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.
7,990 studies on the registry are indexed under COVID-19; 466 are open to participants now.
This study's enrollment of 150 is above the median of 102 across 4,364 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Royal College of Surgeons in Ireland - Medical University of Bahrain is the lead sponsor of 11 studies on the registry; 1 is open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Cardiac dysfunction that would preclude treatment with hydroxychloroquine:
Hepatic dysfunction defined as:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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, Statistical analysis plan, Clinical study report, Analytic code
Time frame: Dr Manaf will act as the data custodian and is responsible for the storage, handling and quality of the study data. Data will be collected in the case report form to allow for cross referencing to check validity. Study documents (paper and electronic) will be retained in a secure (kept locked when not in use) location during and after the trial has finished. All essential documents including source documents will be retained for a period of 5 years after study completion (last patient, last study point). A label stating the date after which the documents can be destroyed will be placed on the inside front cover of the case notes of trial participants.
Access criteria: Study documents (paper and electronic) will be retained in a secure (kept locked when not in use) location during and after the trial has finished.
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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Studies of the drugs tested here: Hydroxychloroquine · Favipiravir
Royal College of Surgeons in Ireland - Medical University of Bahrain