Evaluation of safety and efficacy of hydroxychloroquine plus favipiravir drug regimen in comparison with hydroxychloroquine plus kaletra on the need for intensive care unit treatment in patients with COVID-19; a randomized, multicenter, parallel groups, open label study
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General information
2020-04-02, 1399/01/14
2020-04-01, 1399/01/13
2020-04-0201 00:00:00
2020-06-03, 1399/03/14
2020-06-02, 1399/03/13
2020-06-0302 00:00:00
empty
Actual trial started one day earlier and more centers added
Actual trial started one day earlier and more centers added
empty
تاریخ شروع کارآزمایی یک روز زودتر آغاز می شود و تعداد مراکز نیز اضافه شدند
تاریخ شروع کارآزمایی یک روز زودتر آغاز می شود و تعداد مراکز نیز اضافه شدند
In this study, we will use block randomization methods using block size of four. We will use Excel software and rand() function to generate the random sequence. The master randomization list will be kept by the epidemiologist working wit the research team.
In this study, we will use block randomization methods using variable block size of four and six stratified by center. We will use Excel software and rand() function to generate the random sequence. The master randomization list will be kept by the epidemiologist working wit the research team.
In this study, we will use block randomization methods using variable block size of four and six stratified by center. We will use Excel software and rand() function to generate the random sequence. The master randomization list will be kept by the epidemiologist working wit the research team.
در این مطالعه از روش تصادفی سازی بلوکی ( Block Randomization ) با استفاده از بلوک های چهار تایی با ترتیب تصادفی استفاده خواهد شد. از نرم افزار اکسل و فانکشن rand برای تهیه ترتیب های تصادفی بهره خواهیم گرفت. فایل های ایجاد شده در طی پروسه تولید زنجیره تصادفی و نتایج آن نزد اپیدمیولوژیست مطالعه نگهداری خواهد شد.
در این مطالعه از روش تصادفی سازی بلوکی ( Block Randomization ) با استفاده از بلوک های چهار تایی، و شش تایی با ترتیب تصادفی طبقه بندی شده با مرکز استفاده خواهد شد. از نرم افزار اکسل و فانکشن rand برای تهیه ترتیب های تصادفی بهره خواهیم گرفت. فایل های ایجاد شده در طی پروسه تولید زنجیره تصادفی و نتایج آن نزد اپیدمیولوژیست مطالعه نگهداری خواهد شد.
در این مطالعه از روش تصادفی سازی بلوکی ( Block Randomization ) با استفاده از بلوک های چهار تایی، و شش تایی با ترتیب تصادفی طبقه بندی شده با مرکز استفاده خواهد شد. از نرم افزار اکسل و فانکشن rand برای تهیه ترتیب های تصادفی بهره خواهیم گرفت. فایل های ایجاد شده در طی پروسه تولید زنجیره تصادفی و نتایج آن نزد اپیدمیولوژیست مطالعه نگهداری خواهد شد.
Recruitment centers
#1
Name of recruitment center - English: Isfahan Khorshid Hospital
Name of recruitment center - Persian: بیمارستان خورشید اصفهان
Full name of responsible person - English: Dr Ramin Sami
Full name of responsible person - Persian: دکتر رامین سامی
Street address - English: 8 Behehst St, Ostandari St
Street address - Persian: هشت بهشت، خ استانداری
City - English: Isfahan
City - Persian: اصفهان
Province: Isfehan
Country: Iran (Islamic Republic of)
Postal code: 03132222127
Phone: +98 31 3222 2127
Fax:
Email: biganeh75@gmail.com
Web page address:
Name of recruitment center - English: Isfahan Khorshid Hospital Name of recruitment center - Persian: بیمارستان خورشید اصفهان Full name of responsible person - English: Dr Ramin Sami Full name of responsible person - Persian: دکتر رامین سامی Street address - English: 8 Behehst St, Ostandari St Street address - Persian: هشت بهشت، خ استانداری City - English: Isfahan City - Persian: اصفهان Province: Isfehan Country: Iran (Islamic Republic of) Postal code: 03132222127 Phone: +98 31 3222 2127 Fax: Email: biganeh75@gmail.com Web page address:
#2
Name of recruitment center - English: Shahid Beheshti
Name of recruitment center - Persian: بیمارستان شهید بهشتی کاشان
Full name of responsible person - English: Dr Mansooreh Momen Heravi
Full name of responsible person - Persian: دکتر منصوره مومن هروی
Street address - English: Qotb ravandi Bulevard
Street address - Persian: بلوار قطب راوندی
City - English: Isfahan
City - Persian: کاشان
Province: Isfehan
