SARS-CoV 2Phase 2NCT04387760
Favipiravir vs Hydroxychloroquine vs Control in COVID -19
A Phase 2 study testing Hydroxychloroquine, Favipiravir and Routine care for COVID-19 patients in people with SARS-CoV 2 and COVID-19, run by Royal College of Surgeons in Ireland - Medical University of Bahrain at 1 site in Bahrain.
Trial summary
Hydroxychloroquine is widely used to treat autoimmune diseases. Clinical investigation has found that a high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, therefore, hydroxychloroquine as anti-inflammatory agents may reduce this response in accord with… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- SARS-CoV 2, COVID-19
- What is being tested?
- Hydroxychloroquine, Favipiravir and Routine care for COVID-19 patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteBahrain
- Study dates
- 11 Aug 2020to 7 Apr 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted COVID-19 patients being treated as an in-patient at a hospital facility.
- 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.
Who cannot join
- Severe COVID-19 disease: defined as presence of SpO₂ less than 93% on room air or a PaO₂ to FiO₂ ratio of 300 or lower.
- Patients on ventilatory support.
- Cardiac dysfunction that would preclude treatment with hydroxychloroquine:
- Patients on medication known to prolong QT segment.
- Known history of LQT syndrome.
- Acquired QT prolongation at baseline >500ms.
Show all 25Show fewer
- AV block.
- Bundle Branch Block.
- Known history of Cardiomyopathy, Pulmonary Hypertension, or Sick Sinus Syndrome.
- History of ventricular tachyarrhythmia.
- Patients with implantable cardioverter-defibrillator (ICD).
- 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:
- Transaminitis more than three times the upper limit of normal or
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Covid-19 With Favipiravir Versus Hydroxychloroquine: a Randomized Comparator Trial
Hydroxychloroquine is widely used to treat autoimmune diseases. Clinical investigation has found that a high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, therefore, hydroxychloroquine as anti-inflammatory agents may reduce this response in accord with their use in autoimmune disease where the cytokine response can be reduced.
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.
Read the detailed description
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/2019-nCoV) and has developed into a pandemic with serious global public health and economic sequelae. As of June 30, 2020 over 10,000,000 cases have been confirmed worldwide leading to over 500,000 deaths (https://coronavirus.jhu.edu/map.html). Currently no vaccine exists, however chloroquine and hydroxychloroquine have been documented as potentially having antiviral properties with efficacy against COVID-19 disease. Chloroquine is used in the treatment of malaria and amebiasis and is still used in the prophylaxis of malaria. Hydroxychloroquine sulfate is a derivative of Chloroquine that has been demonstrated to be much less (~40%) toxic than Chloroquine in animals. 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. Clinical investigation has found that high concentrations of cytokines are detectable in the plasma of critically ill patients infected with SARS-CoV-2, suggesting that cytokine storm is associated with disease severity; therefore, Chloroquine/ hydroxychloroquine may reduce this response by acting as anti-inflammatory agents in accord with their use in autoimmune disease, where their reduction in cytokine response has been extensively researched and demonstrated.
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
- SARS-CoV 2, COVID-19
- Being tested
- Hydroxychloroquine, Favipiravir, Routine care for COVID-19 patients
- Keywords
- Favipiravir, hydroxychloroquine, COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Hydroxychloroquine sulfate, Plaquenil
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.
FavipiravirDrug
Also called Avigan, T-705, favipira, favilavir
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 patientsOther
Also called Standard clinical care
Supportive care according to local guidelines
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | 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. Receives: Drug: Hydroxychloroquine; Other: Routine care for COVID-19 patients |
| Favipiravir | Experimental | 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). Receives: Drug: Favipiravir; Other: Routine care for COVID-19 patients |
| Standard clinical care | Active comparator | Supportive care according to local guidelines Receives: Other: Routine care for COVID-19 patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome is the Medial clinical scale at end of study follow up
Median clinical scale at end of study follow up (day 14 or on discharge/death, whichever is earlier)
Measured: Until discharge, death or for a maximum of 30 days or readmission
Secondary outcomes (12)
Requirement of Escalation of Respiratory Support
Implementation of escalation of Respiratory Support
Measured: Until discharge, death or for a maximum of 14 days or readmission
Adverse effects(cardiac, renal, hepatic, hypoglycaemia (defined as RBS <3.9 mmol/L))
Monitor and document all adverse effects during therapy
Measured: Until discharge,death or for a maximum of 14 days or readmission
Requirement of ICU Admission
Deterioration of clinical condition requiring ICU admission
Measured: Until discharge, death or for a maximum of 14 days or readmission
Mortality rate
30 days Mortality rate due to COVID-19
Measured: Mortality will be collected up to 30 days
