Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment

NCT ID: NCT04981379

Last Updated: 2021-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-16

Study Completion Date

2021-02-16

Brief Summary

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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

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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.

Conditions

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Covid19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double-Blind

Study Groups

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Hydroxychloroquine + Favipiravir

Hydroxychloroquine 2x200 mg 5 days and favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days)

Group Type ACTIVE_COMPARATOR

Favipiravir + Hydroxychloroquine

Intervention Type DRUG

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.

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)

Group Type ACTIVE_COMPARATOR

Favipiravir

Intervention Type DRUG

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.

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)

Group Type ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type DRUG

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.

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)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Hydroxychloroquine sulfate Favicovir Film Tablet Favicovir Film Tablet + Hydroxychloroquine sulfate

Eligibility Criteria

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Inclusion Criteria

1. Volunteers who have understood all the procedures to be applied within the scope of the study protocol and gave their consent.
2. Patients between 18-60 years old.
3. Patients whose symptoms and complaints associated with COVID-19 started within 48 hours.
4. Mild cases whose treatment to be given as outpatient.

1. Although asymptomatic, patients with high CRP (\> 20 mg/L) and/or lymphopenia (\<1000/mm3)
2. Patients with symptoms such as fever, muscle/joint pain, cough, sore throat, nasal congestion, loss of smell.
3. Patients without serious underlying diseases (cardiovascular diseases, diabetes mellitus, hypertension, cancer, chronic lung diseases, immunosuppressive conditions)
4. Patients with normal chest x-ray and / or chest tomography (no sign of pneumonia)
5. Patients who accept oropharyngeal sample and venous blood collection at regular intervals within the scope of the protocol.
6. Patients who were not involved in any other interventional study.

Exclusion Criteria

1. Patients who do not give their consent in writing after informing.
2. Being under the age of 18 and over the age of 60.
3. Patients with a known history of allergy to one of the study drugs (hydroxychloroquine, favipiravir).
4. Volunteers who the researcher thinks may have problems with adherence to treatment.
5. Volunteers who will have trouble taking medication by mouth due to resistant nausea, vomiting or chronic diarrhea.
6. Patients with chronic liver disease and transaminase (ALT or AST) levels 5 times the higher than the normal level.
7. Patients with heart disease or arrhythmia history.
8. Patients with gout or hyperuricemia.
9. Patients with signs of pneumonia in their lungs.
10. Patients with chronic renal failure (glomerular filtration rate \<30).
11. Pregnant or breastfeeding patients.
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Health Institutes of Turkey

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ahmet Gül, Prof.

Role: STUDY_DIRECTOR

Faculty Member

Locations

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Ankara City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Başakşehir Çam ve Sakura City Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Istanbul University Istanbul Medicine Faculty

Istanbul, , Turkey (Türkiye)

Site Status

Kartal Dr. Lütfi Kırdar City Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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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.

Reference Type BACKGROUND
PMID: 32967849 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32972430 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32958718 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32203437 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32492293 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33037151 (View on PubMed)

Other Identifiers

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COVID-19-FAV-HQ

Identifier Type: -

Identifier Source: org_study_id

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