Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Hydroxychloroquine + Favipiravir Hydroxychloroquine 2x200 mg 5 days and favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) |
Drug: Favipiravir + Hydroxychloroquine
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.
Other Names:
|
| Active Comparator: Favipiravir + Placebo (Hydroxychloroquine) Favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine ) 2x200 mg (5 days) |
Drug: Favipiravir
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.
Other Names:
|
| Active Comparator: Hydroxychloroquine + Placebo (Favipiravir) Hydroxychloroquine 2x200 mg (for 5 days) + placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) |
Drug: Hydroxychloroquine
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.
Other Names:
|
| Placebo Comparator: Placebo (Favipiravir) + Placebo (Hydroxychloroquine) Placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine) 2x200 mg (5 days) |
Drug: Placebo
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.
|
Outcome Measures
Primary Outcome Measures
- Worsening of clinical findings [During the study]
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 [Fifth day after examination]
Complete resolution of symptoms and signs
- Complete resolution of symptoms and signs [Tenth day after examination]
Complete resolution of symptoms and signs
- Negative RT-PCR test for SARS-CoV-2 [Tenth day after examination]
Negative RT-PCR test for SARS-CoV-2 virus
- Determination of IgM, IgG levels for SARS-CoV-2 [Tenth day after examination]
Determination of IgM, IgG levels for SARS-CoV-2 virus
- Negative RT-PCR test for SARS-CoV-2 [Thirtieth day after examination]
Negative RT-PCR test for SARS-CoV-2 on the 30th day visit
- Determination of IgM, IgG antibodies [Thirtieth day after examination]
Determination of IgM, IgG antibodies against SARS-CoV-2
- Development of signs of pneumonia [During the study]
Development of signs of pneumonia
- Requirement of respiratory support with oxygen mask [During the study]
Requirement of respiratory support with oxygen mask
- Requirement of respiratory support with high flow oxygen [During the study]
Requirement of respiratory support with high flow oxygen
- Requirement of mechanical ventilation [During the study]
Requirement of mechanical ventilation
- Death [During the study]
Death
- The rate of discontinuation of treatments due to side effects [During the study]
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 [During the study]
Time to improvement of symptoms after the initiation of study drugs
Eligibility Criteria
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.
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Patients without serious underlying diseases (cardiovascular diseases, diabetes mellitus, hypertension, cancer, chronic lung diseases, immunosuppressive conditions)
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Patients with normal chest x-ray and / or chest tomography (no sign of pneumonia)
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Patients who accept oropharyngeal sample and venous blood collection at regular intervals within the scope of the protocol.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ankara City Hospital | Ankara | Turkey | ||
| 2 | Başakşehir Çam ve Sakura City Hospital | Istanbul | Turkey | ||
| 3 | Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital | Istanbul | Turkey | ||
| 4 | Istanbul University Istanbul Medicine Faculty | Istanbul | Turkey | ||
| 5 | Kartal Dr. Lütfi Kırdar City Hospital | Istanbul | Turkey | ||
| 6 | Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital | Istanbul | Turkey |
Sponsors and Collaborators
- Health Institutes of Turkey
Investigators
- Study Director: Ahmet Gül, Prof., Faculty Member
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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). pii: e01897-20. doi: 10.1128/AAC.01897-20. Print 2020 Nov 17.
- 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.
- 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.
- 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). pii: e02017-20. doi: 10.1128/AAC.02017-20. Print 2020 Nov 17.
- 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.
- COVID-19-FAV-HQ