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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Biological: BCG vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo-controlled adaptive multi-centre randomized controlled trial
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCG, Bacille Calmette-Guérin, COVID-19, SARS-CoV-2, trained immunity, off-target effects