Bacillus Calmette-guérin Vaccination to Prevent Infections of the Elderly (ACTIVATE)
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|ClinicalTrials.gov Identifier: NCT03296423|
Recruitment Status : Completed
First Posted : September 28, 2017
Last Update Posted : January 11, 2021
|Condition or disease||Intervention/treatment||Phase|
|Infection Hospitalization Mortality||Biological: Vaccination Biological: Placebo||Phase 4|
In an era of antimicrobial resistance, where the already existing antimicrobials are not sufficient, the development of new strategies for the prevention and treatment of infections is of great interest. This approach becomes more and more mandatory in our current era of the financial crisis where bacterial infections by multidrug-resistant emerge and impose heavily on the financial burden of the disease. These infections occur more frequently among elderly patients leading to prolonged hospitalization where unfavorable outcome is not infrequent1. Vaccination is the traditional approach of infection prevention. A classic example focusing on the need to prevent morbid re-infection is vaccination with pneumococcal vaccine the incidence of pneumococcal pneumonia and bacteremia is enormously increasing among the elderly2. The principle of vaccination is to develop memory B-lymphocytes so that early and adequate antibody titers are produced upon re-exposure to the same antigen. This is called the memory function of the adaptive immune system.
Well before adaptive immunity develops proper recognition of a bacterial pathogen is done through binding of well-preserved structures known as pathogen-associated molecular patterns (PAMPs) on pattern-recognition receptors (PRRs) of the innate immune system and mainly of blood monocytes and tissue macrophages. Through a series of experiments in cell systems and animals, it was found that exposure of macrophages to small amounts of PAMPs like the β-glucan of Candida albicans and constituents of Mycobacterium tuberculosis may prevent death upon re-exposure to lethal bacterial challenges like C.albicans and Staphylococcus aureus3-6. Initial exposure to small amounts of PAMPs leads to epigenetic changes that induce the capacity of macrophages and monocytes to produce high amounts of pro-inflammatory cytokines like tumour necrosis factor-alpha (TNFα) and interferon-gamma (IFNγ) that clear efficiently the pathogen3. This enhancement of the immune cells reaction after appropriate priming to stimuli totally different from the initial ones is called trained immunity and it could be a potential pathway of preventing serious infections without having severe adverse effects.
The concept has also been tested in healthy volunteers that were vaccinated with placebo or BCG (Baccillus Calmette Guérin) vaccine. These volunteers were injected 14 days latter a tri-valent influenza A vaccine. Volunteers previous vaccinated by BCG developed significantly greater titers against hemagglutinin A of the influenza A virus whereas their circulating monocytes were more potent for the production of IFNγ7. Finally, a small study has recently reported that BCG vaccination of the elderly may protect against infections8, but larger studies are necessary to confirm these findings. This generates hopes that vaccination by BCG may increase immune resistance and/or tolerance of elderly patients upon exposure to bacterial infections.
This generates hopes that vaccination by BCG may increase immune tolerance of elderly patients upon exposure to bacterial diseases.
The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of elderly patients with BCG vaccine may modulate their disease susceptibility for bacterial diseases. This will be validated using both clinical and immunological criteria.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Patients vaccinated with placebo or BCG|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized Clinical Trial for Enhanced Trained Immune Responses Through Bacillus Calmette-guérin Vaccination to Prevent Infections of the Elderly|
|Actual Study Start Date :||September 21, 2017|
|Actual Primary Completion Date :||August 31, 2020|
|Actual Study Completion Date :||November 30, 2020|
Placebo Comparator: Placebo
One intradermal injection of 0.1ml of sodium chloride 0.9%
Patients discharged from hospital will be vaccinated with one intradermal injection of 0.1ml of sodium chloride 0.9%
Other Name: Saline
Active Comparator: Vaccination
One intradermal injection of 0.1ml of BCG (BCG vaccine Bulgaria strain 1331; Intervax)
Patients discharged from hospital will be vaccinated with one intradermal injection of 0.1ml of BCG vaccine
- Time to first infection [ Time Frame: 12 months ]The time interval to the first infection post hospital discharge between the two groups of treatment.
- Hospitalization [ Time Frame: Month 12 ]The rate of hospitalizations will be compared between the two groups of treatment
- Time to first infection or sepsis episode [ Time Frame: Month 12 ]The time to first infection or sepsis episode will be compared between the two groups of treatment
- Total number of infections [ Time Frame: Month 12 ]The total number of infections will be compared between the two groups of treatment
- Time to first hospitalization [ Time Frame: Month 12 ]The time to first hospitalization will be compared between the two groups of treatment
- Number of antibiotic administrations [ Time Frame: Month 12 ]The number of antibiotic administrations will be compared between the two groups of treatment
- Mortality [ Time Frame: Month 12 ]Mortality will be compared between the two groups of treatment
- Cytokine stimulation [ Time Frame: Month 3 ]Cytokine stimulation from peripheral blood monuclear cells will be compared between the two groups of treatment
- Epigenetic changes [ Time Frame: Month 3 ]Epigenetic changes of circulating monocytes will be compared between the two groups of treatment
- Cost of treatment [ Time Frame: Month 12 ]The effect of BCG vaccination on cost of treatment for infections will be compared between the two groups of treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03296423
|4th Department of Internal Medicine, ATTIKON University Hospital|
|Athens, Attiki, Greece, 12462|
|Principal Investigator:||Antonios Papadopoulos, MD, PhD||National and Kapodistrian University of Athens|