Back to resultsClinical Trial For Early SARS-CoV-2 (COVID-19) Treatment
Primary Purpose
Covid19
Status
Completed
Phase
Phase 3
Locations
Turkey
Study Type
Interventional
Intervention
Hydroxychloroquine
Favipiravir
Favipiravir + Hydroxychloroquine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring COVID-19, Hydroxychloroquine, Favipiravir
Eligibility Criteria
Inclusion Criteria:
- Volunteers who have understood all the procedures to be applied within the scope of the study protocol and gave their consent.
- Patients between 18-60 years old.
- Patients whose symptoms and complaints associated with COVID-19 started within 48 hours.
Mild cases whose treatment to be given as outpatient.
- Although asymptomatic, patients with high CRP (> 20 mg/L) and/or lymphopenia (<1000/mm3)
- Patients with symptoms such as fever, muscle/joint pain, cough, sore throat, nasal congestion, loss of smell.
- Patients without serious underlying diseases (cardiovascular diseases, diabetes mellitus, hypertension, cancer, chronic lung diseases, immunosuppressive conditions)
- Patients with normal chest x-ray and / or chest tomography (no sign of pneumonia)
- Patients who accept oropharyngeal sample and venous blood collection at regular intervals within the scope of the protocol.
- Patients who were not involved in any other interventional study.
Exclusion Criteria:
- Patients who do not give their consent in writing after informing.
- Being under the age of 18 and over the age of 60.
- Patients with a known history of allergy to one of the study drugs (hydroxychloroquine, favipiravir).
- Volunteers who the researcher thinks may have problems with adherence to treatment.
- Volunteers who will have trouble taking medication by mouth due to resistant nausea, vomiting or chronic diarrhea.
- Patients with chronic liver disease and transaminase (ALT or AST) levels 5 times the higher than the normal level.
- Patients with heart disease or arrhythmia history.
- Patients with gout or hyperuricemia.
- Patients with signs of pneumonia in their lungs.
- Patients with chronic renal failure (glomerular filtration rate <30).
- Pregnant or breastfeeding patients.
Sites / Locations
- Ankara City Hospital
- Başakşehir Çam ve Sakura City Hospital
- Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital
- Istanbul University Istanbul Medicine Faculty
- Kartal Dr. Lütfi Kırdar City Hospital
- Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Hydroxychloroquine + Favipiravir
Favipiravir + Placebo (Hydroxychloroquine)
Hydroxychloroquine + Placebo (Favipiravir)
Placebo (Favipiravir) + Placebo (Hydroxychloroquine)
Arm Description
Hydroxychloroquine 2x200 mg 5 days and favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days)
Favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine ) 2x200 mg (5 days)
Hydroxychloroquine 2x200 mg (for 5 days) + placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days)
Placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine) 2x200 mg (5 days)
Outcomes
Primary Outcome Measures
Worsening of clinical findings
Worsening of clinical findings such as respiratory distress or persistence of fever, which require hospital admission to begin another treatment (for example, remdesivir, dexamethasone, anti-cytokines, etc.)
Secondary Outcome Measures
Complete resolution of symptoms and signs
Complete resolution of symptoms and signs
Complete resolution of symptoms and signs
Complete resolution of symptoms and signs
Negative RT-PCR test for SARS-CoV-2
Negative RT-PCR test for SARS-CoV-2 virus
Determination of IgM, IgG levels for SARS-CoV-2
Determination of IgM, IgG levels for SARS-CoV-2 virus
Negative RT-PCR test for SARS-CoV-2
Negative RT-PCR test for SARS-CoV-2 on the 30th day visit
Determination of IgM, IgG antibodies
Determination of IgM, IgG antibodies against SARS-CoV-2
Development of signs of pneumonia
Development of signs of pneumonia
Requirement of respiratory support with oxygen mask
Requirement of respiratory support with oxygen mask
Requirement of respiratory support with high flow oxygen
Requirement of respiratory support with high flow oxygen
Requirement of mechanical ventilation
Requirement of mechanical ventilation
Death
Death
The rate of discontinuation of treatments due to side effects
The rate of discontinuation of treatments due to side effects (gastrointestinal, allergic skin rash, arrhythmia, other cardiac reasons)
Time to improvement of symptoms after the initiation of study drugs
Time to improvement of symptoms after the initiation of study drugs
Full Information
NCT ID
NCT04981379
First Posted
July 26, 2021
Last Updated
July 26, 2021
Sponsor
Health Institutes of Turkey
1. Study Identification
Unique Protocol Identification Number
NCT04981379
Brief Title
Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment
Official Title
Efficacy and Safety of the Use of Hydroxychloroquine, Favipiravir or Hydroxychloroquine + Favipiravir in Early SARS-CoV-2 (COVID-19) Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
November 16, 2020 (Actual)
Primary Completion Date
January 31, 2021 (Actual)
Study Completion Date
February 16, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Health Institutes of Turkey
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a randomized, double-blinded, and placebo controlled phase III clinical trial which aims to investigate the superiority of hydroxychloroquine, favipiravir or hydroxychloroquine + favipiravir treatment, initiated especially in the early period in the treatment of COVID-19, over the patients being followed up with placebo in adults aged 18~59 Years.
