Long Term Effects of BCG Vaccination on Infectious and Immune Mediated Diseases

NCT ID: NCT05387655

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 4292 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-20
• Study Completion Date: 2027-06-20

Brief Summary

Rationale: The effects of BCG vaccination have been only sporadically studied in the elderly, and the long-term effects of the vaccination have not been studied until now. There is evidence that BCG vaccination beneficially influences susceptibility and severity of infectious and inflammatory diseases; however, the specifics, extent and duration of these effects are not known yet. With this observational study we would like to determine the extent of these effects in the elderly.

Objective: To identify any long term effects of BCG vaccination on the incidence of infectious and inflammatory diseases may have in the elderly

Study design: Cohort study with a duration of 5 years

Study population: Older adults who participated in two large randomized BCG vaccination trials in 2020/2021 (BCG-CORONA-OUDEREN, BCG-PRIME), who have consented to be contacted for further studies

Main study parameters/endpoints:

The incidence of infectious and inflammatory diseases in the placebo- vs. BCG-vaccinated individuals

Conditions

BCG Vaccination Reaction; Infections; Inflammation; COVID-19

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

BCG vaccination

People who received a BCG vaccination in the prior BCG-CORONA-ELDERLY or BCG-PRIME study

BCG

Intervention Type: BIOLOGICAL

BCG vaccination

Placebo vaccination

People who received a placebo vaccination in the prior BCG-CORONA-ELDERLY or BCG-PRIME study

Placebo vaccine

Intervention Type: BIOLOGICAL

Placebo vaccination

Interventions

BCG

BCG vaccination

Intervention Type: BIOLOGICAL

Placebo vaccine

Placebo vaccination

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Completed participation in the BCG-CORONA-ELDERLY or BCG-PRIME study
• Given consent to be approached for further studies

• Age ≥60 years
• Meeting at least one of the following criteria:

1. Having a chronic somatic disease*

2. Having undergone major surgery**

3. Planned to be discharged from the hospital or discharged from the hospital less than 6 weeks ago; a hospital admission is defined as an overnight stay. Departments of interest are those that in the opinion of the principle investigator admit mostly vulnerable elderly and include but are not limited to: cardiology, pulmonology, internal medicine, neurology.

4. Attending the thrombosis care service * Chronic somatic diseases do not include risk factors such as hypertension or obesity unless the participant receives medication targeted against the risk factor.

• Major surgery is any invasive operative procedure in which a more extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major

• Adult (≥ 60 years)
• Written informed consent

Exclusion Criteria

• Has received a BCG vaccination after the BCG-CORONA-ELDERLY or BCG-PRIME study

• Fever (>38 ºC) within the past 24 hours
• Suspicion of current active viral or bacterial infection; the requirement to finish an antibiotic course upon discharge is not an exclusion criterion when the infection is controlled in the opinion of the attending physician
• Vaccination with live vaccine in the past four weeks or planned vaccination with live vaccine during the next four weeks
• Severely immunocompromised participants. This exclusion category comprises:

1. known infection by the human immunodeficiency virus (HIV-1);

2. neutropenic with less than 500 neutrophils/mm3;

3. solid organ transplantation;

4. bone marrow transplantation;

5. hematological malignancy;

6. chemo-, radio- or immunotherapy for solid organ malignancy in the past 6 months;

7. primary immunodeficiency;

8. severe lymphopenia with less than 400 lymphocytes/mm3;

9. treatment with any immunosuppressant drugs such as anti-cytokine therapies, and treatment with oral or intravenous steroids defined as daily doses of >10 mg/day or a cumulative dose of >700 mg prednisone or equivalent for other corticosteroids in the three months prior to enrolment, or probable use of oral or intravenous steroids in the following four weeks;

10. receiving chronic renal replacement therapy.

• Known history of a positive Mantoux or active TB; prior BCG vaccination or a positive Mantoux test after BCG vaccination without confirmation of TB are NOT an exclusion criterion.
• Born in a country with high incidence of TB (see supplement B)
• Active participation in another research study that involves BCG administration
• History of documented COVID-19 (self-reported by the participant: either confirmed by a microbiological test or with clinical diagnosis during hospitalization)
• Not able to perform the study procedures as judged by the attending physician
• Legally incapacitated or unwilling to provide informed consent

• 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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

UMC Utrecht

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radboud university medical center

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

2022-13462

Identifier Type: -

Identifier Source: org_study_id