Study on Safety and Efficacy of Favipiravir (Favipira) for COVID-19 Patient in Selected Hospitals of Bangladesh
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of participants negative by RT-PCR for the virus at 4-10 days after initiation of therapy.
研究概览
简要总结
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).
详细描述
•Rationale: Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China. It was initially reported to the World Health Organization (WHO) on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency. On March 11, 2020, the WHO declared COVID-19 a global pandemic, its first such designation since declaring influenza A virus subtype (H1N1) influenza a pandemic in 2009. No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies Fujifilm Toyama Chemical has started a Phase III clinical trial of its antiviral influenza drug Avigan (favipiravir) for the treatment of Covid-19 patients in Japan. Avigan specifically blocks RNA polymerase associated with influenza viral replication. The mechanism is expected to have an antiviral effect on SARS-CoV-2, the novel coronavirus that causes Covid-19. In Japan, the new Phase III trial will assess Avigan's safety and efficacy as a potential Covid-19 treatment. Last month, China's Science and Technology Ministry official Zhang Xinmin said that favipiravir helped patients recover in an 80-day participant trial conducted in Shenzhen city.
According to the study data, the drug was able to shorten the recovery time from 11 days to four days for mild and moderate cases. Favipiravir secured Chinese approval for manufacturing by Zhejiang Hisun Pharmaceutical to treat adults with new or recurring influenza. It also holds approval in China as an investigational treatment for Covid-19. A drug developed by Fujifilm Toyama Chemical in Japan is showing promising outcomes in treating at least mild to moderate cases of COVID-19, Live Science previously reported. The antiviral drug, called Favipiravir or Avigan, has been used in Japan to treat influenza, and last month, the drug was approved as an experimental treatment for COVID-19 infection. The drug, which works by preventing certain viruses from replicating, seemed to shorten the duration of the virus as well as improve lung conditions (as seen in X-rays) in tested patients.
A few studies have been published in international journals regarding the efficacy and safety of Favipiravir. However, this type of study on Favipiravir (Favipira) has not yet been done in our country. This is the rationale why we have designed this clinical trial in Bangladesh to fight against COVID-19 a global pandemic.
Objectives:
•General Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Favipiravir + Standard Treatment
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.
干预措施: Favipiravir (Drug)
Only Standard Treatment
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.
干预措施: Only Standard Treatment (Drug)
结局指标
主要结局
Number of participants negative by RT-PCR for the virus at 4-10 days after initiation of therapy.
时间窗: at 4 to 10 days 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.
Number of participants with lung condition change assessed with X-ray.
时间窗: at Day-4, Day-7 and Day-10 of therapy
X-ray findings of lung condition improvement at Day-4, Day-7 and Day-10 of therapy
次要结局
- 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 participants with clinical recovery(at Day-4, Day-7 and Day-10 of therapy)
- Number of death(at Day-4, Day-7 and Day-10 of therapy)