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Protocol summary

Study aim
To evaluate whether Sovodak (Sofosbuvir plus Daclatasvir) increases significant clinical improvement as compared to standard of care in hospitalized patients with moderate to severe COVID-19.
Design
This is a parallel 2-arm randomized, controlled, double-blind, multi center study. 70 patients are enrolled and followed for 14 days.
Settings and conduct
The study will be conducted in Shariati hospital (Tehran), Baharloo (Tehran), Sina (Tehran), Sayyad Shirazi (Gorgan) by investigators of digestive disease research institute (TUMS). Radiologists, physicians who assess outcomes and the statistician analyzing the data will be blinded but the patients and physicians who treat patients will know the assigned treatment group.
Participants/Inclusion and exclusion criteria
All moderate to severe COVID-19 infected patients admitted to Shariati hospital (Tehran), Baharloo (Tehran), Sina (Tehran), Sayyad Shirazi (Gorgan) Inclusion criteria: age ≥ 18y; hospitalized patients with: Fever (Oral temperature ≥ 37.8 ℃) and at least one of Respiratory rate >24/min / O2Sat<94% or the Pa02/Fi02 ratio <300mgHg; PCR confirmed; diagnostic chest CT scan. Exclusion criteria: known allergic reaction to intervention drug, pregnant or breastfeeding, any prior experimental treatment for COVID-19, heart rate<60/min, taking Amiodarone, evidence of multiorgan failure, requiring mechanical ventilation at screening, eGFR< 50 mL/min
Intervention groups
70 eligible patients with moderate to severe COVID-19 in a 1:1 ratio: • Standard of care treatment • Sovodak tablet (Sofosbuvir 400mg/Daclatasvir 60mg) + Standard of care treatment
Main outcome variables
Clinical recovery (composite) within 14 days from initiation of study treatment until normalization of fever (≤37.2 °C oral), respiratory rate (≤24/minute on room air), and oxygen saturation (≥94% on room air), sustained for at least 24 hours.

General information

Reason for update
The trial was completed.
Acronym
IRCT registration information
IRCT registration number: IRCT20200128046294N2
Registration date: 2020-03-14, 1398/12/24
Registration timing: prospective

Last update: 2020-06-01, 1399/03/12
Update count: 4
Registration date
2020-03-14, 1398/12/24
Registrant information
Name
Anahita Sadeghi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8241 5104
Email address
a-sadeghi@tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-03-26, 1399/01/07
Expected recruitment end date
2020-06-20, 1399/03/31
Actual recruitment start date
2020-03-26, 1399/01/07
Actual recruitment end date
2020-04-26, 1399/02/07
Trial completion date
2020-05-18, 1399/02/29
Scientific title
A prospective randomized controlled trial comparing Sovodak (Sofosbuvir plus Daclatasvir) in participants with moderate to severe Coronavirus disease (COVID-19) compared to standard of care treatment
Public title
Study to Evaluate the Safety and Efficacy of Sofosbuvir/Daclatasvir in Participants with Moderate to Severe Coronavirus Disease (COVID-19)
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Both genders Age ≥18 years at time of signing Informed Consent Form Willing and able to provide written informed consent prior to performing study to any assigned treatment arm Must agree not to enroll in another study of an investigational agent prior to completion of study Will be admitted to Shariati hospital (Tehran), Baharloo (Tehran), Sina (Tehran), Sayyad Shirazi (Gorgan) and not transferred to another hospital Laboratory (RT-PCR) confirmed infection with 2019-nCoV Lung involvement confirmed with chest CT scan Hospitalized patients with: Fever (Oral temperature ≥ 37.8 ℃) and at least one of Respiratory rate >24/min / O2Sat<94% or the Pa02/Fi02 ratio <300mgHg ≤8 days since illness onset
Exclusion criteria:
Known allergic reaction to Sofosbuvir or Daclatasvir Pregnant or breastfeeding, or positive pregnancy test Receipt of any experimental treatment for COVID-19 prior to the time of the screening evaluation Heart rate < 60/min Taking Amiodarone Evidence of multiorgan failure Requiring mechanical ventilation at screening eGFR< 50 mL/min
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
  • Investigator
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 70
Actual sample size reached: 70
Randomization (investigator's opinion)
Randomized
Randomization description
Patients will be randomized in a 1:1 ratio into one of the treatment groups and standard of care group using computer generated randomization plan. The date and time of randomization will be recorded. Allocation concealment will be done with the sealed envelope method.
Blinding (investigator's opinion)
Single blinded
Blinding description
The treatment assignment will remain unknown until the patient is randomized. Physicians who treat patients and the patients will not be blinded. Radiologists, physicians who assess outcomes and the statistician analyzing the data all will be blinded.
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Institutional Research Ethics Committee, Vice-Chancellor in Research Affairs- Tehran University of M
Street address
Central Building of Tehran University of Medical Sciences: No. 226, Qods St., Keshavarz Blvd., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1416753955
Approval date
2020-03-11, 1398/12/21
Ethics committee reference number
IR.TUMS.VCR.REC.1398.1035