Readmission rate
30 days readmission rate will be captured
Measured: Readmission will be collected up to 30 days from start of the study
Daily National Early Warning (NEWS) 2 Score
Daily NEWS 2 will be calculated which is a tool that improves the detection and response to clinical deterioration in adult patients and is a key element of patient safety and improving patient outcomes
Measured: Until discharge, death or for a maximum of 14 days
Daily Sequential Organ Failure Assessment (SOFA) score
Daily SOFA score will be calculated which can identify the critical point at which patients exhibit the highest degree of organ dysfunction
Measured: Until discharge, death or for a maximum of 14 days
Change in Laboratory indices
Determination of the change in D-dimer, ratio of Lymphocyte to Neutrophil, lactate before and after treatments as a measure of disease activity
Measured: Until discharge, death or for a maximum of 14 days
Discharge and Length of Hospital Stay
Patients will be followed during their hospital stay until discharge
Measured: Until discharge, death or for a maximum of 14 days
QT prolongation
Determination of the change in QT prolongation, before and after treatments as a measure of disease activity
Measured: Until discharge, death or for a maximum of 14 days or readmission
Cardiac arrythmia (fatal and non fatal)
Detection of Cardiac arrythmia (fatal and non fatal), before and after treatments as a measure of disease activity
Measured: Until discharge, death or for a maximum of 14 days or readmission
Viral clearance
Viral clearance defined as a single negative SARS-CoV2 PCR nasopharyngeal swab
Measured: until discharge, death or for a maximum of 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start11 Aug 2020
- Primary completion6 Mar 2021
- Study completion7 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a parallel, prospective, interventional and randomized open label pilot trial involving 150 patients with COVID-19 disease. On confirmation of SARS-CoV-2 infection subjects will be randomised to hydroxychloroquine or favipiravir or standard clinical care.
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons in Ireland - Medical University of Bahrain
- Sponsor type
- University, hospital or other
- Collaborators
- Ebrahim Khalil Kanoo Community Medical Center, Hereditary blood Disorder Centre - Salmaniya Medical Complex, Mohammed Bin Khalifa Bin Sulman Al Khalifa Cardiac Centre, Awali, Jidhafs COVID-19 Centre, Sitra FICU, Salmaniya Medical Complex- 6th Floor, Salmaniya Medical Complex- Helipad
- Responsible party
- Sponsor
- Investigators
- Manaf Al Qahtani, Dr., Principal investigator, Royal College of Surgeons in Ireland - Bahrain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04387760
- Sponsor's protocol ID
- 40 / 07-May-2020
- Status last verified
- Aug 2021
- First submitted
- 9 May 2020
- Last updated
- 26 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Monitoring, audits, and REC review will be permitted and provide direct access to source data and documents. The Lead PI and the researchers assigned by him will have access to the stored data/specimens. Only the Lead PI and the researchers assigned working on this study will be eligible to obtain the data/specimens from the participants during data collection.
Publications
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.
PubMed 6408923Liu 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.
PubMed 32194981Huang 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.
PubMed 31986264Delang 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.
PubMed 29524445Dong 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.
PubMed 32147628Cai 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.
PubMed 32346491Gautret 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.
PubMed 32205204Birkett 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.
PubMed 7701146Senn SJ. Covariate imbalance and random allocation in clinical trials. Stat Med. 1989 Apr;8(4):467-75. doi: 10.1002/sim.4780080410.
PubMed 2727470Senn S. Testing for baseline balance in clinical trials. Stat Med. 1994 Sep 15;13(17):1715-26. doi: 10.1002/sim.4780131703.
PubMed 7997705Knol 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.
PubMed 22512015AlQahtani 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.
PubMed 35322077
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Covid-19 With Favipiravir Versus Hydroxychloroquine: a Randomized Comparator Trial
- ClinicalTrials.gov ID
- NCT04387760
- Acronym / sponsor ID
- 40 / 07-May-2020
- Conditions
- SARS-CoV 2, COVID-19
- Keywords
- Favipiravir, hydroxychloroquine, COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Royal College of Surgeons in Ireland - Medical University of BahrainUniversity, hospital or other
- Collaborators
- Ebrahim Khalil Kanoo Community Medical Center, Hereditary blood Disorder Centre - Salmaniya Medical Complex, Mohammed Bin Khalifa Bin Sulman Al Khalifa Cardiac Centre, Awali, Jidhafs COVID-19 Centre, Sitra FICU, Salmaniya Medical Complex- 6th Floor, Salmaniya Medical Complex- Helipad
- Study start
- 11 Aug 2020 (actual)
- Primary completion
- 6 Mar 2021 (actual)
- Study completion
- 7 Apr 2021 (actual)
- First posted
- 14 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hydroxychloroquine is widely used to treat autoimmune diseases. Clinical investigation has found that a high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, therefore, hydroxychloroquine as anti-inflammatory agents may reduce this response in accord with their use in autoimmune disease where the cytokine response can be reduced.
