Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoC-2 Virus Infection (COVID-19). A Pilot, Randomized, Simple Blind, Placebo-controlled, Parallel-group Study
试验速览
- 阶段
- 2 期
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th.
研究概览
简要总结
Evaluation of the efficacy and safety of NTX in adult patients (≥18 years and <60 years), with SARS-CoV-2 infection with mild symptoms of COVID-19, compared to a placebo control arm. 135 patients will be randomized to either Nitazoxanide (n=90) or placebo (n=45) (2:1). Simple blind design. Primary endpoint: eradication of virus from patients' respiratory tract secretions by the 7th day of treatment.
详细描述
The rapid spread of COVID-19 has overwhelmed the capabilities of the Public Health System in major nations due to the large number of critically ill patients and patients seriously affected requiring intensive care.
Reducing the viral load, along with other epidemiological measures, including social isolation and quarantine, may in the long run significantly reduce the R0 (Basic Reproductive Rhythm) of infection.
To date, in our country there are no specific antiviral treatments approved by the regulatory authorities for COVID-19, and no vaccines so far exist. Symptomatic and supportive treatment has been the main intervention for patients with moderate to severe infection.
The lack of a drug with a demonstrated solid antiviral efficacy warrants the need to explore new therapeutic options against SARS-CoV-2 / COVID-19.
Nitazoxanide is a widely used thiazolide, approved by the FDA and ANMAT (Argentine drug regulatory authority) as an antiprotozoal, with a very good safety record for a variety of indications. NTX was shown to have extensive antiviral activity against, inter alia, animal and human coronaviruses. Indeed, it exhibits in vitro activity against MERS-CoV and other coronaviruses, including SARS-CoV-2, where it inhibits the expression of viral protein N. Another proposed antiviral mechanism for Nitazoxanide involves PKR and eIF2α phosphorylation and the depletion of ATP-sensitive intracellular calcium deposits in infected cells, thereby inducing chronic sub-lethal stress of the endoplasmic reticulum and impairing the glycosylation of the structural protein.
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
- Single (Participant)
盲法说明
Simple blind design
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male and female patients (≥ 18 years and <60 years).
- •Signature of informed consent.
- •Patients with a positive test for SARS-CoV-2 and mild symptoms of COVID-19 (without severity criteria as detailed by the Ministry of Health of Argentina - MSN)
排除标准
- •Patients under 18 years of age and over 60 years of age.
- •Breastfeeding or pregnant women (with positive pregnancy blood test in women of childbearing age).
- •Patients with mild pneumonia in the presence of risk factors or moderate or severe pneumonia (based on the severity criteria set by the Ministry of Health of Argentina), or patients who require mechanical ventilation at screening.
- •Patients in whom NTX and/or lactose is contraindicated.
- •Any other contraindication based on the judgment of the treating physician.
研究组 & 干预措施
NTX active treatment
Intervention: NTX (500 mg every 6 hours for 14 days) orally with food (P.O.).
干预措施: Nitazoxanide (Drug)
Intervention: placebo
Placebo (1 tablet every 6 hours for 14 days) orally with food (P.O.).
干预措施: Placebo (Drug)
结局指标
主要结局
Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th.
时间窗: 7 day
Erradication will be considered a reduction of the viral load on day 7 greater than 35% with respect to placebo. Extraction of genomic material will be performed using a QIAgen mini kit (QIAmp viral RNA) validated by the CDC (United States Center for Disease Control and Prevention (https://www.fda.gov/media/134922/download) (CDC-006-00019) Viral load will be quantified with the following detection kits: Commercial Kit: PCR-EUA-CDC-nCoV-IFU. Commercial KIT SENTINEL - STAT-NAT Covid 19B (Berlín). Rational: In mild cases of COVID-19, 50% of the patients eradicated the virus within a period of 3 weeks, 25% eradicated the virus before the 13th day, 75% during the first month and the rest were " late eradicators." This latter subgroup of patients has been associated with severe cases of COVID-19 disease.
次要结局
- Clinical improvement(1 - 35 days)
- Pneumonia patients meeting severity criteria.(1 - 35 days)
- Number of days with fever(1 - 35 days)
- Comparative decrease of the viral load(3 - 35 days)