A prospective randomized controlled trial comparing antiviral Sovodak (Sofosbuvir+Daclatasvir) in participants with moderate to severe Coronavirus disease (COVID-19) compared to standard of care treatment
To evaluate whether Sovodak (Sofosbuvir+Daclatasvir) increased significant clinical and radiological 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-blinded, single center study. 70 patients are enrolled and followed for 14 days.
Settings and conduct
The study will be conducted in a tertiary center (Shariati hospital) by investigators of digestive disease research institute (TUMS) and the Ministry of Health and Medical Education of Iran.
Radiologists, physicians who assess outcomes and the statistician analyzing the data all 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.
Included: age ≥ 18y, symproms: fever ≥ 38.0 ℃ and at least one of: respiratory rate >24/min or cough or dyspnea or O2Sat<93% or the Pa02/Fi02 ratio <300mgHg, PCR confirmed, diagnostic chest CT scan
Excluded: known allergic reaction to intervention drug, pregnant or breastfeeding, any prior experimental treatment for COVID-19, heart rate<60/min, taking Amiodarone
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
Significant clinical and radiologic recovery (composite):
Clinical recovery up to 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), and alleviation of cough (mild or absent on a patient reported scale), sustained for at least 72 hours.
General information
Reason for update
Acronym
COVID-19-DAA-RCT =CDR-19
IRCT registration information
IRCT registration number:IRCT20200128046294N2
Registration date:2020-03-14, 1398/12/24
Registration timing:prospective
Last update:2020-03-14, 1398/12/24
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
2020-03-15, 1398/12/25
Expected recruitment end date
2020-04-13, 1399/01/25
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A prospective randomized controlled trial comparing antiviral Sovodak (Sofosbuvir+Daclatasvir) in participants with moderate to severe Coronavirus disease (COVID-19) compared to standard of care treatment
Public title
Comparing antiviral agent in the treatment of COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Both genders
Age ≥18 years at time of signing Informed Consent Form
Willingness of study participant to accept randomization to any assigned treatment arm
Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of study
Will be admitted to the hospital within 72 hours and not transferred to another hospital
Laboratory (RT-PCR) confirmed infection with 2019-nCoV
Lung involvement confirmed with chest imaging
Hospitalized patients with: Fever Oral temperature ≥ 38.0 ℃. And at least one of Respiratory rate >24/min / O2Sat<93% or the Pa02/Fi02 ratio <300mgHg / Dyspnea / Cough
≤8 days since illness onset
Exclusion criteria:
Known allergic reaction to Sofosbuvir or Kaletra
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
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
Randomization (investigator's opinion)
Randomized
Randomization description
Patients will be simply 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 (reading letters) will be recorded.
Blinding (investigator's opinion)
Double 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
Ethics committee of Digestive Disease Research Institute - Tehran University of Medical Sciences
Street address
Digestive Disease Research Institute, Shariati Hospital, Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1411713135
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
2019-nCoV acute respiratory disease
Primary outcomes
1
Description
time to Significant clinical recovery (composite primary endpoint)
Timepoint
time frame: up to 14 days after starting the trial
Method of measurement
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), and alleviation of cough (mild or absent on a patient reported scale), sustained for at least 72 hours.
2
Description
time to radiological improvement
Timepoint
day 14
Method of measurement
Comparing baseline and day 14 of chest CT scan assessed by two radiologist described by a quantitative system
Secondary outcomes
1
Description
Frequency of requirement for mechanical ventilation
Timepoint
day 28
Method of measurement
Yes/No
2
Description
Frequency of respiratory progression
Timepoint
day 28
Method of measurement
Yes/No
3
Description
Frequency of serious adverse events
Timepoint
Any time during study up to day 28
Method of measurement
Assessment of adverse events specifically related to the disease, as well as medications through history taking and physical examination
4
Description
All-cause mortality
Timepoint
day 28
Method of measurement
Frequency (٪)
Intervention groups
1
Description
Control group: Standard of care treatment including Kaletra (Lopinavir 400mgA/Ritonavir 100mg) BID *14days oral + Oseltamivir 75mg BID *5 days + Hydroxy Chloroquine 400mg single dose ± Antibiotics
Category
Treatment - Drugs
2
Description
Intervention group: Sovodak, Company: Rojan, Daily single oral tablet containing 400mg of Sofosbovir and 60mg of Daclatasvir + Standard of care treatment
Category
Treatment - Surgery
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 8490 1000
Fax
+98 21 8863 3039
Email
shariatihosp@tums.ac.ir
Web page address
http://shariati.tums.ac.ir/
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Rojan Pharmed
Full name of responsible person
Rojan Pharmed
Street address
Number 10,5th floor, block 8, Hamedan Street, North Kargar Street, Tehran
City
Tehran
Province
Tehran
Postal code
1418693918
Phone
+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
Rojan Pharmed
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
2
Sponsor
Name of organization / entity
Ministry of Health and Medical Education, Tehran, Iran
Full name of responsible person
Ministry of Health and Medical Education, Tehran, Iran
Street address
Tehran Province, Tehran, District 2, Eyvanak Blvd, Iran
City
Tehran
Province
Tehran
Postal code
1467664961
Phone
+98 21 8836 3714
Fax
+98 21 8836 3715
Email
iad@mohme.gov.ir
Web page address
http://iad.behdasht.gov.ir/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Ministry of Health and Medical Education, Tehran, Iran
Proportion provided by this source
5
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
Other
3
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
40
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
Academic
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
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
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
No - There is not a plan to make this available
Clinical Study Report
Not applicable
Analytic Code
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
The Protocol and Statistical Analytic Plan (SAP) will be shared.
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
The Protocol and Statistical Analytic Plan (SAP) will be publically available.