A Phase 2 interventional study of Hydroxychloroquine and Favipiravir in SARS-CoV 2 and COVID-19, sponsored by Royal College of Surgeons in Ireland - Medical University of Bahrain. Completed at 1 site in Bahrain. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2021-10-26.
Sponsored by Royal College of Surgeons in Ireland - Medical University of Bahrain · Phase 2, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Cardiac dysfunction that would preclude treatment with hydroxychloroquine:
Hepatic dysfunction defined as:
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.
Drug: Hydroxychloroquine · Other: Routine care for COVID-19 patients
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).
Drug: Favipiravir · Other: Routine care for COVID-19 patients
Supportive care according to local guidelines
Other: Routine care for COVID-19 patients
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.
Also known as: Hydroxychloroquine sulfate, Plaquenil
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.
Also known as: Avigan, T-705, favipira, favilavir
Supportive care according to local guidelines
Also known as: Standard clinical care
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)
Time frame: Until discharge, death or for a maximum of 30 days or readmission
Requirement of Escalation of Respiratory Support
Implementation 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))
Monitor and document all adverse effects during therapy
Time frame: Until discharge,death or for a maximum of 14 days or readmission
Requirement of ICU Admission
Deterioration of clinical condition requiring ICU admission
Time frame: Until discharge, death or for a maximum of 14 days or readmission
Mortality rate
30 days Mortality rate due to COVID-19
Time frame: Mortality will be collected up to 30 days
Readmission rate
30 days readmission rate will be captured
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: until discharge, death or for a maximum of 30 days
Plan to share: 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.
Supporting information: Study protocol, Sap, Csr, Analytic code
This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.
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Royal College of Surgeons in Ireland - Medical University of Bahrain