NCT04384549: COVID-BCG

Efficacy of BCG Vaccination in the Prevention of COVID19 Via the Strengthening of Innate Immunity in Health Care Workers

Status unknown Phase 3 Last updated 18 August 2020

What this trial tests

Phase 3 trial testing BCG GROUP in Infection in 1,120 participants. Status unknown.

Timeline

20 May 2020

Primary endpoint
20 February 2021

20 February 2021

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	prevention
Enrollment	1,120
Start date	20 May 2020
Primary completion	20 February 2021
Estimated completion	20 February 2021
Sites	1 location across France

Drugs / interventions tested

• BCG GROUP
• PLACEBO GROUP

Conditions studied

• Infection — all drugs for Infection →
• Viral, Agent as Cause of Disease Classified Elsewhere — all drugs for Viral, Agent as Cause of Disease Classified Elsewhere →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Infection or Viral, Agent as Cause of Disease Classified Elsewhere. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Healthcare Workers (HCW) are at high risk for COVID-19. In addition to the risk of serious forms among HCW, significant absenteeism due to illness would have dramatic consequences in our ability to fight COVID-19. No coronavirus vaccine is available today and drug treatments are only at the start of clinical evaluation. Available since 1921, the bacillus Calmette and Guérin (BCG) is the most widely used vaccine in the world (\> 3 billion doses administered) with an extremely low rate of adverse effects. BCG is indicated for the prevention of tuberculosis (TB), but more recent studies have shown that it also has nonspecific immune properties which may be interesting in the current COVID-19 epidemic. Data in mice and in humans have demonstrated protection conferred by BCG against viral respiratory infections such as influenza. In countries with high endemic TB, BCG decreases the incidence of acute respiratory infections by up to 80%, neonatal BCG vaccination has been shown to greatly reduce the risk of sepsis and of hospitalization of children for reasons other than TB. A recent study conducted in South Africa showed that re-vaccination with BCG in adults reduced the incidence of respiratory infections by 70% compared to unvaccinated controls. Beyond respiratory infections, BCG has also shown protective effects against inflammatory diseases. These non-specific beneficial effects are likely linked to the induction of "trained innate immunity", implying epigenetic and metabolic re-programming of innate immune cells. It is therefore possible that revaccination with BCG could significantly reduce the incidence and severity of COVID-19. Very recent ecological observations indeed suggest an inverse correlation between BCG vaccination coverage and the morbidity and mortality of COVID-19. In this context several trials began in Europe and Australia to evaluate the efficacy of BCG vaccination in populations at risk of exposure (HCW) or severe disease (elderly). This study is aligned with studies carried out in Australia, The Netherlands and Spain. In contrast to these latter studies, virtually all French study participants have been vaccinated in their childhood, since BCG vaccination was mandatory in France in neonates until 2007, and in HCW until recently. Therefore, the French study will be in a unique situation to evaluate the effect of re-vaccination with BCG in the context of BCG priming decades before revaccination.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Coronavirus vaccine development: from SARS and MERS to COVID-19.
   Li YD, Chi WY, Su JH, Ferrall L, et al · · 2020 · cited 242× · PMID 33341119 · DOI 10.1186/s12929-020-00695-2
2. 100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19.
   Lobo N, Brooks NA, Zlotta AR, Cirillo JD, et al · · 2021 · cited 114× · PMID 34131332 · DOI 10.1038/s41585-021-00481-1
3. Advances in Infectious Disease Vaccine Adjuvants.
   Fan J, Jin S, Gilmartin L, Toth I, et al · · 2022 · cited 68× · PMID 35891284 · DOI 10.3390/vaccines10071120
4. Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines.
   Flanagan KL, Best E, Crawford NW, Giles M, et al · · 2020 · cited 64× · PMID 33123165 · DOI 10.3389/fimmu.2020.579250
5. Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses.
   Hensel J, McAndrews KM, McGrail DJ, Dowlatshahi DP, et al · · 2020 · cited 57× · PMID 33110184 · DOI 10.1038/s41598-020-75491-x
6. The BCG Vaccine for COVID-19: First Verdict and Future Directions.
   Gonzalez-Perez M, Sanchez-Tarjuelo R, Shor B, Nistal-Villan E, et al · · 2021 · cited 50× · PMID 33763077 · DOI 10.3389/fimmu.2021.632478
7. The 2020 Pandemic: Current SARS-CoV-2 Vaccine Development.
   Alturki SO, Alturki SO, Connors J, Cusimano G, et al · · 2020 · cited 49× · PMID 32973779 · DOI 10.3389/fimmu.2020.01880
8. Outbreak of COVID-19: An emerging global pandemic threat.
   Peng M. · · 2020 · cited 42× · PMID 32768974 · DOI 10.1016/j.biopha.2020.110499