Comparison of the efficacy and safety of Atazanavir/Ritonavir plus Hydroxychloroquine regimen with Lopinavir/Ritonavir plus Hydroxychloroquine regimen in patients with moderate COVID-19, A randomized, double-blind study
Comparison of the efficacy and safety of Atazanavir/Ritonavir +HCQ with Lopinavir/Ritonavir +HCQ in patients with moderate COVID-19
Design
A randomized, double-blind, parallel phase 3 clinical trial is conducted on 128 patients with moderate COVID-19. Sealed envelope online software was used to randomize the allocation of treatment to the two intervention arms.
Settings and conduct
Patients dyspnea and O2Sat less than 94% with possibly lung CT scan evidence of moderate COVID-19 pneumonia (Involvement of a maximum of 3 or 4 lung lobes with an area less than 1/3 size of each lobe or involvement of 1or 2 lobes with more involvement) and refer to Razi Hospital in Ghaemshahr in the 2020 epidemic, will be enrolled in the study. Researcher and final assessor are blind to the type of intervention and the allocation of treatment is under the supervision of a physician.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Signing a written consent form; Age 18-75 years; Moderate COVID-19
Exclusion criteria: History of hospitalization due to COVID-19; Participate in any other clinical trial of COVID-19 treatment; Patients under mechanical ventilation at baseline; Sensitivity to atazanavir; Active cancer; Immune system compromised; Abnormal baseline ECG; Pregnancy and lactation; Renal failure; Severe liver failure; multi-organ failure; Concomitant use of CYP3A4 inducers
Intervention groups
In group A, 400 mg of hydroxychloroquine on the first day and Kaletra 2 tablets every 12 hours for 5 days, and in group B, hydroxychloroquine 400 mg single dose on the first day and atazanavir/ritonavir daily were administered for at least 5 days.
Main outcome variables
Primary Outcome: Recovery within 10 days of starting treatment
Secondary outcomes: Improvement within 14 days after starting treatment; Survival rate; Number of days hospitalized; Number of days of intubated; Number of days in the ICU
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200328046886N2
Registration date:2020-10-12, 1399/07/21
Registration timing:registered_while_recruiting
Last update:2020-10-12, 1399/07/21
Update count:0
Registration date
2020-10-12, 1399/07/21
Registrant information
Name
Hamideh Abbaspour
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 11 4203 1035
Email address
dr.abbaspour1@yahoo.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-08-22, 1399/06/01
Expected recruitment end date
2020-11-21, 1399/09/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of the efficacy and safety of Atazanavir/Ritonavir plus Hydroxychloroquine regimen with Lopinavir/Ritonavir plus Hydroxychloroquine regimen in patients with moderate COVID-19, A randomized, double-blind study
Public title
Evaluation of the efficacy and safety of Atazanavir/Ritonavir plus Hydroxychloroquine regimen in patients with moderate COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Getting out the informed consent form from all of the patients or their guardian
Aged between 18 to 75
Having one of the following symptoms: Dry cough, Severe weakness or fatigue, Dyspnea, Feeling of pain and pressure on the chest, With or without fever greater than 38° C
Days from onset of the symptoms equal or less than 7
Definitive diagnosis of moderate COVID-19 based on involvement of up to 3 or 4 pulmonary lobes with an area less than one-third the volume of each lobe or involvement of one or two lobes with a larger area on CT scan
O2Sat<94%
It is necessary to have all items 1 to 4 and at least one of items 5 and 6
Exclusion criteria:
History of hospitalization because of COVID-19
Participate in any other clinical trial for the treatment of COVID-19
Patients under mechanical ventilation at the baseline
Bradycardia
Sensitivity to Atazanavir
Active cancer
Immune deficiency or immune compromised
Baseline abnormal ECG
Pregnancy and lactation
Renal impairment (CLcr<50 mL/min)
Severe hepatic impairment (Child-pough C)
Multi organ failure
Concomitant use of rifampin, carbamazepine, phenytoin
Age
From 18 years old to 75 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Investigator
Outcome assessor
Sample size
Target sample size:
120
Randomization (investigator's opinion)
Randomized
Randomization description
Before randomization, the effect of confounding factors on the two treatment arms was adjusted. Sealed envelope online software was used to randomize the treatment assignment to the two treatment arms A and B (Keltra/ hydroxychloroquine diet and atazanavir/ritonavir/ hydroxychloroquine diet, respectively) and thus 120 patients were divided into 30 quadri blocks.
