Antioxidant Therapy for COVID-19 Study

Covid-19 Clinical Trial

— GSHSOD-COVID  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04466657
• Other study ID #: GSHSOD-COVID2020
• Status: Withdrawn
• Phase: N/A
• Start date: November 1, 2020
• Est. completion date: April 30, 2021

Study information

• Verified date: October 2021
• Source: Obafemi Awolowo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 30, 2021
• Est. primary completion date: February 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Covid-19

Intervention

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

Locations

Country	Name	City	State
Nigeria	Federal Medical Centre Idi-Aba	Abeokuta	Ogun State
Nigeria	Infectious Disease Hospital	Amanawa	Sokoto State
Nigeria	Brigadier Abba Kyari Memorial Hospital	Borno	Borno State
Nigeria	University of Calabar Teaching Hospital	Calabar	Cross River
Nigeria	University of Maiduguri Teaching Hospital	Maiduguri	Borno State
Nigeria	Benue State University Teaching Hospital	Makurdi	Benue State
Nigeria	Olabisi Onabanjo University Teaching Hospital	Sagamu	Ogun 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	Abia State Isolation Centre, Amachara	Umuahia	Abia State

Sponsors (7)

Lead Sponsor	Collaborator
Obafemi Awolowo University	Abia State Ministry of Health, Benue State Minsitry of Health, Borno State Ministry of Health, Ogun State Ministry of Health, Sokoto State Ministry of Health, University of Calabar Teaching Hospital

Country where clinical trial is conducted

Nigeria, 

References & Publications (6)

Cao W, Liu X, Bai T, Fan H, Hong K, Song H, Han Y, Lin L, Ruan L, Li T. High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019. Open Forum Infect Dis. 2020 Mar 21;7(3):ofaa102. doi: 10.1093/ofid/ofaa102. eCollection 2020 Mar. — View Citation

Hosakote YM, Jantzi PD, Esham DL, Spratt H, Kurosky A, Casola A, Garofalo RP. Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med. 2011 Jun 1;183(11):1550-60. doi: 10.1164/rccm.201010-1755OC. Epub 2011 Mar 4. — View Citation

Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung YH, Wang H, Liu H, Sun Y, Pasparakis M, Kopf M, Mech C, Bavari S, Peiris JS, Slutsky AS, Akira S, Hultqvist M, Holmdahl R, Nicholls J, Jiang C, Binder CJ, Penninger JM. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008 Apr 18;133(2):235-49. doi: 10.1016/j.cell.2008.02.043. — View Citation

Lin X, Wang R, Zou W, Sun X, Liu X, Zhao L, Wang S, Jin M. The Influenza Virus H5N1 Infection Can Induce ROS Production for Viral Replication and Host Cell Death in A549 Cells Modulated by Human Cu/Zn Superoxide Dismutase (SOD1) Overexpression. Viruses. 2016 Jan 8;8(1). pii: E13. doi: 10.3390/v8010013. — View Citation

Sinha R, Sinha I, Calcagnotto A, Trushin N, Haley JS, Schell TD, Richie JP Jr. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018 Jan;72(1):105-111. doi: 10.1038/ejcn.2017.132. Epub 2017 Aug 30. — View Citation

Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020 Jun;215:108427. doi: 10.1016/j.clim.2020.108427. Epub 2020 Apr 20. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events during treatment		28 days
Other	Serious adverse events	Respiratory failure or Acute Respiratory Distress Syndrome, Acute Kidney Injury, secondary infection, shock, severe anemia, acute gastritis, unconsciousness, acute heart failure	28 days
Other	Gastrointesntinal adverse events	Nausea, vomiting, and diarrhea	28 days
Other	Discontinuation of trial intervention before the end of protocol specified 14 days		14 days
Primary	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
Primary	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	Clinical status on day 14	Clinical status as assessed with the seven-category ordinal scale on day 14	14 days
Secondary	Proportion of participants with SARS-CoV-2 PCR negative result at Day 7		7 days
Secondary	Proportion of participants with SARS-CoV-2 PCR negative result at Day 28		28 days
Secondary	28 Day mortality		28 days
Secondary	Duration of hospitalization in survivors		28 days
Secondary	Time from treatment initiation to death		28 days

External Links

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