Using BCG to Protect Senior Citizens During the COVID-19 Pandemic

NCT04542330 | Completed Phase 3 Results DMC

• 1 other identifier: BCG-DENMARK-SENIOR
• Study Type: interventional
• Target: 1,700
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The virus SARS-CoV-2 has spread rapidly throughout the world. Seniors are at high risk of severe COVID-19 when infected. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other infections; significant reductions in morbidity and mortality have been reported, and a plausible immunological mechanism has been identified: "trained innate immunity". The investigators hypothesize that BCG vaccination can reduce the risk of COVID-19 and other infections among senior citizens during the COVID-19 pandemic. Objectives: Primary objective: To reduce senior citizens' risk of acute infection during the COVID-19 pandemic. Secondary objectives: To reduce senior citizens' risk of SARS-CoV-2 infection during the COVID-19 pandemic. To reduce senior citizens' risk of self-reported respiratory illness during the COVID-19 pandemic. Study design: A placebo-controlled randomized trial. Study population: 1900 seniors 65 years of age or above. Intervention: Participants will be randomized 1:1 to intradermal administration of a standard dose of BCG vaccine or placebo (saline). Outcomes: Primary outcome: "Acute infection" identified either by a doctor, antibiotics use, hospitalization, or death due to infection. Secondary outcomes: Verified SARS-CoV-2 infection and self-reported respiratory illness. With an expected incidence of "acute infection" of 20%, the trial can show a 25% risk reduction in the the intervention group versus the placebo group by including a total of 1900 individuals, 950 individuals in each group. Risk for participants and impact: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. If BCG can reduce the risk of acute infection in seniors by 25% it has tremendous public health importance, both during the COVID-19 pandemic and overall.

Conditions

Covid19; Non-specific Effects of Vaccines; Heterologous Immunity; Morbidity; Immunosenescence; Vaccine Preventable Disease

Outcome Measures

Primary Outcomes (1)

• Acute Infection

  The primary outcome was a composite outcome of acute infection (recurrent events) defined as "infection attended by a physician", "use of antibiotics", "hospitalisation due to infection", or "death due to infection". All subcomponents were also analysed separately.

  12 months after inclusion

Secondary Outcomes (3)

• Verified SARS-CoV-2 Infection (First Event)

  12 months after inclusion

• Self-reported Respiratory Symptoms (Recurrent Events)

  12 months after inclusion

• All-cause Hospitalisation (First Event)

  12 months from inclusion.

Study Arms (2)

BCG-Denmark

ACTIVE COMPARATOR

Participants that are randomized to the active comparator arm will receive an adult 0.1 ml dose of BCG vaccine (BCG-Denmark, AJ Vaccines) in the skin covering the left upper deltoid muscle. Each 0.1 ml dose of vaccine contains between 200,000 to 800,000 colony forming units of the live attenuated strain of Mycobacterium bovis (BCG), Danish strain 1331.

Biological: BCG-Denmark

Control

PLACEBO COMPARATOR

Participants randomized to the control group will receive one 0.1 ml dose sterile 0.9 % NaCl by intradermal injection in the left deltoid region.

Biological: Saline

Interventions

BCG-Denmark BIOLOGICAL

Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.

Also known as: BCG-1331, BCG-AJ, BCG-SSI

BCG-Denmark

Saline BIOLOGICAL

Participants randomized to the control group will receive one 0.1 ml dose sterile 0.9 % NaCl by intradermal injection in the left deltoid region.

Also known as: NaCl

Control

Eligibility Criteria

• Age: 65 Years - 110 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet the following criteria: ≥65 years old.

You may not qualify if:

• Known allergy to (components of) the BCG vaccine or serious adverse events in relation to prior BCG administration
• Previous Mycobacterium tuberculosis (M. tuberculosis) infection or known active or latent infection with M. tuberculosis or other mycobacterial species
• Previous confirmed COVID-19 infection
• Fever (\>38 C) within the past 24 hours or suspicion of active viral or bacterial infection
• Vaccination with other live attenuated vaccine within the last 4 weeks
• Subjects with known infection with the human immunodeficiency virus (HIV)
• Subjects with solid organ transplantation or bone marrow transplantation
• Subjects under chemotherapy
• Subjects with primary immunodeficiency
• Treatment with any anti-cytokine therapy within the last year
• Treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months
• Active solid or non-solid malignancy or lymphoma within the prior two years
• Subjects who do not have access to e-Boks.

Sponsors & Collaborators

• Bandim Health Project: lead
• Odense Patient Data Explorative Network: collaborator
• Odense University Hospital: collaborator
• Municipality of Odense: collaborator

Study Sites (1)

Seniorhuset

Odense, 5000, Denmark

Location

Related Publications (2)

• Benn CS, Fisker AB, Rieckmann A, Sorup S, Aaby P. Vaccinology: time to change the paradigm? Lancet Infect Dis. 2020 Oct;20(10):e274-e283. doi: 10.1016/S1473-3099(19)30742-X. Epub 2020 Jul 6.

  PMID: 32645296 BACKGROUND

• Madsen AMR, Gehrt L, Schaltz-Buchholzer F, Moller S, Christiansen R, Schellerup L, Norberg LA, Krause TG, Nielsen S, Bliddal M, Aaby P, Benn CS. Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic: A randomised clinical trial. J Infect. 2024 Dec;89(6):106319. doi: 10.1016/j.jinf.2024.106319. Epub 2024 Oct 17.

  PMID: 39423874 DERIVED

MeSH Terms

Conditions

COVID-19; Vaccine-Preventable Diseases

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

Results Point of Contact

• Title: Professor Christine Stabell Benn
• Organization: University of Southern Denmark

cbenn@health.sdu.dk

+45 25883964

Study Officials

• Anne Marie Rosendahl Madsen, MD

  Bandim Health Project, Department of Clinical Research, Uni. Southern Denmark

  PRINCIPAL INVESTIGATOR

• Christine Stabell Benn, DMSc

  Bandim Health Project, Department of Clinical Research, Uni. Southern Denmark

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be blinded to treatment. The physicians administering the BCG vaccine or placebo will not be blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo-controlled randomized trial.

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 9, 2020
• Study Start: September 15, 2020
• Primary Completion: January 11, 2023
• Study Completion: January 11, 2023
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: When follow-up has been completed and the dataset have been closed
• Access Criteria: Per justified request on email (cbenn@health.sdu.dk)

Locations

DK (1)