Country: Iran (Islamic Republic of)
Postal code: 8715981151
Phone: +98 31 5554 0026
Fax:
Email: biganeh75@gmail.com
Web page address:
Name of recruitment center - English: Shahid Beheshti Name of recruitment center - Persian: بیمارستان شهید بهشتی کاشان Full name of responsible person - English: Dr Mansooreh Momen Heravi Full name of responsible person - Persian: دکتر منصوره مومن هروی Street address - English: Qotb ravandi Bulevard Street address - Persian: بلوار قطب راوندی City - English: Isfahan City - Persian: کاشان Province: Isfehan Country: Iran (Islamic Republic of) Postal code: 8715981151 Phone: +98 31 5554 0026 Fax: Email: biganeh75@gmail.com Web page address:
#3
Name of recruitment center - English: Kosar Hospital
Name of recruitment center - Persian: بیمارستان کوثر سمنان
Full name of responsible person - English: Dr Mohamad Memarian
Full name of responsible person - Persian: دکتر محمد معماریان
Street address - English: Golestan town
Street address - Persian: شهرک گلستان
City - English: Semnan
City - Persian: سمنان
Province: Semnan
Country: Iran (Islamic Republic of)
Postal code: 3519899951
Phone: +98 23 3142 0023
Fax:
Email: biganeh75@gmail.com
Web page address:
Name of recruitment center - English: Kosar Hospital Name of recruitment center - Persian: بیمارستان کوثر سمنان Full name of responsible person - English: Dr Mohamad Memarian Full name of responsible person - Persian: دکتر محمد معماریان Street address - English: Golestan town Street address - Persian: شهرک گلستان City - English: Semnan City - Persian: سمنان Province: Semnan Country: Iran (Islamic Republic of) Postal code: 3519899951 Phone: +98 23 3142 0023 Fax: Email: biganeh75@gmail.com Web page address:
#4
Name of recruitment center - English: Velaiat Hospital
Name of recruitment center - Persian: بیمارستان ولایت قزوین
Full name of responsible person - English: Dr Mariam Qaraati
Full name of responsible person - Persian: دکتر مریم قرائتی
Street address - English: Taavon Square
Street address - Persian: میدان تعاون
City - English: Qazvin
City - Persian: قزوین
Province: Qazvin
Country: Iran (Islamic Republic of)
Postal code: 02833790610
Phone: +98 28 3379 0627
Fax:
Email: biganeh75@gmail.com
Web page address:
Name of recruitment center - English: Velaiat Hospital Name of recruitment center - Persian: بیمارستان ولایت قزوین Full name of responsible person - English: Dr Mariam Qaraati Full name of responsible person - Persian: دکتر مریم قرائتی Street address - English: Taavon Square Street address - Persian: میدان تعاون City - English: Qazvin City - Persian: قزوین Province: Qazvin Country: Iran (Islamic Republic of) Postal code: 02833790610 Phone: +98 28 3379 0627 Fax: Email: biganeh75@gmail.com Web page address:
#5
Name of recruitment center - English: Emam khomeini Hospital
Name of recruitment center - Persian: بیمارستان امام ساری
Full name of responsible person - English: Dr Roya Qasemian
Full name of responsible person - Persian: دکتر رویا قاسمیان
Street address - English: Imam Square, Vali Asr Highway
Street address - Persian: میدان امام، بزرگراه ولی عصر
City - English: Sari
City - Persian: ساری
Province: Mazandaran
Country: Iran (Islamic Republic of)
Postal code: 01133361700
Phone: +98 11 3336 1700
Fax:
Email: biganeh75@gmail.com
Web page address:
Name of recruitment center - English: Emam khomeini Hospital Name of recruitment center - Persian: بیمارستان امام ساری Full name of responsible person - English: Dr Roya Qasemian Full name of responsible person - Persian: دکتر رویا قاسمیان Street address - English: Imam Square, Vali Asr Highway Street address - Persian: میدان امام، بزرگراه ولی عصر City - English: Sari City - Persian: ساری Province: Mazandaran Country: Iran (Islamic Republic of) Postal code: 01133361700 Phone: +98 11 3336 1700 Fax: Email: biganeh75@gmail.com Web page address:
#6
Name of recruitment center - English: Labafinejad Hospital
Name of recruitment center - Persian: بیمارستان لبافی نژاد تهران
Full name of responsible person - English: Dr Shadi Ziaei
Full name of responsible person - Persian: دکتر شادی ضیایی
Street address - English: Pasdaran St, 9th Bostan St
Street address - Persian: خیابان پاسداران - خیابان بوستان نهم
