Study on Safety and Efficacy of Favipiravir (Favipira) for COVID-19 Patient in Selected Hospitals of Bangladesh

NCT04402203 | Unknown Phase 2 DMC

• 1 other identifier: 29318042020
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

A recent outbreak of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in Wuhan, China, at the end of 2019. The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnea, and pneumonia. As of 25 February 2020, at least 77 785 cases and 2666 deaths had been identified across China and in other countries; in particular, 977 and 861 cases were identified in South Korea and Japan, respectively. The outbreak has already caused global alarm. On 30 January 2020, the World Health Organization (WHO) declared that the outbreak of SARS-CoV-2 constituted a Public Health Emergency of International Concern (PHEIC), and issued advice in the form of temporary recommendations under the International Health Regulations (IHR).It has been revealed that SARS-CoV-2 has a genome sequence that is 75%-80% identical to that of SARS-CoV, and has more similarities to several bat coronaviruses. SARS-CoV-2 is the seventh reported human-infecting member of the family Coronaviridae, which also includes SARS-CoV and the Middle East respiratory syndrome (MERS)-CoV. It has been identified as the causative agent of COVID-19. Both the clinical and the epidemiological features of COVID-19 patients demonstrate that SARS-CoV-2 infection can lead to intensive care unit (ICU) admission and high mortality. About 16%-21% of people with the virus in China have become severely ill, with a 2%-3% mortality rate. However, there is no specific treatment against the new virus. Therefore, it is urgently necessary to identify effective antiviral agents to combat the disease and explore the clinical effect of antiviral drugs. One efficient approach to discover effective drugs is to test whether the existing antiviral drugs are effective in treating other related viral infections. Several drugs, such as ribavirin, interferon (IFN), Favipiravir (FPV), and Lopinavir (LPV)/ritonavir (RTV), have been used in patients with SARS or MERS, although the efficacy of some drugs remains controversial. It has recently been demonstrated that, as a prodrug, Favipiravir (half maximal effective concentration (EC50) = 61.88 μmol·L-1, half-maximal cytotoxic concentration (CC50) \> 400 μmol·L-1, selectivity index (SI) \> 6.46) effectively inhibits the SARS-CoV-2 infection in Vero E6 cells (ATCC-1586). Furthermore, other reports show that FPV is effective in protecting mice against Ebola virus challenge, although its EC50 value in Vero E6 cells was as high as 67 μmol·L-1. Therefore, clinical studies are urgently needed to evaluate the efficacy and safety of this antiviral nucleoside for COVID-19 treatment. After enrollment of the patients (day 1) depending on inclusion and exclusion criteria and laboratory findings confirming the presence of the COVID-19 virus, 25 patients will receive Favipiravir plus standard treatment and the second group of 25 patients will receive standard treatment only. The comparison of the findings of the follow up studies on days 4, 7, and 10 in terms of clinical manifestations, chest X-ray and laboratory findings, such as Real Time Polymerase Chain Reaction (RT-PCR) results for viral presence will determine whether Favipiravir has safety and efficacy against COVID-19 infections. All ethical issues related to this trial including right of the participants to withdraw from the study should be maintained according to of guidelines of International Conference on Harmonisation (ICH)-Good Clinical Practice (GCP).

Conditions

COVID-19; Favipiravir (Favipira)

Outcome Measures

Primary Outcomes (2)

• Number of participants negative by RT-PCR for the virus at 4-10 days after initiation of therapy.

  Negative by RT-PCR for the virus at 4-10 days after initiation of therapy. However, negative results for the viral presence should be with an interval of at least 24 hours.

  at 4 to 10 days of therapy

• Number of participants with lung condition change assessed with X-ray.

  X-ray findings of lung condition improvement at Day-4, Day-7 and Day-10 of therapy

  at Day-4, Day-7 and Day-10 of therapy

Secondary Outcomes (4)

• Number of participants with clinical recovery

  at Day-4, Day-7 and Day-10 of therapy

• Number of participants with adverse effects of drug.

  at Day-4, Day-7 and Day-10 of therapy

• Number of participants requiring ICU admission

  at Day-4, Day-7 and Day-10 of therapy

• Number of death

  at Day-4, Day-7 and Day-10 of therapy

Study Arms (2)

Favipiravir + Standard Treatment

EXPERIMENTAL

Favipiravir 200 mg (Favipira) tablet will be given orally. Day 1: Tablet Favipiravir 1600 mg twice daily Days 2-Days 10: Tablet Favipiravir 600 mg twice daily.

