Favipiravir vs Hydroxychloroquine vs Control in COVID -19
NCT ID: NCT04387760
Last Updated: 2021-10-26
Study Results
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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COMPLETED
PHASE2
150 participants
INTERVENTIONAL
2020-08-11
2021-04-07
Brief Summary
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Favipiravir is an antiviral drug developed in Japan that the data sheet notes that it is a pyrazinecarboxamide derivative with activity against influenza viruses, west nile virus, yellow fever virus, foot and mouth disease virus as well as against flaviviruses, arenaviruses, bunyaviruses and alphaviruses. In February the drug was used for COVID-19 disease in China and was declared effective in treatment, and a report published (in press) comparing Favipiravir with Lopinavir /ritonavir suggested that Favipiravir was superior for prevention of disease progression and viral clearance.
The objective of this pilot study is to compare three arms: hydroxychloroquine; favipiravir; standard care (no specific SARS-CoV-2 treatment) only, in symptomatic patients infected by SARS-CoV-2 in an open label randomized clinical trial. The difference between groups will allow an effect size to be determined for a definitive clinical trial.
Detailed Description
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Favipiravir is an antiviral drug developed in Japan (as noted in the data sheets) that it is a pyrazinecarboxamide derivative with activity against influenza viruses, west nile virus, yellow fever virus, foot and mouth disease virus as well as against flaviviruses (i.e. arenaviruses, bunyaviruses and alphaviruses). Its mode of action is through inhibition of viral RNA-dependent RNA polymerase. In February the drug was used for COVID-19 disease in China and was declared effective in treatment, and a report published (in press) comparing Favipiravir with Lopinavir /ritonavir suggested that Favipiravir was superior for prevention of disease progression and viral clearance.
"The Solidarity Trial" is a global pragmatic clinical trial being undertaken by WHO that aims to explore the efficacy of different treatment modalities for SARS-CoV-2. An application for Bahrain to join the study for collaboration has been made. In "The Solidarity Study" there will be four treatment modalities investigated, including chloroquine phosphate alone, remdesivir, lopinarvir with ritonavir or lopinarvir with ritonavir plus interferon. Favipiravir is not included, and therefore this study will not be replicating features of "The Solidarity Trial" but instead will provide additional and novel findings on favipiravir efficacy.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Hydroxychloroquine
Hydroxychloroquine is widely used to treat autoimmune diseases, due to its immunomodulatory properties, such as systemic lupus erythematosus and rheumatoid arthritis, with an excellent safety profile. In vitro studies have suggested that their mode of action in COVID-19 disease is blockade of SARS-CoV-2 transport from endosomes to endolysosomes, which appears to be a requirement to release the viral genome.
Hydroxychloroquine
400mg BID PO day 1 then 200mg BID PO from day 2 to day 10.
In addition to Hydroxychloroquine all patients will receive the standard care (according to local Bahrain COVID19 guidelines). Any patient who is fit for discharge, can be discharged and medications will be stopped on discharge.
Routine care for COVID-19 patients
Supportive care according to local guidelines
Favipiravir
Favipiravir is an antiviral drug that it is a pyrazinecarboxamide derivative with activity against influenza viruses, west nile virus, yellow fever virus, foot and mouth disease virus as well as against flaviviruses (i.e. arenaviruses, bunyaviruses and alphaviruses).
Favipiravir
1600mg BID PO day 1600mg BID PO day 2 to day 10.
In addition to Favipiravir all patients will receive the standard care (according to local Bahrain COVID19 guidelines). Any patient who is fit for discharge, can be discharged and medications will be stopped on discharge.
Routine care for COVID-19 patients
Supportive care according to local guidelines
Standard clinical care
Supportive care according to local guidelines
Routine care for COVID-19 patients
Supportive care according to local guidelines
Interventions
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Hydroxychloroquine
400mg BID PO day 1 then 200mg BID PO from day 2 to day 10.
In addition to Hydroxychloroquine all patients will receive the standard care (according to local Bahrain COVID19 guidelines). Any patient who is fit for discharge, can be discharged and medications will be stopped on discharge.
Favipiravir
1600mg BID PO day 1600mg BID PO day 2 to day 10.
In addition to Favipiravir all patients will receive the standard care (according to local Bahrain COVID19 guidelines). Any patient who is fit for discharge, can be discharged and medications will be stopped on discharge.
Routine care for COVID-19 patients
Supportive care according to local guidelines
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* COVID-19 diagnosis confirmed by PCR nasopharyngeal swab.
