Antioxidant Therapy for COVID-19 Study

NCT ID: NCT04466657

Last Updated: 2021-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-01

Study Completion Date

2021-04-30

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.

Conditions

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Covid-19

Keywords

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SARS-CoV infection COVID-19 coronavirus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Standard of Care (SOC)

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

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type OTHER

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

SOC plus Intervention

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.

Group Type EXPERIMENTAL

Antioxidation Therapy

Intervention Type DIETARY_SUPPLEMENT

Two proprietary formulations composed of reduced glutathione, N-acetylcysteine, superoxide dismutase, and bovine lactoferrin and immunoglobulins.

Standard of Care

Intervention Type OTHER

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

Interventions

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Antioxidation Therapy

Two proprietary formulations composed of reduced glutathione, N-acetylcysteine, superoxide dismutase, and bovine lactoferrin and immunoglobulins.

Intervention Type DIETARY_SUPPLEMENT

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

Intervention Type OTHER

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Borno State Ministry of Health

UNKNOWN

Sponsor Role collaborator

Ogun State Ministry of Health

UNKNOWN

Sponsor Role collaborator

Abia State Ministry of Health

UNKNOWN

Sponsor Role collaborator

Sokoto State Ministry of Health

UNKNOWN

Sponsor Role collaborator

Benue State Minsitry of Health

UNKNOWN

Sponsor Role collaborator

University of Calabar Teaching Hospital

UNKNOWN

Sponsor Role collaborator

Obafemi Awolowo University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adeniyi Olagunju, BPharm, MRes, PhD

Role: STUDY_CHAIR

Obafemi Awolowo University

Locations

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Abia State Isolation Centre, Amachara

Umuahia, Abia State, Nigeria

Site Status

Benue State University Teaching Hospital

Makurdi, Benue State, Nigeria

Site Status

Brigadier Abba Kyari Memorial Hospital

Borno, Borno State, Nigeria

Site Status

University of Maiduguri Teaching Hospital

Maiduguri, Borno State, Nigeria

Site Status

University of Calabar Teaching Hospital

Calabar, Cross River State, Nigeria

Site Status

Federal Medical Centre Idi-Aba

Abeokuta, Ogun State, Nigeria

Site Status

Olabisi Onabanjo University Teaching Hospital

Sagamu, Ogun State, Nigeria

Site Status

Infectious Disease Hospital

Ammanawa, Sokoto State, Nigeria

Site Status

Murtala Muhammad Speciaist Hospital

Sokoto, Sokoto State, Nigeria

Site Status

Occupational Therapy Center

Sokoto, Sokoto State, Nigeria

Site Status

Usmanu Danfodiyo University Teaching Hospital

Sokoto, Sokoto State, Nigeria

Site Status

Countries

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Nigeria

References

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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.

Reference Type BACKGROUND
PMID: 32325252 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18423196 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21471094 (View on PubMed)

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):13. doi: 10.3390/v8010013.

Reference Type BACKGROUND
PMID: 26761025 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32258207 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28853742 (View on PubMed)

Other Identifiers

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GSHSOD-COVID2020

Identifier Type: -

Identifier Source: org_study_id