BCG Vaccination for Healthcare Workers in COVID-19 Pandemic

NCT04379336 | Completed Phase 3 DMC

• 1 other identifier: TASK-008 BCG-CORONA
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COVID-19; Sars-CoV2

Keywords

Blinded; Randomized controlled; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Incidence of HCWs hospitalized due to COVID-19 per arm

  To compare the incidence of HCWs hospitalized due to COVID-19 per arm.

  52 weeks

Secondary Outcomes (10)

• Incidence of SARS-CoV-2 infection per arm

  52 weeks

• Incidence of upper respiratory tract infections per arm

  52 weeks

• Days of unplanned absenteeism due to COVID-19 or any reason per arm

  52 weeks

• Incidence of hospitalization for any reason per arm

  52 weeks

• Incidence of intensive care unit admission per arm

  52 weeks

Study Arms (2)

Bacille Calmette-Guérin (BCG)

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

Bacille Calmette-Guérin (BCG) BIOLOGICAL

BCG vaccine will be given intradermally in the upper arm after randomization.

Also known as: BCG-Vaccin SSI [Statens Serum Institut], Danish strain 1331

Bacille Calmette-Guérin (BCG)

Placebo Comparator OTHER

Placebo injection will be given intradermally in the upper arm after randomization.

Also known as: 0.9% Sodium Chloride

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• TASK Applied Science: lead

Study Sites (1)

TASK Foundation

Cape Town, Western Cape, 7500, South Africa

Location

Related Publications (4)

• Netea MG, Schlitzer A, Placek K, Joosten LAB, Schultze JL. Innate and Adaptive Immune Memory: an Evolutionary Continuum in the Host's Response to Pathogens. Cell Host Microbe. 2019 Jan 9;25(1):13-26. doi: 10.1016/j.chom.2018.12.006.

  PMID: 30629914 BACKGROUND

• Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17537-42. doi: 10.1073/pnas.1202870109. Epub 2012 Sep 17.

  PMID: 22988082 BACKGROUND

• van Wijk RC, Mockeliunas L, Upton CM, Peter J, Diacon AH, Simonsson USH. Seasonal influence on respiratory tract infection severity including COVID-19 quantified through Markov Chain modeling. CPT Pharmacometrics Syst Pharmacol. 2023 Sep;12(9):1250-1261. doi: 10.1002/psp4.13006. Epub 2023 Jul 10.

  PMID: 37401774 DERIVED

• Upton CM, van Wijk RC, Mockeliunas L, Simonsson USH, McHarry K, van den Hoogen G, Muller C, von Delft A, van der Westhuizen HM, van Crevel R, Walzl G, Baptista PM, Peter J, Diacon AH; BCG CORONA Consortium. Safety and efficacy of BCG re-vaccination in relation to COVID-19 morbidity in healthcare workers: A double-blind, randomised, controlled, phase 3 trial. EClinicalMedicine. 2022 Jun;48:101414. doi: 10.1016/j.eclinm.2022.101414. Epub 2022 May 12.

  PMID: 35582122 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Efficacy will be determined based on documented SARS-CoV-2 infection and incidence of hospitalization. The analysis will be an intention-to-treat analysis with estimation of hazard ratio between the two arms using a Cox proportional hazard model. Adverse events will be summarized using descriptive statistics per study arm. The analysis will be a model-based analysis of cumulative data on general health status as a function of risk factors, treatment arm and time.

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 7, 2020
• Study Start: May 4, 2020
• Primary Completion: January 2, 2022
• Study Completion: January 2, 2022
• Last Updated: January 25, 2022

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)