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 1666663111
Phone: +98 21 2360 1000
Fax:
Email: biganeh75@gmail.com
Web page address:
Name of recruitment center - English: Labafinejad Hospital Name of recruitment center - Persian: بیمارستان لبافی نژاد تهران Full name of responsible person - English: Dr Shadi Ziaei Full name of responsible person - Persian: دکتر شادی ضیایی Street address - English: Pasdaran St, 9th Bostan St Street address - Persian: خیابان پاسداران - خیابان بوستان نهم City - English: Tehran City - Persian: تهران Province: Tehran Country: Iran (Islamic Republic of) Postal code: 1666663111 Phone: +98 21 2360 1000 Fax: Email: biganeh75@gmail.com Web page address:
Protocol summary
Study aim
Comparing safety and efficacy of Favipiravir and Kaletra in COVID-19
Design
Randomized parallel group, clinical trial, open label
Settings and conduct
The design is a multicenter clinical trial that will be conducted in 10 centers all over the country.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Diagnosis of COVID-19 based on either ground glass appearance in chest CT scan or positive RT-PCR test for COVID-19; Requiring hospitalization; Patient's age between 16 and 100 years; Signed informed consent form; Exclusion criteria: Receiving other antiviral medications such as (Kaletra, Ribavirin, Oseltamivir); Chronic liver or renal failure; HIV; GI bleeding; Pregnancy; Lactation; QT interval > 500 ms.
Intervention groups
Intervention group: Group receiving Favipiravir plus Hydroxychloroquine. Stat dose of eight 200 mg Favipiravir tablets (total 1600 mg) followed by Favipiravir 600 mg three times a day for 7 days plus Hydroxychloroquine 200mg two times per day for 7 days. Control group: Group receiving Kaletra plus Hydroxychloroquine regimen. Stat dose of two 200 mg Hydroxychloroquine tablets (total 400 mg) followed by Kaletra(Lopinavir/Ritonavir) 200/50 mg two times a day for 7 days.
Main outcome variables
Admission to intensive care unit, In-hopital mortality, length of stay in hospital, Radiological Treatment Response (CT scan), Laboratory Treatment Response (return of blood cell count and CRP values to normal) Fever, Dyspnea, Oxygen saturation after discontinuation of supplemental oxygen for 5 minutes, Oxygen therapy maximum flow during the day (lit/min), and Adverse and allergic drug reactions
General information
Reason for update
Actual trial started one day earlier and more centers added
Acronym
IRCT registration information
IRCT registration number:IRCT20200318046812N1
Registration date:2020-04-01, 1399/01/13
Registration timing:registered_while_recruiting
Last update:2020-04-01, 1399/01/13
Update count:6
Registration date
2020-04-01, 1399/01/13
Registrant information
Name
Mostafa Ghanei
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8860 0067
Email address
mghaneister@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-04-01, 1399/01/13
Expected recruitment end date
2020-06-02, 1399/03/13
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of safety and efficacy of hydroxychloroquine plus favipiravir drug regimen in comparison with hydroxychloroquine plus kaletra on the need for intensive care unit treatment in patients with COVID-19; a randomized, multicenter, parallel groups, open label study
Public title
Comparison of the safety and efficacy of Favipiravir and kaletra in COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Diagnosis of COVID-19 based on either ground glass appearance in chest CT scan or positive RT-PCR test for COVID-19
Requiring hospitalization because of: Patient's oxygen saturation less than 93% OR
Requiring hospitalization because of: GCS score less than 15 OR
Requiring hospitalization because of: systolic blood pressure less than 100 or 30 mmHg decrease in systolic blood pressure from the level prior to current illness OR
Requiring hospitalization because of: renal failure (creatinine 1.5 times the previous measurement in the last 7 days OR
Requiring hospitalization because of: liver failure (AST and ALT 3 times upper limit of normal)
Patient's age between 16 and 100 years
Signed informed consent form.