Drug: Favipiravir

Only Standard Treatment

PLACEBO COMPARATOR

Standard treatment included oxygen inhalation, oral or intravenous rehydration, electrolyte correction, antipyretics, analgesics, antibiotics and antiemetic drugs \& the medication any patient is on due to any concomitant diseases.

Drug: Only Standard Treatment

Interventions

Favipiravir DRUG

Favipiravir 200 mg (Favipira) tablet will be given orally. Day 1: Tablet Favipiravir 1600 mg twice daily Days 2-Days 10: Tablet Favipiravir 600 mg twice daily.

Favipiravir + Standard Treatment

Only Standard Treatment DRUG

Standard treatment included oxygen inhalation, oral or intravenous rehydration, electrolyte correction, antipyretics, analgesics, antibiotics and antiemetic drugs \& the medication any patient is on due to any concomitant diseases.

Only Standard Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Male or female patients 18 -65 years old
• Respiratory samples tested positive for the novel coronavirus.
• Initial symptoms will within 7 days
• Nonpregnant women (confirmed by urine human chorionic gonadotropin (HCG) test prior to enrollment)

You may not qualify if:

• Severe clinical condition (meeting one of the following criteria: a resting respiratory rate greater than 30 per minute, oxygen saturation below 93%, oxygenation index (OI) \< 300 mmHg (1 mmHg = 133.3 Pa), respiratory failure, shock, and/or combined failure of other organs that required ICU monitoring and treatment).
• Chronic liver and kidney disease and reaching end stage. (Serum aspartate aminotransferase (AST) and Serum alanine aminotransferase (ALT) will be elevated over 5 times of normal upper range will excluded).
• (Normal upper limit of Serum AST = 40 units /L, ALT = 56 units /L)
• Serum uric acid \>7.0 mg/dL in Male and Serum uric acid \>6.0 mg/dL in Female will excluded
• ICU patient
• Previous history of allergic reactions to Favipiravir.
• Pregnant or lactating women
• Women of a childbearing age with a positive pregnancy test.
• Miscarriage, or within 2 weeks after delivery
• Hypertensive patients, who are taking Calcium Channel Blockers

Sponsors & Collaborators

• Bangladesh Medical Research Council (BMRC): lead

Study Sites (1)

Mahanagar General Hospital, Dhaka (Site-1), Mugda Medical College Hospital, Dhaka (Site-2), Kurmitola General Hospital, Dhaka (Site-3), Dhaka Medical College Hospital, Dhaka (Site-4)

Dhaka, Bangladesh

RECRUITING

Related Publications (9)

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

  PMID: 32031570 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Liu M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TTY, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29.

  PMID: 31995857 BACKGROUND

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-6736(20)30251-8. Epub 2020 Jan 30.

  PMID: 32007145 BACKGROUND

• Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. No abstract available.

  PMID: 32020029 BACKGROUND

• Oestereich L, Ludtke A, Wurr S, Rieger T, Munoz-Fontela C, Gunther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014 May;105:17-21. doi: 10.1016/j.antiviral.2014.02.014. Epub 2014 Feb 26.

  PMID: 24583123 BACKGROUND

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 BACKGROUND

• Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Gotte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem. 2020 Apr 10;295(15):4773-4779. doi: 10.1074/jbc.AC120.013056. Epub 2020 Feb 24.

  PMID: 32094225 BACKGROUND

Related Links

• Coronavirus disease 2019 (COVID-19) Situation Report
• Max Roser, Hannah Ritchie and Esteban Ortiz-Ospina
• Fujifilm commences Phase III trial of Avigan for Covid-19.
• Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase

MeSH Terms

Conditions

COVID-19

Interventions

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

Central Study Contacts

Ahmedul Kabir, MBBS, FCPS, FACP, FRCP

CONTACT

+88 01720910541; ahmedul_986@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled randomized control study. Randomization will be done by computerized randomization table Group A Patient (25) = Favipiravir + Standard Treatment Group B Patient (25) = Only Standard Treatment For better result sample size may be multiply on the basis of availability of COVID-19 patient in the study hospital.

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 26, 2020
• Study Start: May 1, 2020
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: May 26, 2020

Record last verified: 2020-05

Locations

BA (1)