Respiratory Tract InfectionsPhase 4BCG-PRIMENCT04537663
Prevention Of Respiratory Tract Infection And Covid-19 Through BCG Vaccination In Vulnerable Older Adults
A Phase 4 study testing Bacille Calmette-Guérin (BCG) in people with Respiratory Tract Infections and Covid19, run by UMC Utrecht at 20 sites in Netherlands.
Trial summary
On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Respiratory Tract Infections, Covid19
- What is being tested?
- Bacille Calmette-Guérin (BCG)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6,112 participants
- Where
- 20 sitesNetherlands
- Study dates
- 7 Sep 2020to 8 Jul 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥60 years
- Having a chronic disease or having undergone major surgery
- Meeting at least one of the following criteria:
- 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.
- Visiting a medical outpatient clinic
- Attending the thrombosis care service
Who cannot join
- 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:
- known infection by the human immunodeficiency virus (HIV-1);
- neutropenic with less than 500 neutrophils/mm3;
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- solid organ transplantation;
- bone marrow transplantation;
- hematological malignancy;
- chemo-, radio- or immunotherapy for solid organ malignancy in the past 6 months;
- primary immunodeficiency;
- severe lymphopenia with less than 400 lymphocytes/mm3;
- 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, or probable use of oral or intravenous steroids in the following four weeks
- Known history of a positive Mantoux or active TB; prior BCG vaccination is NOT an exclusion criterion.
- Born in a country with high incidence of TB; a list of non-eligible countries will be created by the trial steering committee prior to the first enrolment.
- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Netherlands20 sites
Meander Medical Center
Amersfoort
Amsterdam University Medical Center
Amsterdam
OLVG
Amsterdam
Rijnstate hospital
Arnhem
Amphia hospital
Breda
Catharina hospital
Eindhoven
Zuyderland Hospital
Geleen
Martini hospital
Groningen
University Medical Center Groningen
Groningen
Leiden University Medical Center
Leiden
Maastricht University Medical Center
Maastricht
St. Antonius hospital
Nieuwegein
Canisius-Wilhelmina Hospital
Nijmegen
Radboud University Medical Center
Nijmegen
Erasmus Medical Center
Rotterdam
Ikazia Hospital
Rotterdam
Maasstad Hospital
Rotterdam
Hagahospital
The Hague
Bernhoven hospital
Uden
University Medical Center Utrecht
Utrecht
About this study
Official title: Bacillus Calmette-Guérin Vaccination to Prevent Serious Respiratory Tract Infection and Covid-19 in Vulnerable Elderly - an Adaptive randoMized controllEd Trial
On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. In the Netherlands, although the incidence is currently low due to social distancing measures, recurrence of infections is expected once measures are going to be lifted. Although individuals of any age can acquire SARS-CoV-2, adults of middle and older age are at highest risk for developing severe COVID-19 disease. 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 vulnerable populations are urgently needed. Bacille Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but also induces protection against various respiratory infections, including those with a viral etiology. We hypothesize that BCG vaccination reduces clinically relevant respiratory tract infections requiring medical intervention, including COVID-19, in vulnerable elderly.
The objective of this trial is to determine the impact of BCG vaccination on the incidence of clinically relevant respiratory infections or COVID-19 in vulnerable elderly.
The trial is designed as an adaptive multi-center double-blind randomized placebo-controlled trial. The attempt is to include 5,200 to 7,000 vulnerable elderly, defined as ≥60 years of age being discharged from hospital in the last 6 weeks, or visiting a medical outpatient clinic, thrombosis care services, or chronic renal replacement departments. Patients with contraindications to BCG vaccination as stipulated in the Summary of Product Characteristics (SPC) and patients with a history of COVID-19 will be excluded. Participants will be randomized between intracutaneous administration of BCG vaccine (Danish strain 1331) or placebo (0.1ml 0.9% NaCl) in a 1:1 ratio.The trial has an adaptive primary endpoint. Based on accrual of the two endpoints, the primary endpoint will be either (a) COVID-19 or (b) clinically relevant respiratory tract infection requiring medical intervention, potentially including COVID-19 episodes. The other will be declared secondary endpoint. Other secondary endpoints include: all SARS-CoV-2 infections (including asymptomatic infections), influenza infection, acute respiratory infection (ARI; all infections regardless of medical intervention), ARI-related hospital admission, COVID-19 related hospital admission, pneumonia, mental, physical and social functioning, serious adverse events and adverse events, and death.
- Conditions
- Respiratory Tract Infections, Covid19
- Being tested
- Bacille Calmette-Guérin (BCG), Placebo
- Keywords
- Bacillus Calmette-Guerin
- Medical subject headings
- Respiratory Tract Infections, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bacille Calmette-Guérin (BCG)Drug
Participants in the intervention group will be vaccinated with the licensed BCG vaccine (Danish strain 1331, SSI, Denmark) using the standard vaccination technique for this vaccine (intradermal injection in the left upper arm).
