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

NCT04981379 | Completed Phase 3 DMC

• 1 other identifier: COVID-19-FAV-HQ
• Study Type: interventional
• Target: 1,120
• Locations: 1 country
• Sites: 6

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.

Conditions

Covid19

Keywords

COVID-19; Hydroxychloroquine; Favipiravir

Outcome Measures

Primary Outcomes (1)

• 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.)

  During the study

Secondary Outcomes (13)

• Complete resolution of symptoms and signs

  Fifth day after examination

• Complete resolution of symptoms and signs

  Tenth day after examination

• Negative RT-PCR test for SARS-CoV-2

  Tenth day after examination

• Determination of IgM, IgG levels for SARS-CoV-2

  Tenth day after examination

• Negative RT-PCR test for SARS-CoV-2

  Thirtieth day after examination

Study Arms (4)

Hydroxychloroquine + Favipiravir

ACTIVE COMPARATOR

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 + Placebo (Hydroxychloroquine)

ACTIVE COMPARATOR

Favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine ) 2x200 mg (5 days)

Drug: Favipiravir

Hydroxychloroquine + Placebo (Favipiravir)

ACTIVE COMPARATOR

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

Placebo (Favipiravir) + Placebo (Hydroxychloroquine)

PLACEBO COMPARATOR

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

Interventions

Hydroxychloroquine 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.

Also known as: Hydroxychloroquine sulfate

Hydroxychloroquine + Placebo (Favipiravir)

Favipiravir 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.

Also known as: Favicovir Film Tablet

Favipiravir + Placebo (Hydroxychloroquine)

Favipiravir + Hydroxychloroquine 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.

Also known as: Favicovir Film Tablet + Hydroxychloroquine sulfate

Hydroxychloroquine + Favipiravir

Placebo 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.

Placebo (Favipiravir) + Placebo (Hydroxychloroquine)

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Health Institutes of Turkey: lead

Study Sites (6)

Ankara City Hospital

Ankara, Turkey (Türkiye)

Location

Başakşehir Çam ve Sakura City Hospital

Istanbul, Turkey (Türkiye)

Location

Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital

Istanbul, Turkey (Türkiye)

Location

Istanbul University Istanbul Medicine Faculty

Istanbul, Turkey (Türkiye)

Location

Kartal Dr. Lütfi Kırdar City Hospital

Istanbul, Turkey (Türkiye)

Location

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

Istanbul, Turkey (Türkiye)

Location

Related Publications (6)

• 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.

  PMID: 32967849 BACKGROUND

• 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.

  PMID: 32972430 BACKGROUND

• 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.

  PMID: 32958718 BACKGROUND

• 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.

  PMID: 32203437 BACKGROUND

• 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.

  PMID: 32492293 BACKGROUND

• 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.

  PMID: 33037151 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Hydroxychloroquine; favipiravir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ahmet Gül, Prof.

  Faculty Member

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: July 29, 2021
• Study Start: November 16, 2020
• Primary Completion: January 31, 2021
• Study Completion: February 16, 2021
• Last Updated: July 29, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

TU (6)