Detailed Description
This study is a randomized, double-blinded, and placebo controlled phase III clinical trial in in adults aged 18~59 Years. The study was planned as a multicenter, randomized controlled, double-blind, parallel-arm drug study. The purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine, favipiravir, or hydroxychloroquine + favipiravir treatments that were initiated early in patients who were caught during filiation or who were decided to be outpatient due to mild disease findings during hospital admission, after the diagnosis of COVID-19 against patients with placebo. It is planned that the study will be conducted with two separate arms. Study arms are planned as 2:2:2:1 for 320:320:320:160 patients as follows. The dose of Favipiravir has been determined as the standard dose. Hydroxychloroquine will also be given without a loading dose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
COVID-19, Hydroxychloroquine, Favipiravir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double-Blind
Allocation
Randomized
Enrollment
1120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hydroxychloroquine + Favipiravir
Arm Type
Active Comparator
Arm Description
Hydroxychloroquine 2x200 mg 5 days and favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days)
Arm Title
Favipiravir + Placebo (Hydroxychloroquine)
Arm Type
Active Comparator
Arm Description
Favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine ) 2x200 mg (5 days)
Arm Title
Hydroxychloroquine + Placebo (Favipiravir)
Arm Type
Active Comparator
Arm Description
Hydroxychloroquine 2x200 mg (for 5 days) + placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days)
Arm Title
Placebo (Favipiravir) + Placebo (Hydroxychloroquine)
Arm Type
Placebo Comparator
Arm Description
Placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine) 2x200 mg (5 days)
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Hydroxychloroquine sulfate
Intervention Description
Hydroxychloroquine (200 mg), as two tablets per day for 5-day interval + Placebo [Favipiravir (1600 mg)], as two tablet per day at the first day and then Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval.
Intervention Type
Drug
Intervention Name(s)
Favipiravir
Other Intervention Name(s)
Favicovir Film Tablet
Intervention Description
Favipiravir (1600 mg), as two tablet per day at the first day and then Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval + Placebo [Hydroxychloroquine (200 mg)], as two tablets per day for 5-day interval.
Intervention Type
Drug
Intervention Name(s)
Favipiravir + Hydroxychloroquine
Other Intervention Name(s)
Favicovir Film Tablet + Hydroxychloroquine sulfate
Intervention Description
Favipiravir (1600 mg), as two tablet per day at the first day and then Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval + Hydroxychloroquine (200 mg), as two tablets per day for 5-day interval.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo [Favipiravir (1600 mg)], as two tablet per day at the first day and then Placebo Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval + Hydroxychloroquine (200 mg), as two tablets per day for 5-day interval.
Primary Outcome Measure Information:
Title
Worsening of clinical findings
Description
Worsening of clinical findings such as respiratory distress or persistence of fever, which require hospital admission to begin another treatment (for example, remdesivir, dexamethasone, anti-cytokines, etc.)
Time Frame
During the study
Secondary Outcome Measure Information:
Title
Complete resolution of symptoms and signs
Description
Complete resolution of symptoms and signs
Time Frame
Fifth day after examination
Title
Complete resolution of symptoms and signs
Description
Complete resolution of symptoms and signs
Time Frame
Tenth day after examination
Title
Negative RT-PCR test for SARS-CoV-2
Description
Negative RT-PCR test for SARS-CoV-2 virus
Time Frame
Tenth day after examination
Title
Determination of IgM, IgG levels for SARS-CoV-2
Description
Determination of IgM, IgG levels for SARS-CoV-2 virus
Time Frame
Tenth day after examination
Title
Negative RT-PCR test for SARS-CoV-2
Description
Negative RT-PCR test for SARS-CoV-2 on the 30th day visit
Time Frame
Thirtieth day after examination
Title
Determination of IgM, IgG antibodies
Description
Determination of IgM, IgG antibodies against SARS-CoV-2
Time Frame
Thirtieth day after examination
Title
Development of signs of pneumonia
Description
Development of signs of pneumonia
Time Frame
During the study
Title
Requirement of respiratory support with oxygen mask
Description
Requirement of respiratory support with oxygen mask
Time Frame
During the study
Title
Requirement of respiratory support with high flow oxygen
Description
Requirement of respiratory support with high flow oxygen
Time Frame
During the study
Title
Requirement of mechanical ventilation
Description
Requirement of mechanical ventilation
Time Frame
During the study
Title
Death
Description
Death
Time Frame
During the study
Title
The rate of discontinuation of treatments due to side effects
Description
The rate of discontinuation of treatments due to side effects (gastrointestinal, allergic skin rash, arrhythmia, other cardiac reasons)
Time Frame
During the study
Title
Time to improvement of symptoms after the initiation of study drugs
Description
Time to improvement of symptoms after the initiation of study drugs
Time Frame
During the study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Volunteers who have understood all the procedures to be applied within the scope of the study protocol and gave their consent.