PlaceboDrug
Intradermal injection of sterile 0.9% NaCl.
| Study group | Role | What they receive |
|---|---|---|
| Bacille Calmette-Guérin (BCG) | Experimental | Intradermal injection of BCG-Vaccine SSI [Statens Serum Institut]) - Danish strain 1331. Receives: Drug: Bacille Calmette-Guérin (BCG) |
| Placebo | Placebo comparator | Intradermal injection of sterile 0.9% NaCl. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The trial has an adaptive primary endpoint. Based on predefined objective and quantitative criteria the primary endpoint will be either a clinically relevant respiratory tract infection, or COVID-19.
Clinically relevant relevant respiratory tract infection is composed of clinical symptoms in combination with the need for medical intervention. Exact criteria for clinically relevant respiratory tract infection and COVID-19 are described in the protocol.
A blinded adjudication committee will determine the status of the primary endpoints of all participants with a potential primary endpoint, based on information provided in a standardized narrative using data reported by the participant and from GP and hospital medical records when relevant. For detection of ARI, symptoms are checked on a weekly (from week 1-4) or bi-weekly basis (from week 4 onward).
Measured: 180 days
Secondary outcomes (14)
Cumulative incidence of SARS-CoV-2 infection (irrespective the presence of symptoms)
Cumulative incidence of SARS-CoV-2 infection regardless of symptomatology defined as having had COVID-19 as described under primary endpoints above and/or SARS-CoV-2 positive test in real time as part of the test-and-trace program of the Dutch government and/of documented SARS-CoV-2 seroconversion at 6 months. Seroconversion will be defined as antibody-positive at 6 months but negative at baseline.
Measured: 180 days
Cumulative incidence of asymptomatic, mild/moderate, and severe (requiring hospitalization) SARS-CoV-2 infection.
Measured: 180 days
Influenza infection
Defined as either of 1) ARI + microbiological evidence of influenza infection, 2) seroconversion of influenza between enrolment and month 6.
Measured: 180 days
An acute respiratory tract infection
Meeting the definition stated in the primary outcome. Irrespective of requiring an intervention.
Measured: 180 days
Medically attended acute respiratory tract infection
Meeting the definition stated in the primary outcome including the requirement of an intervention.
Measured: 180 days
Acute respiratory tract infection related hospital admission
Meeting the definition stated in the primary outcome including the need of hospitalization.
Measured: 180 days
Pneumonia diagnosed by a GP or medical specialist
Measured: 180 days
Functioning in daily activities
Using the Katz Activities of Daily Living (ADL) scale, from A (fully independent) to G (dependent in feeding, continence, transferring, going to toilet, dressing, and bathing)
Measured: 180 days
Serious adverse events and adverse events.
Measured: 180 days
Major cardiovascular events
Measured: 180 days
All cause 6-month mortality
Measured: 180 days
History of falls
Measured: 180 days
Quality of life using the EQ5D quality of life instrument
Using the EQ5D quality of life instrument, with questions on 4 domains (mobility, self-care, usual activities, pain discomfort) and the percepted health of the participant with 100 meaning the best health you can imagine, and 0 meaning the worst health you can imagine
Measured: 180 days
Activities in daily living
Using the 6-item Lawton Activities of Daily Living questionnaire, with scores ranging from 0 (low function, dependent) to 8 (high function, independent) for women (0 through 5 for men)
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start7 Sep 2020
- Primary completion8 Jul 2021
- Study completion8 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Tract InfectionsStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6,112 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, MJM Bonten, UMC Utrecht
- Investigators
- Marc Bonten, MD, PhD., Principal investigator, UMC UtrechtMihai Netea, MD, PhD, Study chair, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04537663
- Sponsor's protocol ID
- BCG-PRIME
- Acronym
- BCG-PRIME
- Status last verified
- Sep 2022
- First submitted
- 28 Aug 2020
- Last updated
- 23 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bacillus Calmette-Guérin Vaccination to Prevent Serious Respiratory Tract Infection and Covid-19 in Vulnerable Elderly - an Adaptive randoMized controllEd Trial
- ClinicalTrials.gov ID
- NCT04537663
- Acronym / sponsor ID
- BCG-PRIME / BCG-PRIME
- Conditions
- Respiratory Tract Infections, Covid19
- Keywords
- Bacillus Calmette-Guerin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6,112 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- 7 Sep 2020 (actual)
- Primary completion
- 8 Jul 2021 (actual)
- Study completion
- 8 Jul 2021 (actual)
- First posted
- 3 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. In the Netherlands, although the incidence is currently low due to social distancing measures, recurrence of infections is expected once measures are going to be lifted. Although individuals of any age can acquire SARS-CoV-2, adults of middle and older age are at highest risk for developing severe COVID-19 disease. 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 vulnerable populations are urgently needed. Bacille Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but also induces protection against various respiratory infections, including those with a viral etiology. We hypothesize that BCG vaccination reduces clinically relevant respiratory tract infections requiring medical intervention, including COVID-19, in vulnerable elderly.
