Safety and Efficacy of COVIDEX™ Therapy in Management of Adult COVID-19 Patients in Uganda. (COT)

Safety and Efficacy of COVIDEX™ Therapy in Management of Adult Covid-19 Patients in Uganda: A Randomized Double-blind Placebo Controlled Adaptive Phase 2 B Clinical Trial.

The SARS-CoV-2 pandemic continues to grow, with over 350,000 new infections and over 7,000 daily global deaths in May 2021 (WHO, 2021a). The current supplies of protective vaccines are too low to cover the worldwide demand hence researchers worldwide are urgently looking for interventions to prevent new infections, prevent disease progression, and lessen disease severity for those already infected.

While a number of claims on efficacy of herbal remedies on COVID-19 have been made, to our knowledge none of such claims have gained on scientific basis for continued use or further research and development of the constituents into investigational products.

In Uganda, one of such herbal remedies is COVIDEX, this study therefore seeks to investigate the safety and efficacy of COVIDEX in the management of COVID-19.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: COVIDEX

Detailed Description

The SARS-CoV-2 pandemic continues to grow, with over 350,000 new infections and over 7,000 daily global deaths in May 2021 (WHO, 2021a). The current supplies of protective vaccines are too low to cover the worldwide demand hence researchers globally are urgently looking for interventions to prevent new infections, prevent disease progression, and lessen disease severity for those already infected. According to data released by the ministry of health, Uganda had 94,904 confirmed cases with 2752 deaths at the end of July 2021 (MoH, 2021). Fortunately, most of the cases confirmed had a mild illness for whom home-based symptomatic management with monitoring of clinical deterioration as per World Health Organization recommendations is sufficing (WHO, 2021b). However, despite providing symptomatic management, a therapeutic drug that would limit infection is greatly needed to stop COVID-19 disease progression. While a number of claims on efficacy of herbal remedies on COVID-19 have been made, to our knowledge none of such claims have gained on scientific basis for continued use or further research and development of the constituents into investigational products.

COVIDEX is a herbal formulation containing berberine as a primary anti-SARSCOV-2 compound notified by the Uganda National Drug Authority for supportive treatment in managing viral infections. Notably, this notification was done with a call for clinical trials to validate the claims of its anti-SARS COV-2 activity. This study therefore proposes to investigate the safety and efficacy of COVIDEXTm therapy in managing COVID-19 disease.

• Study Type: Interventional
• Enrollment (Anticipated): 584
• Phase: Phase 2

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda, 7072
    • Makerere University Department of Pharmacology and Therapeutics
    • Contact: Jackson Mukonzo, PhD; Phone Number: +256758113468; Email: mukojack@yahoo.co.uk
    • Contact: SANDRA NALUYIMA, Msc; Phone Number: +256702954895; Email: sannaluyima@yahoo.com
    • Principal Investigator: Joseph Ngozi, MMED
    • Sub-Investigator: Lydia Bunalema, PhD
    • Sub-Investigator: Milton Mutto, PhD
    • Sub-Investigator: Fred Kyeyune, PhD
    • Sub-Investigator: Hellen Aanyu, MMED
    • Sub-Investigator: Rose Muhindo, MMED
    • Sub-Investigator: John Ssenkusu, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed/thumb printed and dated informed consent form
2. Willingness to comply with all study procedures and availability over the study duration
3. Patients aged 18years and above
4. Positive SARS-CoV-2 antigen rapid test and/or PCR positive for SARS-Cov-2 (COVID-19)
5. Symptomatic patients in the following categories; mild, moderate and severe: mild score 2 (limitation of activities), Moderately ill COVID-19 patients WHO score 3(Hospitalized with no oxygen therapy), which translates to moderately ill patients according to MOH Uganda, WHO Score 4 (Hospitalized with oxygen by mask or nasal prongs) and WHO score 5 (Non-invasive ventilation or high flow oxygen) which translates to severe COVID-19 disease on high flow oxygen patients according to the MOH Uganda COVID-19 disease category.

Exclusion Criteria:

1. Patients who report use of COVIDEX with-in three days prior to presentation to the hospital.
2. Clinical diagnosis of severe renal (defined by GFR ≤ 29 mL/min/1.73 m2) and hepatic impairment (defined by >2.5 times the upper normal value of ALT and AST).
3. Pregnancy or breast feeding.
4. Current use of remdesivir and molnupiravir therapy.
5. Active participation in another clinical trial or using another drug on compassionate use such as fluvoxamide.
6. Very ill patients with multiple comorbidities where determination of clinical outcome will be difficult as judged by the attending physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard of care plus placebo arm; Will contain standard of care plus placebo	Drug: COVIDEX; COVIDEXTm is a prepared plant extract of Zanthoxylum and Warbugia species that is reported to have antiviral agents, one of which berberine with in vitro activity against SARS COV-2, the causative agent for COVID-19 disease. Others constituents in COVIDEX include alkaloids, sponins, reducing sugars and acidic compounds. IT is given either 2 drops nasally plus 6 drops orally or 6 oral drops only of COVIDEXTm three times daily for 7 days.
Experimental: Stanadard of care plus COVIDEX arm; Will contain the standard of care plus the intervention given for 3 times daily for seven days	Drug: COVIDEX; COVIDEXTm is a prepared plant extract of Zanthoxylum and Warbugia species that is reported to have antiviral agents, one of which berberine with in vitro activity against SARS COV-2, the causative agent for COVID-19 disease. Others constituents in COVIDEX include alkaloids, sponins, reducing sugars and acidic compounds. IT is given either 2 drops nasally plus 6 drops orally or 6 oral drops only of COVIDEXTm three times daily for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety primary outcome	Incidence of severe adverse events of grade 3 and above Minimum score: 0, Maximum score: 4. The higher the score, the worse is the adverse event	Daily for 30 days
Efficacy primary outcome:	Clinical recovery as measured by the WHO COVID ordinal improvement score Minimum score:0, Maximum score: 8. The higher the score, the worse is the clinical recovery	Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 antigen present in the nasopharynx	SARS-CoV-2 antigen present in the nasopharynx	Day 8 and day 14
SARS-CoV-2 viral load in the nasopharynx as measured by the CT values	SARS-CoV-2 viral load in the nasopharynx as measured by the CT values	Day 8 and day 14

Collaborators and Investigators

• Sponsor: Makerere University
• Collaborators: Mbarara University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COVIDEX
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: SBS-2022-129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No