Patients between 18-60 years old.
Patients whose symptoms and complaints associated with COVID-19 started within 48 hours.
Mild cases whose treatment to be given as outpatient.
Although asymptomatic, patients with high CRP (> 20 mg/L) and/or lymphopenia (<1000/mm3)
Patients with symptoms such as fever, muscle/joint pain, cough, sore throat, nasal congestion, loss of smell.
Patients without serious underlying diseases (cardiovascular diseases, diabetes mellitus, hypertension, cancer, chronic lung diseases, immunosuppressive conditions)
Patients with normal chest x-ray and / or chest tomography (no sign of pneumonia)
Patients who accept oropharyngeal sample and venous blood collection at regular intervals within the scope of the protocol.
Patients who were not involved in any other interventional study.
Exclusion Criteria:
Patients who do not give their consent in writing after informing.
Being under the age of 18 and over the age of 60.
Patients with a known history of allergy to one of the study drugs (hydroxychloroquine, favipiravir).
Volunteers who the researcher thinks may have problems with adherence to treatment.
Volunteers who will have trouble taking medication by mouth due to resistant nausea, vomiting or chronic diarrhea.
Patients with chronic liver disease and transaminase (ALT or AST) levels 5 times the higher than the normal level.
Patients with heart disease or arrhythmia history.
Patients with gout or hyperuricemia.
Patients with signs of pneumonia in their lungs.
Patients with chronic renal failure (glomerular filtration rate <30).
Pregnant or breastfeeding patients.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmet Gül, Prof.
Organizational Affiliation
Faculty Member
Official's Role
Study Director
Facility Information:
Facility Name
Ankara City Hospital
City
Ankara
Country
Turkey
Facility Name
Başakşehir Çam ve Sakura City Hospital
City
Istanbul
Country
Turkey
Facility Name
Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital
City
Istanbul
Country
Turkey
Facility Name
Istanbul University Istanbul Medicine Faculty
City
Istanbul
Country
Turkey
Facility Name
Kartal Dr. Lütfi Kırdar City Hospital
City
Istanbul
Country
Turkey
Facility Name
Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital
City
Istanbul
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32967849
Citation
McCullough PA. Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV-2 Infection (COVID-19). Antimicrob Agents Chemother. 2020 Nov 17;64(12):e02017-20. doi: 10.1128/AAC.02017-20. Print 2020 Nov 17.
Results Reference
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PubMed Identifier
32972430
Citation
Shrestha DB, Budhathoki P, Khadka S, Shah PB, Pokharel N, Rashmi P. Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis. Virol J. 2020 Sep 24;17(1):141. doi: 10.1186/s12985-020-01412-z.
Results Reference
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PubMed Identifier
32958718
Citation
Doi Y, Hibino M, Hase R, Yamamoto M, Kasamatsu Y, Hirose M, Mutoh Y, Homma Y, Terada M, Ogawa T, Kashizaki F, Yokoyama T, Koba H, Kasahara H, Yokota K, Kato H, Yoshida J, Kita T, Kato Y, Kamio T, Kodama N, Uchida Y, Ikeda N, Shinoda M, Nakagawa A, Nakatsumi H, Horiguchi T, Iwata M, Matsuyama A, Banno S, Koseki T, Teramachi M, Miyata M, Tajima S, Maeki T, Nakayama E, Taniguchi S, Lim CK, Saijo M, Imai T, Yoshida H, Kabata D, Shintani A, Yuzawa Y, Kondo M. A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01897-20. doi: 10.1128/AAC.01897-20. Print 2020 Nov 17.
Results Reference
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PubMed Identifier
32203437
Citation
Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol. 2020 Apr;15(4):247-249. doi: 10.1038/s41565-020-0674-9.
Results Reference
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PubMed Identifier
32492293
Citation
Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, Skipper CP, Nascene AA, Nicol MR, Abassi M, Engen NW, Cheng MP, LaBar D, Lother SA, MacKenzie LJ, Drobot G, Marten N, Zarychanski R, Kelly LE, Schwartz IS, McDonald EG, Rajasingham R, Lee TC, Hullsiek KH. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020 Aug 6;383(6):517-525. doi: 10.1056/NEJMoa2016638. Epub 2020 Jun 3.
Results Reference
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PubMed Identifier
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Citation
Kaptein SJF, Jacobs S, Langendries L, Seldeslachts L, Ter Horst S, Liesenborghs L, Hens B, Vergote V, Heylen E, Barthelemy K, Maas E, De Keyzer C, Bervoets L, Rymenants J, Van Buyten T, Zhang X, Abdelnabi R, Pang J, Williams R, Thibaut HJ, Dallmeier K, Boudewijns R, Wouters J, Augustijns P, Verougstraete N, Cawthorne C, Breuer J, Solas C, Weynand B, Annaert P, Spriet I, Vande Velde G, Neyts J, Rocha-Pereira J, Delang L. Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity. Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):26955-26965. doi: 10.1073/pnas.2014441117. Epub 2020 Oct 9.
Results Reference
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Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment
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