Clinical trial NCT04417335: Reducing COVID-19 Related Hospital Admission in Elderly by BCG Vaccination
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: COVID-19
Keywords: BCG
Bacille Calmette-Guérin
COVID-19
SARS-CoV-2
trained immunity
off-target effects
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2020-06-04
Enrollment: 2014
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-controlled adaptive multi-centre randomized controlled trial
Primary purpose: PREVENTION

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: SARS-CoV-2 related hospital admission
timeFrame: Maximum of 1 year
Secondary outcomes:
measure: the duration of hospital admission due to documented COVID-19
timeFrame: Maximum of 1 year
measure: the cumulative incidence of documented SARS-CoV-2 infection
timeFrame: Maximum of 1 year
measure: the cumulative incidence of self-reported acute respiratory symptoms or fever
timeFrame: Maximum of 1 year
measure: the cumulative incidence of death due to documented SARS-CoV-2 infection
timeFrame: 1 year
measure: the cumulative incidence of hospital admission for any reason
timeFrame: Maximum of 1 year
measure: the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection
timeFrame: Maximum of 1 year
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University
state: Gelderland
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References:
citation: 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.