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.
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.
Dietary Supplement: Antioxidation Therapy
Two proprietary formulations composed of reduced glutathione, N-acetylcysteine, superoxide dismutase, and bovine lactoferrin and immunoglobulins.
Other: Standard of Care
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
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
Abia State Isolation Centre, Amachara
Umuahia, Abia State, Nigeria
Benue State University Teaching Hospital
Makurdi, Benue State, Nigeria
Brigadier Abba Kyari Memorial Hospital
Borno, Borno State, Nigeria
University of Maiduguri Teaching Hospital
Maiduguri, Borno State, Nigeria
University of Calabar Teaching Hospital
Calabar, Cross River, Nigeria
Federal Medical Centre Idi-Aba
Abeokuta, Ogun State, Nigeria
Olabisi Onabanjo University Teaching Hospital
Sagamu, Ogun State, Nigeria
Infectious Disease Hospital
Amanawa, Sokoto State, Nigeria
Murtala Muhammad Speciaist Hospital
Sokoto, Sokoto State, Nigeria
Occupational Therapy Center
Sokoto, Sokoto State, Nigeria
Usmanu Danfodiyo University Teaching Hospital
Sokoto, Sokoto State, Nigeria
Adeniyi Olagunju, BPharm, MRes, PhD, Study Chair
Obafemi Awolowo University