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

Phase 3

Completed

• Conditions: Covid19
• Interventions: Drug: Favipiravir + Hydroxychloroquine; Drug: Hydroxychloroquine; Drug: Placebo; Drug: Favipiravir

• Registration Number: NCT04981379
• Lead Sponsor: Health Institutes of Turkey

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.

Study Timeline

• Study Start: 2020-11-16
• Primary Completion: 2021-01-31
• Study Completion: 2021-02-16
• Status Verified: 2021-06
• Study First Submitted: 2021-07-26
• Study First Submitted QC: 2021-07-26
• Last Update Submitted: 2021-07-26
• Study First Posted: 2021-07-29
• Last Update Posted: 2021-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydroxychloroquine + Favipiravir	Favipiravir + Hydroxychloroquine	Hydroxychloroquine 2x200 mg 5 days and favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days)
Hydroxychloroquine + Placebo (Favipiravir)	Hydroxychloroquine	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) + Placebo (Hydroxychloroquine)	Placebo	Placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine) 2x200 mg (5 days)
Favipiravir + Placebo (Hydroxychloroquine)	Favipiravir	Favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine ) 2x200 mg (5 days)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Determination of IgM, IgG antibodies	Thirtieth day after examination	Determination of IgM, IgG antibodies against SARS-CoV-2
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)
Complete resolution of symptoms and signs	Tenth day after examination	Complete resolution of symptoms and signs
Determination of IgM, IgG levels for SARS-CoV-2	Tenth day after examination	Determination of IgM, IgG levels for SARS-CoV-2 virus
Development of signs of pneumonia	During the study	Development of signs of pneumonia
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
Requirement of respiratory support with oxygen mask	During the study	Requirement of respiratory support with oxygen mask
Death	During the study	Death
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
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

Trial Locations

Locations (6)

Ankara City Hospital; 🇹🇷 Ankara, Turkey

Istanbul University Istanbul Medicine Faculty; 🇹🇷 Istanbul, Turkey

Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Başakşehir Çam ve Sakura City Hospital; 🇹🇷 Istanbul, Turkey

Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Kartal Dr. Lütfi Kırdar City Hospital; 🇹🇷 Istanbul, Turkey