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

• ClinicalTrials.gov Identifier: NCT04417335
• Recruitment Status: Unknown
• First Posted: June 4, 2020
• Last Update Posted: June 4, 2020
• Sponsor: Radboud University Medical Center
• Information provided by (Responsible Party): Radboud University Medical Center

Study Description

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).

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: BCG vaccine; Biological: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2014 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: placebo-controlled adaptive multi-centre randomized controlled trial
• Masking: Single (Participant)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: April 16, 2020
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. SARS-CoV-2 related hospital admission [ Time Frame: Maximum of 1 year ]

Secondary Outcome Measures :

1. the duration of hospital admission due to documented COVID-19 [ Time Frame: Maximum of 1 year ]
2. the cumulative incidence of documented SARS-CoV-2 infection [ Time Frame: Maximum of 1 year ]
3. the cumulative incidence of self-reported acute respiratory symptoms or fever [ Time Frame: Maximum of 1 year ]
4. the cumulative incidence of death due to documented SARS-CoV-2 infection [ Time Frame: 1 year ]
5. the cumulative incidence of hospital admission for any reason [ Time Frame: Maximum of 1 year ]
6. the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection [ Time Frame: Maximum of 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Netherlands

Radboud University

Nijmegen, Gelderland, Netherlands, 6525 GA

UMC Utrecht

Utrecht, Netherlands, 3584 CX

Sponsors and Collaborators

Radboud University Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT04417335
• Other Study ID Numbers: NL73430.091.20; 2020-001591-15 ( EudraCT Number )
• First Posted: June 4, 2020
• Last Update Posted: June 4, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Radboud University Medical Center:

BCG; Bacille Calmette-Guérin; COVID-19; SARS-CoV-2; trained immunity; off-target effects

Additional relevant MeSH terms:

COVID-19; BCG Vaccine; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs