BCGPhase 3NCT04461379
Prevention, Efficacy and Safety of BCG Vaccine in COVID-19 Among Healthcare Workers
A Phase 3 study testing BCG vaccine in people with BCG and COVID-19, run by Hospital Universitario Dr. Jose E. Gonzalez at 1 site in Mexico.
Trial summary
In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- What is being tested?
- BCG vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 908 participants
- Where
- 1 siteMexico
- Study dates
- 21 Jul 2020to 1 Jan 2021
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Health workers who are working onsite in patients' areas with COVID-19
- Age > 18 years
- Negative specific IgG and IgM antibodies test result for SARS CoV-2 before the enrollment.
- Provide a signed and dated informed consent form
Who cannot join
- Age <18 years
- Positive test for specific antibodies IgG and IgM antibodies result for SARS Cov-2
- Primary or secondary immunosuppression
- Use of immunosuppression drugs, use of hydroxychloroquine, cloroquine, Azithromycin, Lopinavir/ritonavir, Ivermectin or any other drug used to treat patients COVID-19 before the enrollment.
- Chemotherapy treatment
- Presence of antibodies IgA, IgM, IgG against SARS-CoV-2
Show all 17Show fewer
- Pregnancy or breastfeeding
- Missing informed consent form
- Fever > 38° in the previous 24 hours
- Any BCG vaccine contraindication
- History of previous allergy to the components of the vaccine
- Already part of any other trial
- Previous or active tuberculosis (TB) disease
- Another vaccine administrated 4 months before the start of the trial.
- Any underlying history of malignancy or lymphoma.
- Actual treatment with steroids
- Absence of more than 1 month from the hospital, from the study period.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Hospital Universitario "José E. González"
Monterrey, Nuevo León, 64460
About this study
Official title: Prevention, Efficacy and Safety of BCG Vaccine in COVID-19- Randomized Clinical Trial
In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.
Read the detailed description
The study design is a randomized, double-blinded, placebo-controlled clinical trial.
Age stratified randomization (<45 years and> 45 years) was performed using permuted blocks with allocation concealment.
The sample size is 908 patients. 454 patients in each stratum (227 with placebo and 227 with BCG vaccine).
Eligible participants will be healthcare professionals over 18 years of age who are in contact with patients with COVID-19, with negative IgG and IgM antibodies results for SARS-CoV-2 prior to their inclusion and sign the informed consent. After signing the informed consent, the participants will be randomized 1:1 to the intervention group (BCG vaccine) or control (placebo), a medical history will be performed, and a blood plasma sample will be obtained to determine specific antibodies against SARS-CoV-2.
The patients will be followed up for 6 months after the application of the vaccine, they will be contacted by phone every two weeks in order to identify the adverse effects of the vaccine (30 days after the application) as well as to identify symptoms of COVID-19, in addition, follow-up visits will be carried out at the third and sixth months, in each of these visits a blood plasma sample will be obtained and IgG and IgM antibodies will be measured.
Statistical Analysis Type: By intention to treatment
- Conditions
- BCG, COVID-19, SARS-CoV2, Corona Virus Infection
- Being tested
- BCG vaccine, Placebo
- Keywords
- Healthcare workers
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccineBiological
Also called Calmette-Guerin Bacillus vaccine
A single dose BCG vaccine intradermally (deltoid region of the right arm) 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis . (Tokio 172 strain)
PlaceboOther
A single dose intradermally ((deltoid region of the right arm) 0.1 ml of NaCl 0.9% solution
| Study group | Role | What they receive |
|---|---|---|
| BCG Vaccine | Experimental | A single dose BCG vaccine intradermally 0.1 ml. Receives: Biological: BCG vaccine |
| Placebo | Placebo comparator | A single dose intradermally 0.1 ml of NaCl 0.9% solution Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Demonstrate COVID- 19 disease incidence among Health care workers:
Cumulative incidence of infection in 6 months:
disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measured: During the 6 months study period
Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers:
Cumulative incidence of hospitalization for COVID-19
Measured: During the 6 months study period
Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers
Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months
Measured: During the 6 months study period
Hospitalization of severe disease COVID-19
Number of participants who needed hospitalization
Measured: During the 6 months study period
Oxygen supplementation in severe disease COVID-19
Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients
Measured: During the 6 months study period
Need for intubation or non-invasive ventilation for the patient.
Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients
Measured: During the 6 months study period
Critical care admission with SARS-CoV2
Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients
Measured: During the 6 months study period
Mortality associated to progressive pulmonary disease
Mortality associated to progressive pulmonary disease in hospitalized patients
Measured: During the 6 months study period
Secondary outcomes (9)
Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application.
Measured: 1 month after vaccine/placebo application
Calculate the incidence of COVID-19 complications
Measured: During the 6 months study period
Determine the mean days of hospitalization and days in intensive care unit by COIVD-19
Measured: During the 6 months study period
Calculate the cost associated with in-hospital medical care
Measured: During the 6 months study period
Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission:
SOFA score: PaO2/FIO2 (mm Hg), SaO2/FIO2, Platelets (×10³/µL), Bilirubin (mg/dL), Hypotension, Glasgow Coma Score and Creatinine (mg/dL) or urine output (mL/d).
Measured: During the 6 months study period
Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission:
APACHE: History of severe organ failure or immunocompromise Heart Failure Class IV, cirrhosis, chronic lung disease, or dialysis-dependent, Age, Temperature (C°), Mean arterial pressure (mmHg), pH, Sodium (mEq/L), Potassium (mEq/L), Creatinine (mg/dL), Hematocrit (%), WBC (x 109/L)
Measured: During the 6 months study period
Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission
CPR, ESR, Ferritin, D-dimer, LDH,Troponins, Procalcitonin, Interleukin-6, Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, MCV, HCM, MCHC, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Glucose, Urea, Creatinine, BUN, Sodium, Potassium, Chlorine, Calcium, Serum albumin, Direct bilirubin, Indirect bilirubin, Alkaline phosphatase, AST, ALT, bleeding time, Prothrombin Time, Activated partial thromboplastin time, Arterial / Venous Blood Gasometry, pH, pCO2, HCO3, pO2, SaO2%, Lactate.
Measured: During the 6 months study period
Registration of chronic medications
Measured: During the 6 months study period
Need for vasopressors
Measured: During the 6 months study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2020
- Study start21 Jul 2020
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BCGStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized double-blinded clinical trial, using computer software, participants will be allocated between two groups: Intervention: BCG vaccine intradermally 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis. (Tokio 172 strain). The application technique is based on the National Vaccination Manual version 2017. Comparator: Placebo, intradermally 0.1 ml of NaCl 0.9%
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 908 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario Dr. Jose E. Gonzalez
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, René Rodríguez-Gutiérrez, Hospital Universitario Dr. Jose E. Gonzalez
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04461379
- Sponsor's protocol ID
- EN20-00011
- Status last verified
- Nov 2020
- First submitted
- 2 Jul 2020
- Last updated
- 13 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention, Efficacy and Safety of BCG Vaccine in COVID-19- Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04461379
- Acronym / sponsor ID
- EN20-00011
- Conditions
- BCG, COVID-19, SARS-CoV2, Corona Virus Infection
- Keywords
- Healthcare workers
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 908 participants (estimated)
- Lead sponsor
- Hospital Universitario Dr. Jose E. GonzalezUniversity, hospital or other
- Study start
- 21 Jul 2020 (actual)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Jan 2021 (estimated)
- First posted
- 8 Jul 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.
In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.
Detailed description
The study design is a randomized, double-blinded, placebo-controlled clinical trial.
Age stratified randomization (<45 years and> 45 years) was performed using permuted blocks with allocation concealment.
The sample size is 908 patients. 454 patients in each stratum (227 with placebo and 227 with BCG vaccine).
Eligible participants will be healthcare professionals over 18 years of age who are in contact with patients with COVID-19, with negative IgG and IgM antibodies results for SARS-CoV-2 prior to their inclusion and sign the informed consent. After signing the informed consent, the participants will be randomized 1:1 to the intervention group (BCG vaccine) or control (placebo), a medical history will be performed, and a blood plasma sample will be obtained to determine specific antibodies against SARS-CoV-2.