Exclusion criteria:
Receiving other antiviral medications such as (Kaletra, Ribavirin, Oseltamivir, ...)
Chronic liver failure
Chronic Renal Failure
Patients with acute problems whose survival is expected to be less than 48 hours
HIV patients
A history of gastrointestinal bleeding
Pregnancy and lactation
QT interval exceeds 500 ms
Age
From 16 years old to 100 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
324
Randomization (investigator's opinion)
Randomized
Randomization description
In this study, we will use block randomization methods using variable block size of four and six stratified by center. We will use Excel software and rand() function to generate the random sequence. The master randomization list will be kept by the epidemiologist working wit the research team.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Iran university of medical sciences
Street address
Iran University of Medical Sciences, Hemmat Highway, Next to Milad Tower, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
۱۴۴۹۶۱۴۵۳۵
Approval date
2020-03-30, 1399/01/11
Ethics committee reference number
IR.IUMS.REC.1399.065
2
Ethics committee
Name of ethics committee
Baqiyatallah university of medical sciences
Street address
Tehran, Vanak Square, Mulla Sadra Street
City
Tehran
Province
Tehran
Postal code
1435916471
Approval date
2020-03-26, 1399/01/07
Ethics committee reference number
IR.BMSU.REC.1399.017
Health conditions studied
1
Description of health condition studied
COVID-19
ICD-10 code
COVID-19
ICD-10 code description
U07.1 COVID-19
Primary outcomes
1
Description
Admission to intensive care unit
Timepoint
Once (when admitted to intensive care unit)
Method of measurement
Hospital records
Secondary outcomes
1
Description
In-hopital mortality
Timepoint
once
Method of measurement
Patient medical records
2
Description
length of stay in hospital
Timepoint
Once at discharge
Method of measurement
Patient medical records
3
Description
Radiological Treatment Response (CT scan) , more than 50% reduction in the affected area
Timepoint
CT scan will be done twice (once at the time of admission and the second time 10 days after discharge). Assessment will be done comparing the second CT with the first one
Method of measurement
Patient CT scan
4
Description
Laboratory Treatment Response; return of blood cell count and CRP values to normal
Timepoint
Daily
Method of measurement
Laboratory kits
5
Description
Fever
Timepoint
Daily
Method of measurement
Patient medical records
6
Description
Dyspnea
Timepoint
Daily
Method of measurement
Patient medical records
7
Description
Oxygen saturation without supplemental oxygen. Measurement will be done after discontinuation of oxygen therapy for 5 minutes.
Timepoint
4 times a day while in the wards
Method of measurement
Observation
8
Description
Oxygen therapy maximum flow during the day (lit/min)
Timepoint
Daily
Method of measurement
Patient medical records
9
Description
Allergic drug reaction
Timepoint
Daily
Method of measurement
Adverse Drug Reaction forms
10
Description
Adverse drug reactions
Timepoint
Daily
Method of measurement
Adverse Drug Reaction forms
Intervention groups
1
Description
Intervention group: Group receiving Favipiravir plus Hydroxychloroquine. Stat dose of eight 200 mg Favipiravir tablets (total 1600 mg) followed by Favipiravir 600 mg three times a day for 7 days plus Hydroxychloroquine 200mg two times per day for 7 days. This regimen could be continued for 10 days if necessary according to clinical response of the patient. Other supportive and routine care will be the same in both groups.
Category
Treatment - Drugs
2
Description
Control group: Group receiving Kaletra plus Hydroxychloroquine regimen. Stat dose of two 200 mg Hydroxychloroquine tablets (total 400 mg) followed by Kaletra(Lopinavir/Ritonavir) 200/50 mg two times a day for 7 days. This regimen could be continued for 10 days if necessary according to clinical response of the patient. Other supportive and routine care will be the same in both groups.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Baqiyatallah university of medical sciences
Full name of responsible person
Dr Behzad Einollahi
Street address
Tehran, Vanak Square, Mulla Sadra Street, Sheikh Bahai Street