Effectiveness evaluation of Tofacitinib plus Remdesivir in comparison with Remdesivir in the treatment of adult patients with severe COVID-19 A randomized double-blind placebo-included clinical trial
Study of Tofacitinib effectiveness in the treatment of sever COVID-19 patients
Design
ِDouble-blind, randomized clinical trial with parallel control group, phase 2-3 on 60 patients. Sealed envelope web-page was used for randomization.
Settings and conduct
The study will be performed in the ICU of Razi Hospital in Rasht from March to June 2021. Sealed envelope web-page is used to allocate treatments to the two arms A and B. 60 patients will be placed in 15 blocks of 4. In intervention group (A) they will receive Tofacitinib 10 mg/day orally for 14 days + Remdesivir 100 mg/day intravenously and in control group (B) they will receive one placebo tablet/day orally for 14 days + Remdesivir 100 mg/day intravenously. Blinding type: Double-blinded. For this purpose an Intensive Care Fellowship prescribes the assigned codes to each patient.
Participants/Inclusion and exclusion criteria
Inclusion criteria: All patients with severe Covid-19 admitted to the ICU of Razi Hospital in Rasht from March to June 2021.
Exclusion criteria: Lack of informed consent; Lack of patient cooperation; Having active tuberculosis, hepatitis B or hepatitis C
Intervention groups
Intervention group: Tofacitinib oral tablet 10 mg daily + Remdesivir IV 100 mg daily for 14 days or hospital discharge (whichever comes first)
Control group: Placebo oral tablet daily + Remdesivir IV 100 mg daily for 14 days or hospital discharge (whichever comes first)
Main outcome variables
The time required to improve clinical symptoms and paraclinical measures within 14 days of starting treatment
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200329046892N2
Registration date:2021-03-09, 1399/12/19
Registration timing:prospective
Last update:2021-03-09, 1399/12/19
Update count:0
Registration date
2021-03-09, 1399/12/19
Registrant information
Name
Nematollah Ahangar
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 13 3369 0099
Email address
n.ahangar@gums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-03-15, 1399/12/25
Expected recruitment end date
2021-06-15, 1400/03/25
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Effectiveness evaluation of Tofacitinib plus Remdesivir in comparison with Remdesivir in the treatment of adult patients with severe COVID-19 A randomized double-blind placebo-included clinical trial
Public title
Effect of tofacitinib in COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
All patients with severe Covid-19 admitted to the ICU of Razi Hospital in Rasht for period of March- June 2021
Age greater than or equal to 18 years
Patients admitted with the following criteria: fever (oral temperature greater than 37.2 ° C), dry cough, severe tiredness or dyspnea
At least one of the following criteria : positive PCR OR lung involvement on chest X-ray / CT scan
Absolute lymphocyte count greater than or equal to 200 per cubic millimeter
Absolute neutrophil count greater than or equal to 1000 per milliliter Cubic meters
Hemoglobin above 8 grams per deciliter
Exclusion criteria:
Lack of informed consent
Lack of patient cooperation
Having pulmonary embolism or intravascular thrombosis
Having another active infection
Having diverticulitis and gastric ulcer
Having tuberculosis or hepatitis B or active hepatitis C or HIV
Any major drug interaction between routine patient's drugs with any of the study drugs
Pregnancy and lactation
Simultaneous presence in other research study
Age
From 18 years old
Gender
Both
Phase
2-3
Groups that have been masked
Participant
Care provider
Outcome assessor
Data analyser
Sample size
Target sample size:
60
Randomization (investigator's opinion)
Randomized
Randomization description
It is a block randomization type and the block with size of 4. Randomization tool: sealedenvelope.com.
60 patients will be assigned in 15 blocks of 4. In intervention group (A) they will receive Tofacitinib 10 mg/day orally for 14 days + Remdesivir 100 mg/day intravenously and in control group (B) they will receive one placebo tablet/day orally for 14 days + Remdesivir 100 mg/day intravenously. Concealment is done using the sealed envelope method.
