BCG Vaccination for Healthcare Workers in COVID-19 Pandemic

January 24, 2022 updated by: TASK Applied Science

Reducing Morbidity and Mortality in Health Care Workers Exposed to SARS-CoV-2 by Enhancing Non-specific Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial

A novel betacoronavirus, SARS-CoV-2, is spreading rapidly throughout the world. A large epidemic in South Africa may overwhelm available hospital capacity and healthcare resources which would be worsened by absenteeism of healthcare workers and other frontline staff (HCW). Strategies to prevent morbidity and mortality of HCW are desperately needed to safeguard continuous patient care. Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis (TB), with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, with reported morbidity and mortality reductions as high as 70%. We hypothesize that a BCG vaccination may reduce the morbidity and mortality of healthcare workers during the COVID-19 outbreak in South Africa.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Morbidity and mortality attributable to COVID-19 is devastating global health systems and economies. Bacillus Calmette Guérin (BCG) vaccination has been in use for many decades to prevent severe forms of tuberculosis in children. Studies have also shown a combination of improved long-term innate or trained immunity (through epigenetic reprogramming of myeloid cells) and adaptive responses after BCG vaccination, which leads to non-specific protective effects in adults. Observational studies have shown that countries with routine BCG vaccination programs have significantly less reported cases and deaths of COVID-19, but such studies are prone to significant bias and need confirmation. To date, in the absence of direct evidence, WHO does not recommend BCG for the prevention of COVID-19.

This project aims to investigate in a timely manner whether and why BCG-revaccination can reduce infection rate and/or disease severity in health care workers during the SARS-CoV-2 outbreak in South Africa. These objectives will be achieved with a blinded, randomised controlled trial of BCG revaccination versus placebo in exposed front-line staff in hospitals in Cape Town. Observations will include the rate of infection with COVID-19 as well as the occurrence of mild, moderate or severe ambulatory respiratory tract infections, hospitalisation, need for oxygen, mechanical ventilation or death. HIV-positive individuals will be excluded. Safety of the vaccines will be monitored. A secondary endpoint is the occurrence of latent or active tuberculosis. Initial sample size and follow-up duration is at least 500 workers and 52 weeks. Statistical analysis will be model-based and ongoing in real time with frequent interim analyses and optional increases of both sample size or observation time, based on the unforeseeable trajectory of the South African COVID-19 epidemic, available funds and recommendations of an independent data and safety monitoring board.

Given the immediate threat of the SARS-CoV-2 epidemic the trial has been designed as a pragmatic study with highly feasible endpoints that can be continuously measured. This allows for the most rapid identification of a beneficial outcome that would lead to immediate dissemination of the results, vaccination of the control group and outreach to the health authorities to consider BCG vaccination for all qualifying health care workers.

Study Type

Interventional

Enrollment (Actual)

1000

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7500
        • TASK Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men and women aged ≥18 years
  • HCW or other frontline staff currently in contact with, or anticipated to be in contact with, patients with SARS-CoV-2 infection.
  • Ability and willingness to provide informed consent.
  • Can be reached by mobile phone for follow-up

Exclusion Criteria:

  • Known allergy to (components of) the BCG vaccine or serious reaction to prior BCG administration.
  • Known active tuberculosis or any other active or uncontrolled condition that, in the opinion of the investigator or designee, makes participation unsafe or makes it difficult to collect follow-up data over the study period.

  • HIV-1 infection

    - NOTE: If evidence of recent HIV negative test is not available, rapid point-of-care testing will be undertaken as part of screening with a separate informed consent process.

  • Symptoms of respiratory tract infection which, in the opinion of the investigator or designee, is likely to interfere with the objectives of the study.