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
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/2019-nCoV) and has developed into a pandemic with serious global public health and economic sequelae. As of June 30, 2020 over 10,000,000 cases have been confirmed worldwide leading to over 500,000 deaths (https://coronavirus.jhu.edu/map.html). Currently no vaccine exists, however chloroquine and hydroxychloroquine have been documented as potentially having antiviral properties with efficacy against COVID-19 disease. Chloroquine is used in the treatment of malaria and amebiasis and is still used in the prophylaxis of malaria. Hydroxychloroquine sulfate is a derivative of Chloroquine that has been demonstrated to be much less (~40%) toxic than Chloroquine in animals. 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. Clinical investigation has found that high concentrations of cytokines are detectable in the plasma of critically ill patients infected with SARS-CoV-2, suggesting that cytokine storm is associated with disease severity; therefore, Chloroquine/ hydroxychloroquine may reduce this response by acting as anti-inflammatory agents in accord with their use in autoimmune disease, where their reduction in cytokine response has been extensively researched and demonstrated.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a parallel, prospective, interventional and randomized open label pilot trial involving 150 patients with COVID-19 disease. On confirmation of SARS-CoV-2 infection subjects will be randomised to hydroxychloroquine or favipiravir or standard clinical care.
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Experimental | Drug: Hydroxychloroquine, Other: Routine care for COVID-19 patientsHydroxychloroquine 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. |
| Favipiravir | Experimental | Drug: Favipiravir, Other: Routine care for COVID-19 patientsFavipiravir 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). |
| Standard clinical care | Active comparator | Other: Routine care for COVID-19 patientsSupportive care according to local guidelines |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Admitted COVID-19 patients being treated as an in-patient at a hospital facility.
- 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.
Key exclusion criteria (25 listed)
- Severe COVID-19 disease: defined as presence of SpO₂ less than 93% on room air or a PaO₂ to FiO₂ ratio of 300 or lower.
- Patients on ventilatory support.
- Cardiac dysfunction that would preclude treatment with hydroxychloroquine:
- Renal dysfunction (estimated glomerular filtration rate less than 30ml/min).
- Hepatic dysfunction defined as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineAlso: Hydroxychloroquine sulfate, Plaquenil400mg 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. | Drug | Hydroxychloroquine |
| FavipiravirAlso: Avigan, T-705, favipira, favilavir1600mg 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. | Drug | Favipiravir |
| Routine care for COVID-19 patientsAlso: Standard clinical careSupportive care according to local guidelines | Other | Favipiravir, Hydroxychloroquine, Standard clinical care |
Primary outcome
Primary outcome is the Medial clinical scale at end of study follow up
Time frame: Until discharge, death or for a maximum of 30 days or readmission
Median clinical scale at end of study follow up (day 14 or on discharge/death, whichever is earlier)
12 secondary outcomes
Requirement of Escalation of Respiratory Support
Time frame: Until discharge, death or for a maximum of 14 days or readmission
Adverse effects(cardiac, renal, hepatic, hypoglycaemia (defined as RBS <3.9 mmol/L))
Time frame: Until discharge,death or for a maximum of 14 days or readmission
Requirement of ICU Admission
Time frame: Until discharge, death or for a maximum of 14 days or readmission
Mortality rate
Time frame: Mortality will be collected up to 30 days
Readmission rate
Time frame: Readmission will be collected up to 30 days from start of the study
Daily National Early Warning (NEWS) 2 Score
Time frame: Until discharge, death or for a maximum of 14 days
Daily Sequential Organ Failure Assessment (SOFA) score
Time frame: Until discharge, death or for a maximum of 14 days
Change in Laboratory indices
Time frame: Until discharge, death or for a maximum of 14 days
Discharge and Length of Hospital Stay
Time frame: Until discharge, death or for a maximum of 14 days
QT prolongation
Time frame: Until discharge, death or for a maximum of 14 days or readmission
Cardiac arrythmia (fatal and non fatal)
Time frame: Until discharge, death or for a maximum of 14 days or readmission
Viral clearance
Time frame: until discharge, death or for a maximum of 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2021.
- Background: PubMed 6408923McChesney 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.
- Background: PubMed 32194981Liu 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.
- Background: PubMed 31986264Huang 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.
- Background: PubMed 29524445Delang 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.
- Background: PubMed 32147628Dong 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.
- Background: PubMed 32346491Cai 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.
- Background: PubMed 32205204Gautret 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.
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- Derived from this study: PubMed 35322077AlQahtani 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.
- Individual participant dataSharing planned: Yes. Monitoring, audits, and REC review will be permitted and provide direct access to source data and documents. The Lead PI and the researchers assigned by him will have access to the stored data/specimens. Only the Lead PI and the researchers assigned working on this study will be eligible to obtain the data/specimens from the participants during data collection.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manaf Al Qahtani, Dr. principal investigator
Royal College of Surgeons in Ireland - Bahrain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine, Favipiravir and Routine care for COVID-19 patients in people with SARS-CoV 2 and COVID-19, run by Royal College of Surgeons in Ireland - Medical University of Bahrain at 1 site in Bahrain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bahrain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary outcome is the Medial clinical scale at end of study follow up (time frame: Until discharge, death or for a maximum of 30 days or readmission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04387760, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2021.