Antioxidant Therapy for COVID-19 Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Study to Evaluate Antioxidant Therapy for Moderate to Severe COVID-19 With or Without Comorbidities

Conditions
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Covid-19

Intervention / Treatment
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* Dietary Supplement: Antioxidation Therapy
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care (SOC)<br>Participants in this arm will receive SOC alone, which will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19 | Other: Standard of Care<br>* SOC will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19<br>|
| Experimental: SOC plus Intervention<br>Participants in this arm will receive SOC plus daily antioxidant supplement composed of two proprietary formulations that include reduced glutathione, N-acetylcysteine, superoxide dismutase, and bovine lactoferrin and immunoglobulins. | Dietary Supplement: Antioxidation Therapy<br>* Two proprietary formulations composed of reduced glutathione, N-acetylcysteine, superoxide dismutase, and bovine lactoferrin and immunoglobulins.<br>Other: Standard of Care<br>* SOC will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement | 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) | 28 days | 
| Time to SARS-CoV-2 negativity | Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at Day 14 | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status on day 14 | Clinical status as assessed with the seven-category ordinal scale on day 14 | 14 days | 
| Proportion of participants with SARS-CoV-2 PCR negative result at Day 7 |  | 7 days | 
| Proportion of participants with SARS-CoV-2 PCR negative result at Day 28 |  | 28 days | 
| 28 Day mortality |  | 28 days | 
| Duration of hospitalization in survivors |  | 28 days | 
| Time from treatment initiation to death |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV infection, COVID-19, coronavirus