* Study participants must be symptomatic with any COVID-19 symptoms defined by the Bahrain National Protocol
* Onset of symptoms must be within 10 days prior to enrolment.
* Study participants must have the ability to give informed consent.
* Participants must be at minimum 21 years of age.
* Mild to Moderate COVID-19 disease defined as saturation equals to or more than 93% on room air or PaO2:FiO2 ratio more than 300 on enrolment.
Exclusion Criteria
* Patients on ventilatory support.
* Cardiac dysfunction that would preclude treatment with hydroxychloroquine:
1. Patients on medication known to prolong QT segment.
2. Known history of LQT syndrome.
3. Acquired QT prolongation at baseline \>500ms.
4. AV block.
5. Bundle Branch Block.
6. Known history of Cardiomyopathy, Pulmonary Hypertension, or Sick Sinus Syndrome.
7. History of ventricular tachyarrhythmia.
8. Patients with implantable cardioverter-defibrillator (ICD).
9. Patients with a baseline bradycardia of less than 50 beats per minute.
* Renal dysfunction (estimated glomerular filtration rate less than 30ml/min).
* Hepatic dysfunction defined as:
1. Transaminitis more than three times the upper limit of normal or
2. Chronic liver disease of Child Pugh Class B or higher.
* Gout or a history of gout
* Patients that are pregnant or breastfeeding.
* Patients with a known allergy to an intervention medication.
* Patients who receive any of the study medications prior to randomization
* Patient with G6PD
* Readmission due to COVID19 disease.
* Participants in any other COVID-19 disease trial.
* Patients on immunosuppressants, HIV patients, cancer patients who received chemotherapy within the past 6 months, or who are on chronic oral steroids.
* Patients unable to give informed consent.
21 Years
ALL
No
Sponsors
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Ebrahim Khalil Kanoo Community Medical Center
UNKNOWN
Hereditary blood Disorder Centre - Salmaniya Medical Complex
UNKNOWN
Mohammed Bin Khalifa Bin Sulman Al Khalifa Cardiac Centre, Awali
UNKNOWN
Jidhafs COVID-19 Centre
UNKNOWN
Sitra FICU
UNKNOWN
Salmaniya Medical Complex- 6th Floor
UNKNOWN
Salmaniya Medical Complex- Helipad
UNKNOWN
Royal College of Surgeons in Ireland - Medical University of Bahrain
OTHER
Responsible Party
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Principal Investigators
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Manaf Al Qahtani, Dr.
Role: PRINCIPAL_INVESTIGATOR
Royal College of Surgeons in Ireland - Bahrain
Locations
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Royal College of Surgeons in Ireland - Bahrain
Manama, , Bahrain
Countries
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References
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McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983 Jul 18;75(1A):11-8. doi: 10.1016/0002-9343(83)91265-2.
Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020. No abstract available.
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.
Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018 May;153:85-94. doi: 10.1016/j.antiviral.2018.03.003. Epub 2018 Mar 7.
Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. doi: 10.5582/ddt.2020.01012.
Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, Liao X, Gu Y, Cai Q, Yang Y, Shen C, Li X, Peng L, Huang D, Zhang J, Zhang S, Wang F, Liu J, Chen L, Chen S, Wang Z, Zhang Z, Cao R, Zhong W, Liu Y, Liu L. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing). 2020 Oct;6(10):1192-1198. doi: 10.1016/j.eng.2020.03.007. Epub 2020 Mar 18.
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.
Birkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. 1994 Dec 15-30;13(23-24):2455-63. doi: 10.1002/sim.4780132309.
Senn SJ. Covariate imbalance and random allocation in clinical trials. Stat Med. 1989 Apr;8(4):467-75. doi: 10.1002/sim.4780080410.
Senn S. Testing for baseline balance in clinical trials. Stat Med. 1994 Sep 15;13(17):1715-26. doi: 10.1002/sim.4780131703.
Knol MJ, Groenwold RH, Grobbee DE. P-values in baseline tables of randomised controlled trials are inappropriate but still common in high impact journals. Eur J Prev Cardiol. 2012 Apr;19(2):231-2. doi: 10.1177/1741826711421688. No abstract available.
AlQahtani M, Kumar N, Aljawder D, Abdulrahman A, Mohamed MW, Alnashaba F, Fayyad MA, Alshaikh F, Alsahaf F, Saeed S, Almahroos A, Abdulrahim Z, Otoom S, Atkin SL. Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease. Sci Rep. 2022 Mar 23;12(1):4925. doi: 10.1038/s41598-022-08794-w.
Other Identifiers
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40 / 07-May-2020
Identifier Type: -
Identifier Source: org_study_id