The objective of this trial is to determine the impact of BCG vaccination on the incidence of clinically relevant respiratory infections or COVID-19 in vulnerable elderly.
The trial is designed as an adaptive multi-center double-blind randomized placebo-controlled trial. The attempt is to include 5,200 to 7,000 vulnerable elderly, defined as ≥60 years of age being discharged from hospital in the last 6 weeks, or visiting a medical outpatient clinic, thrombosis care services, or chronic renal replacement departments. Patients with contraindications to BCG vaccination as stipulated in the Summary of Product Characteristics (SPC) and patients with a history of COVID-19 will be excluded. Participants will be randomized between intracutaneous administration of BCG vaccine (Danish strain 1331) or placebo (0.1ml 0.9% NaCl) in a 1:1 ratio.The trial has an adaptive primary endpoint. Based on accrual of the two endpoints, the primary endpoint will be either (a) COVID-19 or (b) clinically relevant respiratory tract infection requiring medical intervention, potentially including COVID-19 episodes. The other will be declared secondary endpoint. Other secondary endpoints include: all SARS-CoV-2 infections (including asymptomatic infections), influenza infection, acute respiratory infection (ARI; all infections regardless of medical intervention), ARI-related hospital admission, COVID-19 related hospital admission, pneumonia, mental, physical and social functioning, serious adverse events and adverse events, and death.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bacille Calmette-Guérin (BCG) | Experimental | Drug: Bacille Calmette-Guérin (BCG)Intradermal injection of BCG-Vaccine SSI [Statens Serum Institut]) - Danish strain 1331. |
| Placebo | Placebo comparator | Drug: PlaceboIntradermal injection of sterile 0.9% NaCl. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥60 years
- Having a chronic disease or having undergone major surgery
- Meeting at least one of the following criteria:
Key exclusion criteria (19 listed)
- 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:
- Known history of a positive Mantoux or active TB; prior BCG vaccination is NOT an exclusion criterion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bacille Calmette-Guérin (BCG)Participants in the intervention group will be vaccinated with the licensed BCG vaccine (Danish strain 1331, SSI, Denmark) using the standard vaccination technique for this vaccine (intradermal injection in the left upper arm). | Drug | Bacille Calmette-Guérin (BCG) |
| PlaceboIntradermal injection of sterile 0.9% NaCl. | Drug | Placebo |
Primary outcome
The trial has an adaptive primary endpoint. Based on predefined objective and quantitative criteria the primary endpoint will be either a clinically relevant respiratory tract infection, or COVID-19.
Time frame: 180 days
Clinically relevant relevant respiratory tract infection is composed of clinical symptoms in combination with the need for medical intervention. Exact criteria for clinically relevant respiratory tract infection and COVID-19 are described in the protocol. A blinded adjudication committee will determine the status of the primary endpoints of all participants with a potential primary endpoint, based on information provided in a standardized narrative using data reported by the participant and from GP and hospital medical records when relevant. For detection of ARI, symptoms are checked on a weekly (from week 1-4) or bi-weekly basis (from week 4 onward).
14 secondary outcomes
Cumulative incidence of SARS-CoV-2 infection (irrespective the presence of symptoms)
Time frame: 180 days
Cumulative incidence of asymptomatic, mild/moderate, and severe (requiring hospitalization) SARS-CoV-2 infection.
Time frame: 180 days
Influenza infection
Time frame: 180 days
An acute respiratory tract infection
Time frame: 180 days
Medically attended acute respiratory tract infection
Time frame: 180 days
Acute respiratory tract infection related hospital admission
Time frame: 180 days
Pneumonia diagnosed by a GP or medical specialist
Time frame: 180 days
Functioning in daily activities
Time frame: 180 days
Serious adverse events and adverse events.
Time frame: 180 days
Major cardiovascular events
Time frame: 180 days
All cause 6-month mortality
Time frame: 180 days
History of falls
Time frame: 180 days
Quality of life using the EQ5D quality of life instrument
Time frame: 180 days
Activities in daily living
Time frame: 180 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Bonten, MD, PhD. principal investigator
UMC Utrecht
Mihai Netea, MD, PhD study chair
Radboud University Medical Center
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bacille Calmette-Guérin (BCG) in people with Respiratory Tract Infections and Covid19, run by UMC Utrecht at 20 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The trial has an adaptive primary endpoint. Based on predefined objective and quantitative criteria the primary endpoint will be either a clinically relevant respiratory tract infection, or COVID-19. (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.