Reducing COVID-19 Related Hospital Admission in Elderly by BCG Vaccination

Reducing Hospital Admission of Elderly in SARS-CoV-2 Pandemic Via the Induction of Trained Immunity by Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial

Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease severity in elderly people, who are known to be at increased risk of illness and death from SARS-CoV-2 infection.

Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Biological: Placebo; Biological: BCG vaccine

Detailed Description

On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. The number of confirmed cases continues to rise, leading to significant morbidity and mortality worldwide. Although individuals of any age can acquire SARS-CoV-2, adults of middle age and older are most commonly affected. Moreover, recent reports demonstrate that mortality rates rise significantly among patients 60 years and older. Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences in elderly are desperately needed. Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination may reduce hospital admission and improve the clinical course of symptoms of elderly people during the SARS-CoV-2 outbreak. Primary objective: To reduce hospital admission of community dwelling older persons during the pandemic of SARS-CoV-2. Secondary objective: To reduce disease severity, the duration of hospital admission, ICU admission, or death in elderly during the pandemic of SARS-CoV-2.

Study design: A placebo-controlled adaptive multi-centre randomized controlled trial.

Study population: Elderly people (≥ 60 years of age). Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 2014
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • UMC Utrecht
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (≥ 60 years)

Exclusion Criteria:

• Fever (>38 ºC) within the past 24 hours
• Suspicion of current active viral or bacterial infection
• Expected vaccination during the first three months of the study period
• Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic subjects with less than 500 neutrophils/mm3; c) subjects with solid organ transplantation; d) subjects with bone marrow transplantation; e) subjects under chemotherapy; f) subjects with primary immunodeficiency; g) severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any immunosuppressant drugs such as anti-cytokine therapies, and treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months, or probable use of oral or intravenous steroids in the following four weeks.
• Active solid or non-solid malignancy or lymphoma within the prior two years
• Active participation in another research study that involves BCG administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment; BCG vaccine (Danish strain 1331, SSI, Denmark)	Biological: BCG vaccine; Bacille Calmette-Guérin is a live attenuated strain of Mycobacterium bovis developed in 1921 to prevent tuberculosis and other mycobacterial related infections.
PLACEBO_COMPARATOR: Placebo; 0.9% NaCl	Biological: Placebo; 0.9% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SARS-CoV-2 related hospital admission	Maximum of 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
the duration of hospital admission due to documented COVID-19	Maximum of 1 year
the cumulative incidence of documented SARS-CoV-2 infection	Maximum of 1 year
the cumulative incidence of self-reported acute respiratory symptoms or fever	Maximum of 1 year
the cumulative incidence of death due to documented SARS-CoV-2 infection	1 year
the cumulative incidence of hospital admission for any reason	Maximum of 1 year
the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection	Maximum of 1 year

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Publications and helpful links

General Publications

• Moorlag SJCFM, Taks E, Ten Doesschate T, van der Vaart TW, Janssen AB, Muller L, Ostermann P, Dijkstra H, Lemmers H, Simonetti E, Mazur M, Schaal H, Ter Heine R, van de Veerdonk FL, Bleeker-Rovers CP, van Crevel R, Ten Oever J, de Jonge MI, Bonten MJ, van Werkhoven CH, Netea MG. Efficacy of BCG Vaccination Against Respiratory Tract Infections in Older Adults During the Coronavirus Disease 2019 Pandemic. Clin Infect Dis. 2022 Aug 24;75(1):e938-e946. doi: 10.1093/cid/ciac182.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 16, 2020
• Primary Completion (ANTICIPATED): May 1, 2021
• Study Completion (ANTICIPATED): May 1, 2021

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: June 3, 2020
• First Posted (ACTUAL): June 4, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; trained immunity; BCG; Bacille Calmette-Guérin; off-target effects
• 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; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; BCG Vaccine
• Other Study ID Numbers: NL73430.091.20; 2020-001591-15 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No