The effect of pirfenidone on prevention and treatment of pulmonary fibrosis and acute respiratory distress syndrome caused by COVID-19
Design
Randomized clinical trial, with parallel, intervention and control groups, single-blind, simple randomization
Settings and conduct
This is a clinical trial study which will be performed in Golestan and Farabi Hospitals,Kermanshah,Iran.
Pirfenidone 200 mg three times daily, along with standard treatment in the intervention group will be administered for 14 days. Individuals at Control group will recieve the standard treatment for the same period.
Participants/Inclusion and exclusion criteria
Inclusion criteria
o Confirmed cases of COVID-19 who are 18 years and older;
°Not more than 14 days passed from the onset of symptoms
o Bilateral lung involvement
o Moderate to severe ARDS
Exclusion criteria
▪ AST and ALT> 3-5x ULN, bilirubin> 1.5 x ULN at visit
•Creatinine clearance rate at visit 1 <30 mL / min
▪ Previous treatment with nidanib or pirfenidone
▪Significant pulmonary hypertension
▪Cardiovascular diseases, including: ① Severe hypertension within 6 months of Visit 1, uncontrollable after treatment (≥160 / 100 mmHg); ② myocardial infarction and unstable angina
▪History of severe central nervous system events
▪Known trial Drug allergies
▪Patients unable to follow the trial procedures
Intervention groups
Intervention group: Pirfenidone 200 mg ,TDS along with standard treatment (according to the national protocol of Coltra (Lupinavir / Ritonavir)100/400mg twice daily, chloroquine 250 mg twice daily, and siltamivir 75 mg twice daily in critically ill patients with ribavirin 1200 twice daily. )
Patients in the control group will receive standard treatment.
Main outcome variables
Chest CT [ Time Frame: 2 weeks ]Lesion area of chest CT;
Finger pulse oxygen and blood gases[ 2 weeks ]Absolute change in pulse oxygen from baseline;
Dyspnea;fever;cough;malaise.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200314046764N1
Registration date:2020-04-20, 1399/02/01
Registration timing:prospective
Last update:2020-04-20, 1399/02/01
Update count:0
Registration date
2020-04-20, 1399/02/01
Registrant information
Name
Bahareh Baghchi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 83 3835 4444
Email address
bahareh.baghchi@kums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-04-26, 1399/02/07
Expected recruitment end date
2020-05-13, 1399/02/24
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The evaluation of pirfenidone effects on prevention and treatment of pulmonary fibrosis and acute respiratory distress syndrome caused by COVID-19
Public title
Pirfenidine in SARS-COV2
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Confirmed cases of New coronavirus infection or COVID-19 who are 18 years and older;
Not more than 14 days from the onset of symptoms
Bilateral lung involvement in imaging findings
Moderate to severe acute respiratory distress syndrome
Decreased PaO2 to FiO2 ratio
Exclusion criteria:
AST and ALT> 3-5x ULN at visit and bilirubin> 1.5 x ULN at visit
creatinine clearance rate calculated by Cockcroft-Gault formula at visit 1 <30 mL / min
Confirmed previous Idiopathic pulmonary fibrosis,previous treatment with Nidanib or Pirfenidone
Significant pulmonary hypertension (PAH)
Cardiovascular diseases, including any of the following diseases: ① Severe hypertension within 6 months of Visit 1, uncontrollable after treatment (≥160 / 100 mmHg); ② myocardial infarction within 6 months of visit 1; ③ unstable angina within 6 months of visit 1
history of severe central nervous system (CNS) events
known trials Drug allergies
Patients unable to follow the trial procedures
Pregnancy
Breastfeeding
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
40
Randomization (investigator's opinion)
Randomized
Randomization description
In order to prevent bias, a simple randomization method will be used in this study to perform random allocation. We will produce 40 cards , completely identical in appearance. "Number 1" will be written on 20 of them indicating the intervention and on the other 20 cards left, we will write "number 2" which indicates the control group. Each eligible participant then randomly picks one of these cards, which determines how the patients will be randomly assigned to each group. Without the trial participants being informed of the nature of either 1 or 2 numbers.