Blinding (investigator's opinion)
Double blinded
Blinding description
In this study, participants (patients) and medical staff are kept blind to the specificity of study groups (Double-blinded). For this purpose, an independent person from the research team and an Intensive Care Fellowship prescribes the assigned codes to each patient. To ensure the similarity between the drug and the placebo, the placebo is made by the same company. Study drugs will be placed in similar packages, and patients will receive pre-arranged interventions in the order in which they enter the study.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Guilan University of Medical Sciences
Street address
School of Medicine, Guilan University Complex, 7th Km Tehran Road
City
Rasht
Province
Guilan
Postal code
4199613769
Approval date
2021-03-04, 1399/12/14
Ethics committee reference number
IR.GUMS.REC.1399.630
Health conditions studied
1
Description of health condition studied
COVID-19
ICD-10 code
U07.1
ICD-10 code description
virus identified
2
Description of health condition studied
COVID-19
ICD-10 code
U07.2
ICD-10 code description
virus not identified; Clinically-epidemiologically diagnosed COVID-19; Probable COVID-19; Suspected COVID-19
Primary outcomes
1
Description
The time required to improve clinical symptoms and within 14 days of treatment start
Timepoint
Daily from the first day of intervention
Method of measurement
Physical examination
Secondary outcomes
1
Description
Body temperature
Timepoint
Daily from the first day of intervention
Method of measurement
Thermometer
2
Description
Heart rate
Timepoint
Daily from the first day of intervention
Method of measurement
Pulse oxymeter
3
Description
Pulmonary radiological state
Timepoint
Weekly
Method of measurement
CT scan
4
Description
Blood pressure
Timepoint
Daily from the first day of intervention
Method of measurement
Barometer
5
Description
Mechanical ventilation
Timepoint
Daily from the first day of intervention
Method of measurement
Physical examination
6
Description
Duration of hospitalization in the intensive care unit
Timepoint
Daily from the first day of intervention
Method of measurement
Record in the patient file
7
Description
Mortality
Timepoint
Daily from the first day of intervention
Method of measurement
Record in the patient file
8
Description
Respiration rate
Timepoint
Daily from the first day of intervention
Method of measurement
Count
9
Description
Intubation
Timepoint
Daily from the first day of intervention
Method of measurement
Physical examination
10
Description
SPO2
Timepoint
Daily from the first day of intervention
Method of measurement
Pulse-oxy meter
11
Description
D-Dimer
Timepoint
Every 3 days from the first day of intervention
Method of measurement
Fluorescence immunochromatography
12
Description
Creatine phosphokinase
Timepoint
Every 3 days from the first day of intervention
Method of measurement
International Federation of Clinical Chemistry (IFCC)
13
Description
C reactive protein
Timepoint
Every 3 days from the first day of intervention
Method of measurement
Turbidometry
14
Description
Erythrocyte sedimentation rate
Timepoint
Every 3 days from the first day of intervention
Method of measurement
Westergren method
15
Description
Ferritin
Timepoint
Every 3 days from the first day of intervention
Method of measurement
Chemiluminescence method
Intervention groups
1
Description
Intervention group: Tofacitinib10 mg (Rofanib, Nano Alvand ) 1 oral tablet daily + Remdesivir IV 100 mg daily for 14 days or hospital discharge (whichever comes first)
Category
Treatment - Drugs
2
Description
Control group: Placebo (Nano Alvand daru) 1 oral tablet daily + Remdesivir IV 100 mg daily for 14 days or hospital discharge (whichever comes first)
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Razi hospital
Full name of responsible person
Mohammad Haghighi
Street address
Sardar Jangal Ave.
City
Rasht
Province
Guilan
Postal code
4199613769
Phone
+98 13 3354 1001
Email
manesthesist@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Rasht University of Medical Sciences
Full name of responsible person
Dr. Mohammadreza Naghipour
Street address
Shahid Siadati Ave.. Namju St.
City
Rasht
Province
Guilan
Postal code
4144666949
Phone
+98 13 3333 6394
Email
research@gums.ac.ir
Web page address
https://www.gums.ac.ir/research
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Rasht 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
Rasht University of Medical Sciences
Full name of responsible person
Nematollah Ahangar
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Pharmacology
Street address
School of Medicine, Guilan University Complex, 7th Km Tehran road
City
Rasht
Province
Guilan
Postal code
41996-13769
Phone
+98 13 3369 0099
Fax
Email
n.ahangar@gums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Rasht University of Medical Sciences
Full name of responsible person
Nematollah Ahangar
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Pharmacology
Street address
School of Medicine, Guilan University Complex, 7th Km Tehran road
City
Rasht
Province
Guilan
Postal code
4199613769
Phone
+98 13 3369 0099
Fax
Email
n.ahangar@gums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Rasht University of Medical Sciences
Full name of responsible person
Nematollah Ahangar
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Pharmacology
Street address
School of Medicine, Guilan University Complex, 7th Km Tehran road
City
Rasht
Province
Guilan
Postal code
4199613769
Phone
+98 13 3369 0099
Fax
Email
n.ahangar@gums.ac.ir
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
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
Title and more details about the data/document
Data about primary outcome
When the data will become available and for how long
1 month after results publish
To whom data/document is available
Researchers
Under which criteria data/document could be used
Requested by authenticated scientific centers and universities
From where data/document is obtainable
Dr. Nematollah Ahangar School of Medicine
Email: n.ahangar@gums.ac.ir
What processes are involved for a request to access data/document
Official request signed by highest executive is mandatory. Moreover, acceptable reasons should be noted