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BCG to Reduce Absenteeism Among Health Care Workers During the COVID-19 Pandemic

Phase 4
Completed
Conditions
Covid19
Morbidity
Absenteeism
Interventions
Biological: Saline
Biological: BCG-Denmark
Registration Number
NCT04641858
Lead Sponsor
University of Southern Denmark
Brief Summary

The COVID-19 pandemic challenges available hospital capacity. Strategies to protect health care workers (HCW) are desperately needed. Bacille Calmette- Guérin (BCG) has protective non-specific effects against other infections; a plausible immunological mechanism has been identified in terms of "trained innate immunity".

The primary objective of the study is to evaluate whether BCG can reduce unplanned absenteeism due to illness among HCW during the COVID-19 pandemic. Secondary objectives are to reduce the number of HCW that are infected with COVID-19, reduce hospital admissions for HCW and to improve the capacity for clinical research.

Design: Single-blind, parallel-group placebo-controlled multi-centre block randomized trial including a total of 1050 HCW. The study sites will be the Manhiça hospital in Mozambique, Central Hospital Dr. Agostinho Neto and Central Hospital Dr. Baptista de Sousa in Cape Verde and Hospital Nacional Simão Mendes and other hospitals in the capital Bissau in Guinea-Bissau. Population: HCW (nurses/physicians/others) ≥18 years.

Intervention: Block randomization 1:1 to intradermal standard dose (0.1 ml) of BCG vaccine or placebo (saline). Endpoints: Primary: Days of unplanned absenteeism due to illness. Secondary: Days of absenteeism because of documented COVID-19; cumulative incidence of infectious disease hospitalizations.

Follow-up: mobile phone interviews every second week, regarding symptoms, absenteeism and causes, COVID-19 testing (if done) and their results.

Perspectives: If BCG can reduce HCW absenteeism it has global implications. The intervention can quickly be scaled up all over the world.

Detailed Description

The main hypothesis for this study is that BCG vaccination of HCW reduces unplanned absenteeism due to illness by 20%.

Trial design Single-blind, parallel-group placebo-controlled adaptive multicentre trial, with block-randomisation 1:1 (treatment:placebo) in blocks of 20 within strata defined by gender (male/female) and occupational group (doctors/ nurses/other) to an intradermal standard 0.1 ml dose of BCG vaccine or placebo (saline) including a total of 1050 HCW (BCG arm and placebo arm).

Study population:

Health Care Workers defined as a person who delivers care and services to the sick and ailing either directly as doctors and nurses or indirectly as aides, helpers, laboratory technicians, or even medical waste handlers.

Intervention:

The intervention will consist of the administration of an intradermal injection of a standard 0.1 ml adult dose of attenuated Mycobacterium bovis BCG (Bacillus Calmette-Guerin), Danish strain 1331, 2-8 × 10\*5 CFU or the placebo comparator: intradermal standard 0.1 ml saline solution (NaCl 0.9%). Both BCG and saline solution will be injected in the skin over the upper deltoid muscle.

Blinding:

The BCG vaccine will be administered by study physicians/nurses, who are not blinded but also not involved in the data collection. Participants, data collectors and data entry clerks will be blinded to the treatment allocation.

In case of serious adverse events, the participant can be unblinded after consultation with the investigator or the vaccinating physician/nurse. When the study has ended, all participants will receive information about the intervention that they received.

Follow-up:

Follow-up will last for 6 months (182 days). Every second week, participants will be contacted over telephone and interviewed for symptoms and absenteeism from work. By the end of follow-up, participants will be invited for another POC test for COVID-19 serology.

Sample size:

The sample size was calculated on the basis of the primary hypothesis. A total of 1050 HCW randomized with an estimated loss to follow-up of 5%, and a mean number of days off work due to illness in the control group of 5 days (SD=5) over a 6-month period will demonstrate a reduction among BCG vaccinated of 20% for a mean absence of 4 days (80% power and alpha 0.05). The estimated loss to follow-up (5%) was based on past telephone-based surveys conducted in Mozambique and Bissau.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
668
Inclusion Criteria
  • health care worker (physician, nurse, or other) based at one of the research hospitals.
  • age ≥18 years
Exclusion Criteria
  • known allergy to (components of) BCG or serious adverse events to prior BCG administration;
  • known previous, active or latent infection with Mycobacterium tuberculosis or other mycobacterial species
  • fever (>38 C) within past 24 hours;
  • previous confirmed COVID-19 (positive test - PCR or antibody);
  • suspicion of active viral or bacterial infection
  • severely immunocompromised subjects
  • self-reported HIV infection
  • self-reported pregnancy;
  • active solid or non-solid malignancy or lymphoma within the prior two years;
  • contraindications for live attenuated vaccine administration.
  • not having a mobile phone.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlSalinePlacebo will be 0.1 ml sterile 0.9 % NaCl, which has a similar color and appearance as the resuspended BCG vaccine.
BCG-DenmarkBCG-DenmarkParticipants that are randomized in the active arm will receive an adult 0.1 ml dose of BCG vaccine (BCG-Denmark, AJ Vaccines) in the skin covering the right upper deltoid muscle. Each 0.1 ml vaccine contains between 200000 to 800000 colony forming units of the live attenuated strain of Mycobacterium bovis (BCG), Danish strain 1331.
Primary Outcome Measures
NameTimeMethod
Days of unplanned absenteeism due to illness6 months after inclusion

Unplanned absenteeism is defined by being absent from work due to causes other than holidays, parental leave, and other planned leaves, family assistance (including mourning leave) and quarantine measures.

Secondary Outcome Measures
NameTimeMethod
Death6 months after inclusion

Whether the participant died during follow-up

Days of unplanned absenteeism due to documented COVID-196 months after inclusion

Unplanned absenteeism is defined by being absent from work due to causes other than holidays, parental leave, and other planned leaves, family assistance (including mourning leave) and quarantine measures.

Cumulative incidence of hospital admissions due to illness (minus accidents).6 months after inclusion

Hospital admissions involves staying at a hospital for at least one night or more for medical reasons. It includes admissions to hospital wards and overnight stays in emergency departments.

Trial Locations

Locations (2)

Bandim Health Project

🇬🇼

Bissau, SAB, Guinea-Bissau

Manhiça Health Research Centre

🇲🇿

Manhiça, Maputo, Mozambique

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