Health conditions studied

1

Description of health condition studied
COVID-19
ICD-10 code
U07.1
ICD-10 code description
COVID-19

Primary outcomes

1

Description
Clinical recovery (composite) within 14 days from initiation of study treatment until normalization of fever (≤37.2 °C oral), respiratory rate (≤24/minute on room air), and oxygen saturation (≥94% on room air), sustained for at least 24 hours.
Timepoint
daily up to 14 days after starting the trial
Method of measurement
Clinical examination

Secondary outcomes

1

Description
Requirement for mechanical ventilation
Timepoint
daily up to day 14
Method of measurement
Clinical evaluation

2

Description
Radiological changes
Timepoint
day 14 or sooner at the discretion of the physician
Method of measurement
Chest CT scan

3

Description
Serious adverse events
Timepoint
Any time during study up to day 14
Method of measurement
Clinical evaluation

4

Description
All-cause mortality
Timepoint
Any time during study up to day 14
Method of measurement
Clinical evaluation

Intervention groups

1

Description
Control group: Standard of care treatment according to the national guidelines for the treatment of COVID-19
Category
Treatment - Drugs

2

Description
Intervention group: Sovodak, Company: Rojan, Daily single oral tablet containing 400mg of Sofosbovir and 60mg of Daclatasvir plus Standard of care treatment
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Shariati Hospital
Full name of responsible person
Dr Anahita Sadeghi
Street address
Shariati Hospital, North Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Fax
+98 21 8241 5400
Email
a-sadeghi@tums.ac.ir
Web page address

2

Recruitment center
Name of recruitment center
Sina Hospital
Full name of responsible person
Mahnaz Montazeri
Street address
Sina Hospital, Hassan Abad Square, Imam Khomeini Ave, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1136746911
Phone
+98 21 6634 8500
Email
mahnazmontazeri@yahoo.com

3

Recruitment center
Name of recruitment center
Baharloo hospital
Full name of responsible person
Hadiseh Hosemi Roudsari
Street address
Baharloo Hospital - Behdari.street - Railway.square
City
Tehran
Province
Tehran
Postal code
1339973111
Phone
+98 21 5565 8500
Email
h-hosami@tums.ac.ir
Web page address

4

Recruitment center
Name of recruitment center
Sayad Shirazi Hospital
Full name of responsible person
Alireza Norouzi
Street address
Shahid Sayyad Shirazi Boulevard
City
Gorgan
Province
Golestan
Postal code
4917867439
Phone
+98 17 3226 1175
Email
norouzi54@gmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Digestive Disease Research Institute
Full name of responsible person
Dr Anahita Sadeghi
Street address
Digestive Disease Research Institute, Shariati Hospital, Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Fax
+98 21 8241 5400
Email
info@ddri.ir
Web page address
https://ddri.ir/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Digestive Disease Research Institute
Proportion provided by this source
50
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

2

Sponsor
Name of organization / entity
Fannavaran Rojan Mohaghegh Daru
Full name of responsible person
Fannavaran Rojan Mohaghegh Daru
Street address
Number 10, block 8, Hamedan Street, North Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1418693918
Phone
+98 21 6658 2689
Fax
+98 21 6658 2689
Email
info@rojanpharma.com
Web page address
https://sovodak.com/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Fannavaran Rojan Mohaghegh Daru
Proportion provided by this source
50
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry

Person responsible for general inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Hossein Poustchi
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Epidemiology
Street address
Shariati Hospital, Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Email
h.poustchi@gmail.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Shirin Afhami
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Infectious diseases
Street address
Shariati Hospital, Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 2557
Email
afhamish@tums.ac.ir

Person responsible for updating data

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Anahita Sadeghi
Position
Assistant Professor
Latest degree
Subspecialist
Other areas of specialty/work
Internal Medicine
Street address
Shariati Hospital, Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5176
Email
anahita825@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
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
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
The study protocol, statistical analytic plan informed consent forms will be shared as supplementary material at the time of publication of results.
When the data will become available and for how long
At the time of publication
To whom data/document is available
Will be publically available as a supplement accompanying the published article.
Under which criteria data/document could be used
To interpret the findings of published study, and to use as a reference for future research
From where data/document is obtainable
On the website of journal that will publish the research
What processes are involved for a request to access data/document
They will be publically available.
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