Reducing Health Care Workers Absenteeism in Covid-19 Pandemic Through BCG Vaccine

NCT04328441 | Completed Phase 3

• 1 other identifier: NL73249.041.20
• Study Type: interventional
• Target: 1,511
• Locations: 1 country
• Sites: 9

Brief Summary

Rationale: Covid-19 spreads rapidly throughout the world. A large epidemic in the Netherlands would seriously challenge the available hospital capacity, and this would be augmented by absenteeism of healthcare workers (HCW). Strategies to prevent absenteeism of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported significant reductions in morbidity and mortality. The hypothesis is that BCG vaccination can reduce HCW absenteeism during the epidemic phase of Covid-19. Objective: Primary objective: To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of Covid-19. Secondary objective: To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of Covid-19. Study design: A placebo-controlled adaptive multi-centre randomized controlled trial. Study population: HCW with direct patient contacts among which nurses and physicians working at emergency rooms and wards where Covid-19-infected patients are treated. Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio. Main study parameters/endpoints: Primary endpoint: number of days of (unplanned) absenteeism for any reason. Secondary endpoints include the number of days of (unplanned) absenteeism because of documented Covid-19 infection, and the cumulative incidence of hospital admission, Intensive Care Admission, and death. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of Covid-19 infection. The primary endpoint and the adaptive design with frequent interim analyses facilitate maximum efficiency of the trial, so that results can inform policy making during the ongoing epidemic.

Conditions

COVID-19

Keywords

Health care workers

Outcome Measures

Primary Outcomes (1)

• Health Care Workers absenteeism

  Number of days of unplanned absenteeism for any reason

  Maximum of 365 days

Secondary Outcomes (18)

• the cumulative incidence of documented COVID-19

  Maximum of 365 days

• the cumulative incidence of Hospital Admission due to documented COVID-19

  Maximum of 365 days

• the number of days of unplanned absenteeism, because of documented COVID-19

  Maximum of 365 days

• the cumulative incidence of self-reported acute respiratory symptoms or fever

  Maximum of 365 days

• the cumulative incidence of death due to documented COVID-19

  Maximum of 365 days

Study Arms (2)

BCG vaccine

EXPERIMENTAL

Intracutaneously 0.1ml BCG vaccine, which accounts for 0.075mg of attenuated Mycobacterium bovis.

Drug: BCG Vaccine

Placebo

PLACEBO COMPARATOR

Intracutaneously 0.1ml of 0.9% NaCl solution

Drug: Placebo

Interventions

BCG Vaccine DRUG

Intracutaneously 0.1ml BCG vaccine, which accounts for 0.075mg of attenuated Mycobacterium bovis

Also known as: Danish strain 1331

BCG vaccine

Placebo DRUG

Intracutaneously 0.1ml NaCl 0,9%

Also known as: NaCl 0,9%

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (≥18 years)
• Male or female
• Hospital personnel (expected to) taking care for patients with SARS CoV-2 infection

You may not qualify if:

• Known allergy to (components of) the BCG vaccine or serious adverse events to prior BCG administration
• Known active or latent Mycobacterium tuberculosis or with another mycobacterial species. A history with- or a suspicion of M. tuberculosis infection.
• Fever (\>38 C) within the past 24 hours
• Pregnancy
• Suspicion of active viral or bacterial infection
• Vaccination in the past 4 weeks or expected vaccination during the study period, independent of the type of vaccination.
• Active solid or non-solid malignancy or lymphoma within the prior two years
• Direct involvement in the design or the execution of the BCG-CORONA study
• Expected absence from work of ≥4 of the following 12 weeks due to any reason (holidays, maternity leave, retirement, planned surgery etc)
• Employed to the hospital \< 22 hours per week
• Not in possession of a smartphone

Sponsors & Collaborators

• UMC Utrecht: lead
• Radboud University Medical Center: collaborator

Study Sites (9)

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, Netherlands

Location

Radboud UMC

Nijmegen, Gelderland, Netherlands

Location

Sint Maartenskliniek

Nijmegen, Gelderland, Netherlands

Location

Jeroen Bosch ziekenhuis

's-Hertogenbosch, North Brabant, Netherlands

Location

Noordwest Ziekenhuisgroep locatie Alkmaar

Alkmaar, North Holland, Netherlands

Location

Leiden University Medical Center

Leiden, South Holland, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Location

Hagaziekenhuis

The Hague, South Holland, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Related Publications (1)

• Ten Doesschate T, Moorlag SJCFM, van der Vaart TW, Taks E, Debisarun P, Ten Oever J, Bleeker-Rovers CP, Verhagen PB, Lalmohamed A, Ter Heine R, van Crevel R, van de Wijgert J, Janssen AB, Bonten MJ, van Werkhoven CH, Netea MG; BCG-CORONA study team#. Two Randomized Controlled Trials of Bacillus Calmette-Guerin Vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: A structured summary of the study protocols for two randomised controlled trials. Trials. 2020 Jun 5;21(1):481. doi: 10.1186/s13063-020-04389-w.

  PMID: 32503602 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Marc Bonten, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Unblinded are the pharmacist and the research nurse that administers the study medication. These persons are not involved in the further conduction of the trial or in the assessment of outcomes.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. M.J.M. Bonten

Study Record Dates

• First Submitted: March 27, 2020
• First Posted: March 31, 2020
• Study Start: March 25, 2020
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: June 3, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The content of the study protocol is published. The statistical analysis plan is attached. The informed consent form (in Dutch) could be obtained by sending a mail to one of the contact persons. The clinical study report and analytic code could be obtained by sending a mail to one of the contact persons after publication of the study in a peer-reviewed journal.

Locations

NL (9)