Acetylcysteine for the Prevention of Liver Injury in Covid-19 Intensive Care Unit Patients Under Treatment with Remdisivir: A Double-Blind, Placebo-Controlled Randomized Clinical Trial
1. To compare serum levels of liver aminotransferases, bilirubin and prothrombin time between Covid-19 patients receiving remdesivir with and without simultaneous acetylcysteine therapy
2. To compare the incidence of acute liver injury between Covid-19 patients receiving remdesivir with and without simultaneous acetylcysteine therapy
Design
A double-blind, placebo-controlled randomized clinical trial.
Patients will be randomized using QuickCalcs random-number calculators (2018 GraphPad Software, LLC; San Diego, CA).
Settings and conduct
Intensive care unit of Imam Reza Hospital (501 Hospital, AJA University of medical Sciences)
Participants/Inclusion and exclusion criteria
َAll patients aged above 18 years admitted in intensive care unit with definite diagnosis of Covid-19 under treatment with remdesivir will be included.
Criteria of exclusion will be:
1. Positive history of any underlying liver disease
2. Plasma levels of liver transaminases over 100 IU/L on the first day of ICU admission
3. Simultaneous use of any hepatotoxic drugs
Intervention groups
One gram acetylcysteine will be administered intravenously every 12 hours for each patient in the intervention group, and each patient in the placebo group will receive the same volume of 0.9% sodium chloride.
Main outcome variables
Outcome of interest will be considered as any significant difference in serum levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, prothrombin time or incidence rate of acute liver injury between intervention and placebo groups on the second, third, forth or fifth day of trial.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20210726051995N1
Registration date:2021-08-15, 1400/05/24
Registration timing:registered_while_recruiting
Last update:2021-08-15, 1400/05/24
Update count:0
Registration date
2021-08-15, 1400/05/24
Registrant information
Name
Ebrahim Hazrati
Name of organization / entity
َAJA University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 8802 8350
Email address
dr.hazrati.e@ajaums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-07-27, 1400/05/05
Expected recruitment end date
2021-09-27, 1400/07/05
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Acetylcysteine for the Prevention of Liver Injury in Covid-19 Intensive Care Unit Patients Under Treatment with Remdisivir: A Double-Blind, Placebo-Controlled Randomized Clinical Trial
Public title
Acetylcysteine for the Prevention of Liver Injury in Covid-19 Patients
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Diagnosed positive for Covid-19 based on PCR testing
Admitted in intensive care unit
Treated with remdesivir
Exclusion criteria:
Positive history of any underlying liver disease e.g. fatty liver, or acute or chronic hepaptitis
Plasma levels of liver transaminases over 100 IU/L on the first day of ICU admission
Simultaneous use of any hepatotoxic drugs
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
88
Randomization (investigator's opinion)
Randomized
Randomization description
QuickCalcs random-number calculators (2018 GraphPad Software, LLC; San Diego, CA) will be used for randomization. In this regard, patients will receive random numbers of 0 or 1 generated by the software, and will be included into either intervention or control groups accordingly.
Blinding (investigator's opinion)
Double blinded
Blinding description
The study patients, principle investigator, responsible physician and the intensive care unit nursing staff will stay blinded until the end of the trial.
Only the chief pharmacist will be aware of the patients' groups, and will provide medications to the nursing staff in identical individually numbered packs, containing either acetylcysteine or normal saline (placebo) according to the sequential order of the randomization.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics committee of AJA University of Medical Sciences
Street address
AJA University of Medical Sciences, Etemadzadeh Ave., West Fatemi St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1411718541
Approval date
2021-07-26, 1400/05/04
Ethics committee reference number
IR.AJAUMS.REC.1400.092
Health conditions studied
1
Description of health condition studied
COVID-19 pneumonia
ICD-10 code
J12.81
ICD-10 code description
Pneumonia due to SARS-associated coronavirus
2
Description of health condition studied
Acute liver injury
ICD-10 code
K72.0
ICD-10 code description
Acute and subacute hepatic failure
Primary outcomes
1
Description
the prevention of acute liver injury
Timepoint
Days 1, 2, 3, 4 and 5 of trial
Method of measurement
Laboratory measurement of serum levels of liver aminotransferases
Secondary outcomes
1
Description
Total bilirubin serum levels
Timepoint
Days 1, 2, 3, 4 and 5 of trial
Method of measurement
Laboratory measurement
2
Description
Prothrombin time
Timepoint
Days 1, 2, 3, 4 and 5 of trial
Method of measurement
Laboratory measurement
Intervention groups
1
Description
Intervention group: including 44 patients who will receive 1000 mg of acetylcysteine intravenously every 12 hours for 5 days.
Category
Treatment - Drugs
2
Description
Control group: including 44 patients who will receive placebo (Normal Saline, 0.9%) intravenously every 12 hours for 5 days.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Reza Hospital
Full name of responsible person
Pouria Mousapour
Street address
Imam Reza Hospital, Etemadzadeh Ave., West Fatemi St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1411718541
Phone
+98 21 8609 6350
Email
p_mousapour@sbmu.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Artesh University of Medical Sciences
Full name of responsible person
Mojtaba Yousefi Zoshk
Street address
AJA University of Medical Sciences, Etemadzadeh Ave., West Fatemi St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1411718541
Phone
+98 21 8609 6350
Email
dr.yousefi.md@ajaums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Artesh 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
Artesh University of Medical Sciences
Full name of responsible person
Ebrahim Hazrati
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Intensive care
Street address
AJA University of Medical Sciences, Etemadzadeh Ave., West Fatemi St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1411718541
Phone
+98 21 8609 6350
Email
dr.hazrati.e@ajaums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Artesh University of Medical Sciences
Full name of responsible person
Pouria Mousapour
Position
General practitioner
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
AJA University of Medical Sciences, Etemadzadeh Ave., West Fatemi St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1411718541
Phone
+98 21 8609 6350
Email
p_mousapour@sbmu.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Artesh University of Medical Sciences
Full name of responsible person
Pouria Mousapour
Position
General Practitioner
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
AJA University of Medical Sciences, Etemadzadeh Ave., West Fatemi St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1411718541
Phone
+98 21 8609 6350
Email
p_mousapour@sbmu.ac.ir
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
No - There is not 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