy of simultaneous administration of N-acetylcysteine and silymarin compared to N-acetylcysteine alone in liver function improvement in patients with drug-induced liver injury
Design
A clinical trial with a control group and an intervention group, with parallel groups, not blinded, randomized by random block allocation method with Stata software, phase 3 on 130 patients.
Settings and conduct
Kosar Hospital in Karaj,130 patients will randomly be assigned to intervention group (treated with Silymarin and NAC) and control group (treated with NAC). The study is not blinded.
Participants/Inclusion and exclusion criteria
Inclusion criteria: All women and men between the ages of 12 and 80 who have laboratory complications of liver damage caused by drug poisoning in the form of an increase in liver enzymes AST, ALT more than 5 times the upper limit of normal regardless of the presence of clinical symptoms or an increase in AST, ALT, ALKP to twice the upper limit of normal along with total Bilirubin above 2 mg/dL or increase of AST, ALT to the extent of three times the upper limit of normal despite clinical symptoms will be included in the study. Exclusion criteria: 1.Patients with a history of underlying diseases of the Liver and Biliary tract
Intervention groups
Control group: Treated with NAC at a dose of 300mg/kg/day divided every 8 hours from hospitalization until discharge. Intervention group: treated with silymarin (Livergol) at a dose of 70-140 mg every 6 to 8 hours plus NAC at a dose of 300 mg/kg/day divided every 8 hours from admission to discharge
Main outcome variables
Serum levels of AST, ALT, ALKP, Total and direct Bilirubin and clinical symptoms

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20240720062482N1
Registration date: 2024-10-13, 1403/07/22
Registration timing: registered_while_recruiting

Last update: 2024-10-13, 1403/07/22
Update count: 0
Registration date
2024-10-13, 1403/07/22
Registrant information
Name
Ava Doosti
Name of organization / entity
Alborz University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 4400 7481
Email address
ava.doosti1378@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2024-08-22, 1403/06/01
Expected recruitment end date
2024-10-21, 1403/07/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Investigating the efficacy of simultaneous administration of N-acetylcysteine and Silymarin compared to N-acetylcysteine alone in liver function improvement in patients with drug-induced liver injury-clinical trial
Public title
Investigating the efficacy of simultaneous administration of N-acetylcysteine and Silymarin in liver function improvement in patients with drug-induced liver injury
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
All women and men between the ages of 12 and 80 who have laboratory complications of Liver damage caused by Drug poisoning in the form of an increase in Liver enzymes AST, ALT more than 5 times the upper limit of normal, regardless of the presence of clinical symptoms, will be included in the study. All women and men between the ages of 12 and 80 who have laboratory complications of Liver damage caused by drug poisoning in the form of an increase in AST, ALT, and ALKP to twice the upper limit of normal along with total Bilirubin above 2 mg/dl will be included in the study. All women and men between the ages of 12 and 80 who have laboratory complications of Liver damage caused by drug poisoning in the form of an increase in AST, ALT to three times the upper limit of normal despite clinical symptoms (such as loss of appetite, fatigue, weakness and lethargy, nausea and vomiting, abdominal pain preferably epigastric and RUQ, itching, yellow skin or sclera, colorless stool or dark urine) will be included in the study. Since Liver damage caused by drug poisoning may not necessarily have significant and clear clinical symptoms, the preferred entry criterion will be the elevation of Liver enzymes, which will determine the importance of clinical symptoms in decision making.
Exclusion criteria:
Patients with a history of underlying diseases of the Liver and Bile ducts (such as Alcoholic hepatitis, Autoimmune hepatitis, Non-alcoholic fatty liver disease (NAFLD), Viral hepatitis including Hepatitis B virus or Hepatitis C virus).
Age
From 12 years old to 80 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size: 130
Randomization (investigator's opinion)
Randomized
Randomization description
A total of 130 patients with drug-induced liver injury will be randomly assigned to 2 treatment groups using block randomization. Randomization will be performed in the STATA software using the ralloc command in blocks of sizes 6 and 8. Patients will be randomly allocated to the intervention and control groups (A and B). Based on the mentioned method, the allocation order of individuals to the intervention and control groups will be carried out randomly using STATA software. Using the complete command below, randomization of 130 samples into two groups in random blocks of sizes 6 and 8 will be performed. ralloc block size treat, nsubj(130) seed() sav(mytrial) idvar(study_ID) init(6) osize(2) noequal
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Alborz University of Medical Sciences
Street address
Alborz University of Medical sciences, North Taleghani Blvd, Taleghani Sq.
City
Karaj
Province
Alborz
Postal code
3147734568
Approval date
2024-07-10, 1403/04/20
Ethics committee reference number
IR.ABZUMS.REC.1403.098

