BCG Vaccination for Healthcare Workers in COVID-19 Pandemic
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|ClinicalTrials.gov Identifier: NCT04379336|
Recruitment Status : Recruiting
First Posted : May 7, 2020
Last Update Posted : May 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 Sars-CoV2||Biological: Bacille Calmette-Guérin (BCG) Other: Placebo Comparator||Phase 3|
Morbidity and mortality attributable to COVID-19 is devastating global health systems and economies. Bacillus Calmette Guérin (BCG) vaccination has been in use for many decades to prevent severe forms of tuberculosis in children. Studies have also shown a combination of improved long-term innate or trained immunity (through epigenetic reprogramming of myeloid cells) and adaptive responses after BCG vaccination, which leads to non-specific protective effects in adults. Observational studies have shown that countries with routine BCG vaccination programs have significantly less reported cases and deaths of COVID-19, but such studies are prone to significant bias and need confirmation. To date, in the absence of direct evidence, WHO does not recommend BCG for the prevention of COVID-19.
This project aims to investigate in a timely manner whether and why BCG-revaccination can reduce infection rate and/or disease severity in health care workers during the SARS-CoV-2 outbreak in South Africa. These objectives will be achieved with a blinded, randomised controlled trial of BCG revaccination versus placebo in exposed front-line staff in hospitals in Cape Town. Observations will include the rate of infection with COVID-19 as well as the occurrence of mild, moderate or severe ambulatory respiratory tract infections, hospitalisation, need for oxygen, mechanical ventilation or death. HIV-positive individuals will be excluded. Safety of the vaccines will be monitored. A secondary endpoint is the occurrence of latent or active tuberculosis. Initial sample size and follow-up duration is at least 500 workers and 52 weeks. Statistical analysis will be model-based and ongoing in real time with frequent interim analyses and optional increases of both sample size or observation time, based on the unforeseeable trajectory of the South African COVID-19 epidemic, available funds and recommendations of an independent data and safety monitoring board.
Given the immediate threat of the SARS-CoV-2 epidemic the trial has been designed as a pragmatic study with highly feasible endpoints that can be continuously measured. This allows for the most rapid identification of a beneficial outcome that would lead to immediate dissemination of the results, vaccination of the control group and outreach to the health authorities to consider BCG vaccination for all qualifying health care workers.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Efficacy will be determined based on documented SARS-CoV-2 infection and incidence of hospitalization. The analysis will be an intention-to-treat analysis with estimation of hazard ratio between the two arms using a Cox proportional hazard model. Adverse events will be summarized using descriptive statistics per study arm. The analysis will be a model-based analysis of cumulative data on general health status as a function of risk factors, treatment arm and time.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double Blinded|
|Official Title:||Reducing Morbidity and Mortality in Health Care Workers Exposed to SARS-CoV-2 by Enhancing Non-specific Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial|
|Actual Study Start Date :||May 4, 2020|
|Estimated Primary Completion Date :||April 28, 2021|
|Estimated Study Completion Date :||April 28, 2021|
Experimental: Bacille Calmette-Guérin (BCG)
Participants will receive an intradermal injection of 0.1ml of the suspended BCG vaccine which accounts for 0.075mg of attenuated Mycobacterium bovis. BCG-Vaccin SSI [Statens Serum Institut], Danish strain 1331.
Biological: Bacille Calmette-Guérin (BCG)
BCG vaccine will be given intradermally in the upper arm after randomization.
Other Name: BCG-Vaccin SSI [Statens Serum Institut], Danish strain 1331
Placebo Comparator: Placebo
The placebo used for this study is 0.9% Sodium Chloride (NaCl). Participants that are randomized to the control arm will receive a placebo injection of 0.1ml 0.9% NaCl, which is the same volume and has the same colour as the suspended BCG vaccine.
Other: Placebo Comparator
Placebo injection will be given intradermally in the upper arm after randomization.
Other Name: 0.9% Sodium Chloride
- Incidence of HCWs hospitalized due to COVID-19 per arm [ Time Frame: 52 weeks ]To compare the incidence of HCWs hospitalized due to COVID-19 per arm.
- Incidence of SARS-CoV-2 infection per arm [ Time Frame: 52 weeks ]To determine the incidence of SARS-CoV-2 infection in HCW by molecular or serological testing (as available) at entry, 10, 26 and/or 52 weeks.
- Incidence of upper respiratory tract infections per arm [ Time Frame: 52 weeks ]To compare the incidence of symptoms of upper respiratory tract infection per arm.
- Days of unplanned absenteeism due to COVID-19 or any reason per arm [ Time Frame: 52 weeks ]To compare the number of days of (unplanned) absenteeism because of documented SARS-CoV-2 infection, COVID-19 or any reason per arm.
- Incidence of hospitalization for any reason per arm [ Time Frame: 52 weeks ]To compare the incidence of hospitalization of HCW for any reason per arm.
- Incidence of intensive care unit admission per arm [ Time Frame: 52 weeks ]To compare the incidence of intensive care admission of HCW due to COVID-19 or any reason per arm.
- Incidence of death per arm [ Time Frame: 52 weeks ]To compare the incidence of death of HCW due to COVID-19 or any reason per arm.
- Prevalence of latent TB infection [ Time Frame: 52 weeks ]To describe the prevalence of latent TB infection as determined by interferon gamma release assay (IGRA) at enrolment and at week 52.
- Incidence of active TB per arm [ Time Frame: 52 weeks ]To compare the incidence of active TB of HCW per arm.
- Compare the effect of latent TB on morbidity and mortality due to COVID-19 per arm [ Time Frame: 52 weeks ]To compare the effect of latent TB infection on morbidity and mortality of HCW due to COVID-19 per arm. The risk of morbidity and mortality of latent TB infected individuals is not known, we will examine whether there is a higher risk of disease severity and poor outcomes in this group.
- Incidence of treatment related adverse events [ Time Frame: 52 weeks ]To compare the incidence of grade 2 or higher adverse events and vaccination site reactions per arm.
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): NCT04379336
|Contact: Caryn M Upton, MBChB||+27 21 510 firstname.lastname@example.org|
|Contact: Christelle Van Niekerk||+27 21 100 email@example.com|