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

Covid19 Clinical Trial

Official title:

Efficacy and Safety of the Use of Hydroxychloroquine, Favipiravir or Hydroxychloroquine + Favipiravir in Early SARS-CoV-2 (COVID-19) Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04981379
• Other study ID #: COVID-19-FAV-HQ
• Status: Completed
• Phase: Phase 3
• Start date: November 16, 2020
• Est. completion date: February 16, 2021

Study information

• Verified date: June 2021
• Source: Health Institutes of Turkey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1120
• Est. completion date: February 16, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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.

Related Conditions & MeSH terms

• Covid19

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Turkey	Ankara City Hospital	Ankara
Turkey	Basaksehir Çam ve Sakura City Hospital	Istanbul
Turkey	Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital	Istanbul
Turkey	Istanbul University Istanbul Medicine Faculty	Istanbul
Turkey	Kartal Dr. Lütfi Kirdar City Hospital	Istanbul
Turkey	Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Health Institutes of Turkey

Country where clinical trial is conducted

Turkey, 

References & Publications (6)

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. — View 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). pii: e01897-20. doi: 10.1128/AAC.01897-20. Print 2020 Nov 17. — View 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. — View 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. — View 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). pii: e02017-20. doi: 10.1128/AAC.02017-20. Print 2020 Nov 17. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete resolution of symptoms and signs	Complete resolution of symptoms and signs	Fifth day after examination
Secondary	Complete resolution of symptoms and signs	Complete resolution of symptoms and signs	Tenth day after examination
Secondary	Negative RT-PCR test for SARS-CoV-2	Negative RT-PCR test for SARS-CoV-2 virus	Tenth day after examination
Secondary	Determination of IgM, IgG levels for SARS-CoV-2	Determination of IgM, IgG levels for SARS-CoV-2 virus	Tenth day after examination
Secondary	Negative RT-PCR test for SARS-CoV-2	Negative RT-PCR test for SARS-CoV-2 on the 30th day visit	Thirtieth day after examination
Secondary	Determination of IgM, IgG antibodies	Determination of IgM, IgG antibodies against SARS-CoV-2	Thirtieth day after examination
Secondary	Development of signs of pneumonia	Development of signs of pneumonia	During the study
Secondary	Requirement of respiratory support with oxygen mask	Requirement of respiratory support with oxygen mask	During the study
Secondary	Requirement of respiratory support with high flow oxygen	Requirement of respiratory support with high flow oxygen	During the study
Secondary	Requirement of mechanical ventilation	Requirement of mechanical ventilation	During the study
Secondary	Death	Death	During the study
Secondary	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)	During the study
Secondary	Time to improvement of symptoms after the initiation of study drugs	Time to improvement of symptoms after the initiation of study drugs	During the study