Prevention Of Respiratory Tract Infection And Covid-19 Through BCG Vaccination In Vulnerable Older Adults
Status:
Recruiting
Trial end date:
2021-07-25
Target enrollment:
Participant gender:
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. 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.