Blinding (investigator's opinion)
Double blinded
Blinding description
To eliminate Confounding by indication as well as Confounding by severity, the investigator (clinical pharmacy assistant) and patients will be blind to the type of treatment. The treatment will be assigned in accordance with the above block randomization under the supervision of a physician.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of Mazandaran University of Medical Sciences
Street address
Imam Square, Joybar Three Ways, the beginning of Valiasr Highway, the headquarters of Mazandaran University of Medical Sciences
City
Sari
Province
Mazandaran
Postal code
۴۸۱۵۷۳۳۹۷۱
Approval date
2020-08-12, 1399/05/22
Ethics committee reference number
IR.MAZUMS.REC.1399.602
Health conditions studied
1
Description of health condition studied
Effectiveness and safety of Atazanavir in COVID-19
ICD-10 code
U07.1 COVI
ICD-10 code description
Virus Identified
Primary outcomes
1
Description
Recovery within 10 days of starting medication
Timepoint
daily during 10 days from the beginning of intervention
Method of measurement
Measurement of O2 saturation% by pulse oximeter and clinical signs under the supervision of the physician including (no fever - no dyspnea - no cough or improvement compared to baseline - no fatigue or improvement compared to baseline - oral intake for at least 24 hours)
Secondary outcomes
1
Description
survival rate
Timepoint
daily
Method of measurement
By a designed checklist
2
Description
Recovery within 14 days after starting medication
Timepoint
daily until the day 14 after beginning of intervention
Method of measurement
Measurement of O2 saturation% by pulse oximeter and clinical signs under the supervision of the physician including (no fever - no dyspnea - no cough or improvement compared to baseline - no fatigue or improvement compared to baseline - oral intake for at least 24 hours)
3
Description
Number of days hospitalized
Timepoint
daily
Method of measurement
By a designed checklist
4
Description
number of days in ICU
Timepoint
daily
Method of measurement
By a designed checklist
5
Description
number of days intubated
Timepoint
daily
Method of measurement
By a designed checklist
Intervention groups
1
Description
Intervention group: Hydroxychloroquine 400 mg single dose on the first day with atazanavir/ritonavir 100/300 mg daily (2 serving which one contains placebo) for at least 5 days is administered. Atazanavir Considerations: If the patient is receiving PPIs, an interval of at least 12 hours after PPIs and at least 2 hours after H2 blocker should be considered. Take the medicine after or with a meal. Drug interactions with atazanavir including the concomitant use of statins, CYP3A4 inducers, or inhibitors should be considered to dose adjustment.
Category
Treatment - Drugs
2
Description
Intervention group: Hydroxychloroquine 400 mg single dose on the first day with Kaletra (Lopinavir/Ritonavir) (50/200) 2 tablets every 12 hours for at least 5 days is administered.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Razi hospital
Full name of responsible person
Hamideh Abbaspour kasgari
Street address
Yusef Reza Ave.
City
Qaemshahr
Province
Mazandaran
Postal code
4565686143
Phone
+98 11 4221 8018
Fax
+98 11 4221 8011
Email
razi-ghh@mazums.ac.ir
Web page address
https://razihospital.mazums.ac.ir/
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Research and technology department
Street address
Imam Square, Joybar Three Ways, the beginning of Valiasr Highway, the headquarters of Mazandaran University of Medical Sciences
City
Sari
Province
Mazandaran
Postal code
4815733971
Phone
+98 11 3304 4000
Email
publicrel@mazums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Mazandaran 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
Mazandaran University of Medical Sciences
Full name of responsible person
Hamideh Abbaspour Kasgari
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of pharmacy, Payambar Azam academic complex, 18 km of Khazar Abad Ave, Sari
City
Sari
Province
Mazandaran
Postal code
4763947444
Phone
+98 11 4203 1035
Email
dr.abbaspour1@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Hamideh Abbaspour Kasgari
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of pharmacy, Payambar Azam academic complex, 18 km of Khazar Abad Ave, Sari
City
Sari
Province
Mazandaran
Postal code
4763947444
Phone
+98 11 4203 1035
Email
dr.abbaspour1@yahoo.com
Web page address
Person responsible for updating data
Contact
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Hamideh Abbaspour Kasgari
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of pharmacy, Payambar Azam academic complex, 18 km of Khazar Abad Ave, Sari
City
Sari
Province
Mazandaran
Postal code
4763947444
Phone
+98 11 4203 1035
Email
dr.abbaspour1@yahoo.com
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
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
All collected deidentified IPD
When the data will become available and for how long
Starting 1 month after publication
To whom data/document is available
Researchers working in academic and scientific institutions
Under which criteria data/document could be used
In situations which the researchers have expressed their willing
From where data/document is obtainable
Email address
What processes are involved for a request to access data/document
In a short time after request, will be available with email