Health conditions studied

1

Description of health condition studied
Drug-induced Liver injury
ICD-10 code
T96
ICD-10 code description
Sequelae of poisoning by drugs, medicaments and biological substances

Primary outcomes

1

Description
Serum levels of Aspartate aminotransferase(AST)
Timepoint
At the beginning of hospitalization and then daily until discharge from the hospital
Method of measurement
Lab test results in the patient's hospital file

2

Description
Serum levels of Alanine aminotransferase(ALT)
Timepoint
At the beginning of hospitalization and then daily until discharge from the hospital
Method of measurement
Lab test results in the patient's hospital file

3

Description
Serum levels of Alkaline phosphatase(ALP)
Timepoint
At the beginning of hospitalization and then daily until discharge from the hospital
Method of measurement
Lab test results in the patient's hospital file

4

Description
Serum levels of Total Bilirubin
Timepoint
At the beginning of hospitalization and then daily until discharge from the hospital
Method of measurement
Lab test results in the patient's hospital file

5

Description
Serum levels of Direct Bilirubin
Timepoint
At the beginning of hospitalization and then daily until discharge from the hospital
Method of measurement
Lab test results in the patient's hospital file

Secondary outcomes

1

Description
Clinical symptoms caused by hepatotoxicity (Loss of appetite, fatigue, weakness and lethargy, nausea and vomiting, abdominal pain preferably in the Epigastrium and RUQ, itching, yellowing of the skin or sclera, colorless stool or dark urine)
Timepoint
At the beginning of hospitalization and then during daily visits of patient until discharge from the hospital
Method of measurement
By taking a history from the patient and asking the patient about the mentioned symptoms and during clinical examinations on daily visits

Intervention groups

1

Description
Control group: The patients of this group will be treated with N-acetylcysteine (NAC) at a dose of 300mg/kg/day divided every 8 hours. This treatment will start when the patient is hospitalized and will continue until the patient is discharged from the hospital. The group will be monitored daily for clinical symptoms and liver profile tests, and the information obtained will be recorded in the checklists.
Category
Treatment - Drugs

2

Description
Intervention group: Patients in this group will be treated with Silymarin (Livergol) at a dose of 70-140 mg every 6 to 8 hours plus N-acetylcysteine (NAC) at a dose of 300 mg/kg/day divided every 8 hours. This treatment will start when the patient is hospitalized and will continue until the patient is discharged from the hospital. The patients of this group will be monitored daily for clinical symptoms and liver profile tests, and the information obtained will be recorded in the checklists.
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Kosar Hospital
Full name of responsible person
Dr.Lida Shojaei
Street address
Kharazmi Blvd, Hesarak Quarter.
City
Karaj
Province
Alborz
Postal code
3197914795
Phone
+98 26 3428 4761
Email
kosarhp@abzums.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Karaj University of Medical Sciences
Full name of responsible person
Dr.Lida Shojaei
Street address
Alborz University of Medical sciences, North Taleghani Blvd, Taleghani Sq.
City
Karaj
Province
Alborz
Postal code
3147734568
Phone
+98 26 3419 8000
Email
l.shojaei52@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Karaj 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
Karaj University of Medical Sciences
Full name of responsible person
Ava Doosti
Position
Medical Student(Intern)
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
Unit 20, No.7, before the 8th Alley, Hasan Abad St, East Ferdous Blvd
City
Tehran
Province
Tehran
Postal code
1481838964
Phone
+98 21 4400 7481
Fax
Email
Ava.doosti1378@gmail.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Karaj University of Medical Sciences
Full name of responsible person
Dr.Lida Shojaei
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Forensic Medicine
Street address
Alborz University of Medical Sciences, North Taleghani Blvd, Taleghani Sq.
City
Karaj
Province
Alborz
Postal code
3147734568
Phone
+98 26 3419 8000
Email
l.shojaei52@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Karaj University of Medical Sciences
Full name of responsible person
Ava Doosti
Position
Medical Student(Intern)
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
Unit 20, No.7, before the 8th Alley, Hasan Abad St, East Ferdous Blvd
City
Tehran
Province
Tehran
Postal code
1481838964
Phone
+98 21 4400 7481
Fax
Email
Ava.doosti1378@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be a plan to make this available
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