A Study to Evaluate Antioxidant Therapy for Moderate to Severe COVID-19 With or Without Comorbidities
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 11
- 主要终点
- Time to clinical improvement
研究概览
简要总结
Finding effective strategies to treat or prevent the novel coronavirus disease that started in 2019 (COVID-19) is a global public health priority. Potential therapeutics and vaccines are now being investigated in over 1500 clinical trials. Clinical features of the disease include overproduction of reactive oxygen species which induces oxidative stress responses and contribute to acute lung injury. This presents a potential treatment strategy involving antioxidation therapy. In this pilot study, 90 COVID-19 patients aged 18-75 years will be recruited into two groups. The 45 patients in group 1 will receive the standard of care determined by their primary care providers while the 45 patients in group 2 will receive both the standard of care combined with daily antioxidant supplement for 14 days. All patients will be monitored for a total of 28 days with daily monitoring of symptoms and nasopharyngeal swab for SARS-CoV-2 test on days 3, 7, 14 and 28. The study will compare the following between the two groups: (1) the proportion of patients with clinical improvement (defined as live discharge from hospital, decrease of at least 2 points from baseline on a 7-point ordinal scale, or both), and (2) the proportion of patients with negative SARS-CoV-2 test by PCR on days 3, 7, and 14.
详细描述
Background: COVID-19 caused by SARS-CoV-2 is an unprecedented global public health challenge which as at 06 May 2020 has spread to over 210 with over 3.6 million cases including 250,000 deaths. More than 1500 clinical trials are currently ongoing in an unprecedented global search for potential therapeutics and vaccines. Certain clinical features of SARS-CoV-2 infection provide potential treatment strategies involving antioxidation therapy, including overproduction of reactive oxygen species which induces oxidative stress responses and contribute to acute lung injury.
Primary Outcome Measure: (1) the proportion of patients with clinical improvement (defined as live discharge from hospital, decrease of at least 2 points from baseline on a 7-point ordinal scale, or both), and (2) the proportion of patients with negative SARS-CoV-2 test by PCR on days 3, 7, and 14.
Study Design: Individuals within 18-75 years of age who receive a PCR positive test for COVID-19 and admitted at participating COVID-19 isolation and treatment centres will be invited to participate. Consenting individuals will be randomised 1:1 to receive either standard of care alone (control group) or standard of care plus daily antioxidant supplementation (intervention group). A total of 90 participants will be recruited in the Pilot Stage (n = 45 per arm). The Pivotal Stage will include 300 participants. Antioxidant therapy will be a formulation composed of reduced GSH, N-acetylcysteine, superoxide dismutase and bovine lactoferrin and immunoglobulin as in whey protein isolate. Clinical improvement will be evaluated daily using a 7-category ordinal scale. SARS-CoV-2 PCR test will be repeated on days 3, 7, 14 and 28.
Analysis: An interim analysis of data from the Pilot Stage will be conducted after the first 45 participants have completed days 1-14 of the study period. These data will provide valuable insights regarding possible revision of the design, conduct and analysis of the Pivotal Stage. Analysis of clinical improvement based on the 7-category ordinal scale will be performed using time-to-event data (patients will censored at 28-days of follow-up). Categorical variables will be analysed using the log-rank test and continuous variables will be assessed using a univariable Cox proportional hazard regression analysis. Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 3, 7, 14 and 28 will be compared between the intervention and control groups.
Ethics: This trial will be conducted in compliance with the protocol, the principles of ICH Guideline E6 for Good Clinical Practice, the Declaration of Helsinki, and all applicable regulatory requirements.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide informed consent prior to any study procedures
- •Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 2 days before randomization
- •Currently hospitalized and requiring medical care for COVID-19
- •Peripheral capillary oxygen saturation (SpO2) < 94% on room air at screening
- •Exclusion Criteria
- •Participation in any other clinical trial of an experimental treatment for COVID-19
- •Concurrent treatment with other agents outside the standard of care than 24 hours prior to study intervention dosing
- •Requiring mechanical ventilation at screening
- •Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN)
- •Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula
排除标准
- 未提供
结局指标
主要结局
Time to clinical improvement
时间窗: 28 days
Time to clinical improvement (defined as time from randomization to either an improvement of two points on a 7-category ordinal scale or discharge from the hospital, whichever came first, or both)
Time to SARS-CoV-2 negativity
时间窗: 14 days
Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at Day 14
次要结局
- Proportion of participants with SARS-CoV-2 PCR negative result at Day 7(7 days)
- Time from treatment initiation to death(28 days)
- Duration of hospitalization in survivors(28 days)
- Clinical status on day 14(14 days)
- Proportion of participants with SARS-CoV-2 PCR negative result at Day 28(28 days)
- 28 Day mortality(28 days)