Blinding (investigator's opinion)
Single blinded
Blinding description
I this study the researcher, questionnaire data recorder, the radiologist evaluating imaging findings, outcome assessors, and data analyser are unaware of patients' affiliation to each group.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Kermanshah University of Medical Sciences
Street address
Branch of researchs and industry,Kermanshah University Of Medical Sciences, Shahid Beheshti Blvd, Kermanshah, Iran
City
Kermanshah
Province
Kermanshah
Postal code
6715847141
Approval date
2020-03-03, 1398/12/13
Ethics committee reference number
IR.KUMS.REC.1399.017
Health conditions studied
1
Description of health condition studied
Pulmonary fibrosis and acute respiratory distress syndrome caused by novel corona-virus pneumonia (COVID-19)
ICD-10 code
B34.2
ICD-10 code description
Coronavirus infection, unspecified
Primary outcomes
1
Description
The scales of pulmonary involvement changes according to the scoring system defined, based on high resolution pulmonary computed tomography before and after the interventions
Timepoint
At visit 1 and then after 14 days.
Method of measurement
Defined scoring system based on pulmonary involvement in high resolution pulmonary CT scan; score one: involvement in less than 5% of a lobe of a lung. Score two: Conflict about 25 percent of a lobe of a lung. Score three: Conflict about 26 to 49 percent of a lobe of a lung. Score four: Conflict about 50 to 75 percent of a lobe of a lung. Score Five: Conflict in more than 75% of a lobe of a lung
Secondary outcomes
1
Description
Changes in arterial gas content
Timepoint
Weekly for 2 weeks
Method of measurement
Paraclinical tests (blood tests)
2
Description
Feeling nauseous
Timepoint
Daily for 14 days
Method of measurement
Through direct questioning of the patient as well as objective observations
3
Description
Shortness of breath
Timepoint
Daily for 14 days
Method of measurement
Through direct questioning of the patient as well as objective observations
4
Description
feeling exhausted
Timepoint
Daily for 14 days
Method of measurement
Through direct questioning of the patient as well as objective observations
5
Description
Shievering
Timepoint
Daily for 14 days
Method of measurement
Through direct questioning of the patient as well as objective observations
6
Description
Cough
Timepoint
Daily for 14 days
Method of measurement
Through direct questioning of the patient as well as objective observations
Intervention groups
1
Description
Intervention group: Pirfenidone 200 mg ,three times daily in addition to standard treatment (according to the national protocol) containing Coltra Lupinavir / Ritonavir twice daily, Chloroquine 250 mg twice daily, and Osiltamivir 75 mg twice daily, in critically ill patients with ribavirin 1200 twice daily. )
Category
Treatment - Drugs
2
Description
Control group: In the control group, standard treatment according to the national protocol containing Coltra (Lupinavir / Ritonavir) 100mg/400mg twice daily, chloroquine 250 mg twice daily, and siltamivir 75 mg twice daily in critically ill patients with ribavirin 1200 twice daily.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Golestan hospital, Kermanshah
Full name of responsible person
Bahareh Baghchi
Street address
Baghabrisham Ave., Parastar Blvd., Medicine school
City
Kermanshah
Province
Kermanshah
Postal code
6715847141
Phone
+98 83 3427 4618
Email
bahareh.baghchi@kums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Kermanshah University of Medical Sciences
Full name of responsible person
Farid Najafi
Street address
Branch of researchs and industry,Kermanshah University Of Medical Sciences, Shahid Beheshti Blvd, Kermanshah, Iran
City
Kermanshah
Province
Kermanshah
Postal code
6715847141
Phone
+98 83 3835 8258
Email
daftarriast@kums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Kermanshah 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
Kermanshah University of Medical Sciences
Full name of responsible person
Bahareh Baghchi
Position
Assistant Professor of emergency medicine
Latest degree
Specialist
Other areas of specialty/work
Emergency Medicine
Street address
Baghabrisham Ave., Parastar Blvd., Medicine school
City
Kermanshah
Province
Kermanshah
Postal code
6715847141
Phone
+98 83 3427 4618
Email
bahareh.baghchi@kums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Kermanshah University of Medical Sciences
Full name of responsible person
Bahareh Baghchi
Position
Assistant Professor
Latest degree
Specialist
Other areas of specialty/work
Emergency Medicine
Street address
Baghabrisham Ave., Parastar Blvd., Medicine school
City
Kermanshah
Province
Kermanshah
Postal code
6715847141
Phone
+98 83 3427 4618
Email
bahareh.baghchi@kums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Kermanshah University of Medical Sciences
Full name of responsible person
Mohammad Nazarian Pirdoosti
Position
nursing student
Latest degree
Bachelor
Other areas of specialty/work
Nursery
Street address
Farabi Hospital, Dollat Abad, Kermanshah, Iran
City
Kermanshah
Province
Kermanshah
Postal code
6715847141
Phone
+98 83 4512 6851
Email
mnazarianpirdosti@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
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