The patients will be followed up for 6 months after the application of the vaccine, they will be contacted by phone every two weeks in order to identify the adverse effects of the vaccine (30 days after the application) as well as to identify symptoms of COVID-19, in addition, follow-up visits will be carried out at the third and sixth months, in each of these visits a blood plasma sample will be obtained and IgG and IgM antibodies will be measured.
Statistical Analysis Type: By intention to treatment
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized double-blinded clinical trial, using computer software, participants will be allocated between two groups: Intervention: BCG vaccine intradermally 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis. (Tokio 172 strain). The application technique is based on the National Vaccination Manual version 2017. Comparator: Placebo, intradermally 0.1 ml of NaCl 0.9%
| Arm | Type | Receives |
|---|---|---|
| BCG Vaccine | Experimental | Biological: BCG vaccineA single dose BCG vaccine intradermally 0.1 ml. |
| Placebo | Placebo comparator | Other: PlaceboA single dose intradermally 0.1 ml of NaCl 0.9% solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Health workers who are working onsite in patients' areas with COVID-19
- Age > 18 years
- Negative specific IgG and IgM antibodies test result for SARS CoV-2 before the enrollment.
- Provide a signed and dated informed consent form
Key exclusion criteria (17 listed)
- Age <18 years
- Positive test for specific antibodies IgG and IgM antibodies result for SARS Cov-2
- Primary or secondary immunosuppression
- Use of immunosuppression drugs, use of hydroxychloroquine, cloroquine, Azithromycin, Lopinavir/ritonavir, Ivermectin or any other drug used to treat patients COVID-19 before the enrollment.
- Chemotherapy treatment
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 |
|---|---|---|
| BCG vaccineAlso: Calmette-Guerin Bacillus vaccineA single dose BCG vaccine intradermally (deltoid region of the right arm) 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis . (Tokio 172 strain) | Biological | BCG Vaccine |
| PlaceboA single dose intradermally ((deltoid region of the right arm) 0.1 ml of NaCl 0.9% solution | Other | Placebo |
Primary outcome
Demonstrate COVID- 19 disease incidence among Health care workers:
Time frame: During the 6 months study period
Cumulative incidence of infection in 6 months: disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers:
Time frame: During the 6 months study period
Cumulative incidence of hospitalization for COVID-19
Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers
Time frame: During the 6 months study period
Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months
Hospitalization of severe disease COVID-19
Time frame: During the 6 months study period
Number of participants who needed hospitalization
Oxygen supplementation in severe disease COVID-19
Time frame: During the 6 months study period
Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients
Need for intubation or non-invasive ventilation for the patient.
Time frame: During the 6 months study period
Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients
Critical care admission with SARS-CoV2
Time frame: During the 6 months study period
Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients
Mortality associated to progressive pulmonary disease
Time frame: During the 6 months study period
Mortality associated to progressive pulmonary disease in hospitalized patients
9 secondary outcomes
Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application.
Time frame: 1 month after vaccine/placebo application
Calculate the incidence of COVID-19 complications
Time frame: During the 6 months study period
Determine the mean days of hospitalization and days in intensive care unit by COIVD-19
Time frame: During the 6 months study period
Calculate the cost associated with in-hospital medical care
Time frame: During the 6 months study period
Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission:
Time frame: During the 6 months study period
Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission:
Time frame: During the 6 months study period
Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission
Time frame: During the 6 months study period
Registration of chronic medications
Time frame: During the 6 months study period
Need for vasopressors
Time frame: During the 6 months study period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2020.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BCG vaccine in people with BCG and COVID-19, run by Hospital Universitario Dr. Jose E. Gonzalez at 1 site in Mexico.
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 4 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 13 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Demonstrate COVID- 19 disease incidence among Health care workers: (time frame: During the 6 months study period). The study lists 8 primary outcomes in all. 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 13 Nov 2020.