  • Known medical history of any of the following immunocompromised states:

    • Neutropenia (less than 500 neutrophils/mm3)
    • Lymphopenia (less than 400 lymphocytes/mm3)
    • Solid organ or bone marrow transplantation
    • Primary immunodeficiency
    • Active solid or non-solid malignancy or lymphoma within the prior two years
    • Pregnancy and breastfeeding

  • Current treatment with the following medications:

    • Chemotherapy
    • Anti-cytokine therapies
    • Current treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months
    • Any experimental, unproven treatment against SARS-CoV-2 infection or COVID-19 including but not limited to chloroquine, hydroxychloroquine, remdesivir, lopinavir/ritonavir and interferon beta-1a.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bacille Calmette-Guérin (BCG)
Participants will receive an intradermal injection of 0.1ml of the suspended BCG vaccine which accounts for 0.075mg of attenuated Mycobacterium bovis. BCG-Vaccin SSI [Statens Serum Institut], Danish strain 1331.
Biological: Bacille Calmette-Guérin (BCG)
BCG vaccine will be given intradermally in the upper arm after randomization.
Other Names:
  • BCG-Vaccin SSI [Statens Serum Institut], Danish strain 1331
Placebo Comparator: Placebo
The placebo used for this study is 0.9% Sodium Chloride (NaCl). Participants that are randomized to the control arm will receive a placebo injection of 0.1ml 0.9% NaCl, which is the same volume and has the same colour as the suspended BCG vaccine.
Other: Placebo Comparator
Placebo injection will be given intradermally in the upper arm after randomization.
Other Names:
  • 0.9% Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of HCWs hospitalized due to COVID-19 per arm
Time Frame: 52 weeks
To compare the incidence of HCWs hospitalized due to COVID-19 per arm.
52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of SARS-CoV-2 infection per arm
Time Frame: 52 weeks
To determine the incidence of SARS-CoV-2 infection in HCW by molecular or serological testing (as available) at entry, 10, 26 and/or 52 weeks.
52 weeks
Incidence of upper respiratory tract infections per arm
Time Frame: 52 weeks
To compare the incidence of symptoms of upper respiratory tract infection per arm.
52 weeks
Days of unplanned absenteeism due to COVID-19 or any reason per arm
Time Frame: 52 weeks
To compare the number of days of (unplanned) absenteeism because of documented SARS-CoV-2 infection, COVID-19 or any reason per arm.
52 weeks
Incidence of hospitalization for any reason per arm
Time Frame: 52 weeks
To compare the incidence of hospitalization of HCW for any reason per arm.
52 weeks
Incidence of intensive care unit admission per arm
Time Frame: 52 weeks
To compare the incidence of intensive care admission of HCW due to COVID-19 or any reason per arm.
52 weeks
Incidence of death per arm
Time Frame: 52 weeks
To compare the incidence of death of HCW due to COVID-19 or any reason per arm.
52 weeks
Prevalence of latent TB infection
Time Frame: 52 weeks
To describe the prevalence of latent TB infection as determined by interferon gamma release assay (IGRA) at enrolment and at week 52.
52 weeks
Incidence of active TB per arm
Time Frame: 52 weeks
To compare the incidence of active TB of HCW per arm.
52 weeks
Compare the effect of latent TB on morbidity and mortality due to COVID-19 per arm
Time Frame: 52 weeks
To compare the effect of latent TB infection on morbidity and mortality of HCW due to COVID-19 per arm. The risk of morbidity and mortality of latent TB infected individuals is not known, we will examine whether there is a higher risk of disease severity and poor outcomes in this group.
52 weeks
Incidence of treatment related adverse events
Time Frame: 52 weeks
To compare the incidence of grade 2 or higher adverse events and vaccination site reactions per arm.
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TASK Applied Science

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 4, 2020

Primary Completion (Actual)

January 2, 2022

Study Completion (Actual)

January 2, 2022

Study Registration Dates

First Submitted

May 4, 2020

First Submitted That Met QC Criteria

May 6, 2020

First Posted (Actual)

May 7, 2020

Study Record Updates

Last Update Posted (Actual)

January 25, 2022

Last Update Submitted That Met QC Criteria

January 24, 2022

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TASK-008 BCG-CORONA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will only be shared among researchers included in the protocol team at this stage.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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