Trial Outcomes & Findings for Using BCG to Protect Senior Citizens During the COVID-19 Pandemic (NCT NCT04542330)

Last Updated: 2024-08-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1700 participants

Primary outcome timeframe

12 months after inclusion

Results posted on

2024-08-22

Participant Flow

Recruitment took place from September 2020 to December 2021 in Odense, a Danish city of approximately 200,000 inhabitants. Citizens aged 65 years or older, with access to secure electronic mail from the authorities were eligible. Exclusion criteria were known contraindications to BCG vaccination.

Screening details: We screened 1,816 persons for inclusion; 140 fulfilled an exclusion criterion or declined to participate, and 1,676 were included and randomised to BCG (N=838) or placebo (N=838).

Participant milestones

Participant milestones
Measure	BCG-Denmark 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control 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. Saline: 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.
Overall Study STARTED	838	838
Overall Study COMPLETED	838	838
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BCG-Denmark n=838 Participants 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 Participants 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. Saline: 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.	Total n=1676 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=838 Participants	0 Participants n=838 Participants	0 Participants n=1676 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=838 Participants	0 Participants n=838 Participants	0 Participants n=1676 Participants
Age, Categorical >=65 years	838 Participants n=838 Participants	838 Participants n=838 Participants	1676 Participants n=1676 Participants
Age, Continuous	70.5 years n=838 Participants	70.7 years n=838 Participants	70.6 years n=1676 Participants
Sex: Female, Male Female	461 Participants n=838 Participants	461 Participants n=838 Participants	922 Participants n=1676 Participants
Sex: Female, Male Male	377 Participants n=838 Participants	377 Participants n=838 Participants	754 Participants n=1676 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Denmark	838 participants n=838 Participants	838 participants n=838 Participants	1676 participants n=1676 Participants
History of previous BCG vaccination	817 Participants n=838 Participants	818 Participants n=838 Participants	1635 Participants n=1676 Participants
Scar from previous BCG vaccination	717 Participants n=838 Participants	725 Participants n=838 Participants	1442 Participants n=1676 Participants
COVID-19 vaccinated before inclusion	180 Participants n=838 Participants	174 Participants n=838 Participants	354 Participants n=1676 Participants

PRIMARY outcome

Timeframe: 12 months after inclusion

Outcome measures

Outcome measures
Measure	BCG-Denmark n=838 Participants 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 Participants 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. Saline: 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.
Acute Infection Acute infection (composite)	424 Events	469 Events
Acute Infection Infection attended by a physician	212 Events	236 Events
Acute Infection Use of antibiotics	338 Events	341 Events
Acute Infection Hospitalisation due to infection	23 Events	29 Events
Acute Infection Death due to infection	0 Events	0 Events

SECONDARY outcome

Timeframe: 12 months after inclusion

Verified SARS-CoV-2 infection was defined as having a positive SARS-CoV-2 Polymerase Chain Reaction (PCR) test or rapid antigen test.

Outcome measures

Outcome measures
Measure	BCG-Denmark n=838 Participants 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 Participants 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. Saline: 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.
Verified SARS-CoV-2 Infection (First Event)	113 Events	115 Events

SECONDARY outcome

Timeframe: 12 months after inclusion

Self-reported respiratory symptoms were identified from questionnaires, where participants reported having had a respiratory illness such as common cold, influenza, pneumonia, or similar term, and/or reported one or more of the following symptoms: cough, sore throat, runny nose/nasal congestion (common cold symptoms), loss of smell or taste sense, or dyspnoea, with or without general symptoms such as fever, chills, muscle ache, headache, and fatigue (dyspnoea only if in combination with fever). This outcome also included symptoms not requiring medical attention.

Outcome measures

Outcome measures
Measure	BCG-Denmark n=838 Participants 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 Participants 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. Saline: 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.
Self-reported Respiratory Symptoms (Recurrent Events)	957 Events	781 Events

SECONDARY outcome

Timeframe: 12 months from inclusion.

All-cause hospitalisation (first event) included all hospital admissions with overnight stay regardless of duration. Overnight stay was chosen as a condition to exclude contacts such as planned procedures and visits to outpatient clinics.

Outcome measures

Outcome measures
Measure	BCG-Denmark n=838 Participants 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 Participants 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. Saline: 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.
All-cause Hospitalisation (First Event)	81 Events	73 Events

Adverse Events

BCG-Denmark

Serious events: 78 serious events

Other events: 52 other events

Deaths: 1 deaths

Control

Serious events: 63 serious events

Other events: 8 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	BCG-Denmark n=838 participants at risk 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 participants at risk 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. Saline: 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.
General disorders Vaccination site reactions	6.2% 52/838 • Number of events 52 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.95% 8/838 • Number of events 8 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.

Additional Information

Professor Christine Stabell Benn

University of Southern Denmark

Phone: +45 25883964

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	BCG-Denmark n=838 participants at risk 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. BCG-Denmark: Mycobacterium bovis BCG live attenuated BCG-Denmark vaccine (AJ Vaccines, Copenhagen, Denmark) administered by intradermal injection in the left deltoid region.	Control n=838 participants at risk 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. Saline: 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms	0.60% 5/838 • Number of events 6 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.95% 8/838 • Number of events 8 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Vascular disorders Vascular	0.84% 7/838 • Number of events 7 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.84% 7/838 • Number of events 9 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Surgical and medical procedures Procedures	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.12% 1/838 • Number of events 1 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
General disorders General disorders	0.95% 8/838 • Number of events 8 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.95% 8/838 • Number of events 8 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Respiratory, thoracic and mediastinal disorders Respiratory	0.24% 2/838 • Number of events 2 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Psychiatric disorders Psichiatric disorders	0.12% 1/838 • Number of events 1 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Injury, poisoning and procedural complications Injuries	1.2% 10/838 • Number of events 10 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.36% 3/838 • Number of events 3 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Cardiac disorders Cardiac disorders	2.3% 19/838 • Number of events 22 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	2.1% 18/838 • Number of events 20 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Nervous system disorders Neurological disorders	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.12% 1/838 • Number of events 1 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Eye disorders Eye disorders	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.24% 2/838 • Number of events 2 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Gastrointestinal disorders Gastrointestinal disorders	0.95% 8/838 • Number of events 8 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.84% 7/838 • Number of events 9 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Hepatobiliary disorders Hepatobiliary disorders	0.24% 2/838 • Number of events 2 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Renal and urinary disorders Renal disorders	0.24% 2/838 • Number of events 2 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.12% 1/838 • Number of events 1 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Musculoskeletal and connective tissue disorders Musculoskeletal disorders	0.24% 2/838 • Number of events 2 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Infections and infestations Infections	2.1% 18/838 • Number of events 20 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	1.3% 11/838 • Number of events 14 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.
Metabolism and nutrition disorders Metabolic	0.00% 0/838 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.	0.12% 1/838 • Number of events 1 • 12 months Adverse events were registered within 14 days of randomisation. Serious adverse events until end of trial. Participants could report adverse events via the biweekly electronic questionnaires or directly to the investigators at all times during the trial.