Table 1.
Characteristics of Clinical Trials
| Clinical Trial | Start and End Dates | Phase | Samples | Follow-Up | Inclusion Criteria | Main Outcome | Status | Results | Respiratory Complications | Funder | Country | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RBR-4kjqtg | 20.08.2020–31.08.2021 | II | 68 controls (no placebo) vs 70 BCG Moscow | 180 days via telemedicine | Healthcare workers (HCWs) exposed to SARS-CoV-2; male or female; 18 years or older; positive history of previous BCG vaccination and negative history of COVID-19 | Incidence of SARS-CoV-2 infection | Finalized | Groups were not significantly different in their possibility of acquiring the infection. Adverse events: only mild local lesion | Possibly no worsening of respiratory complications by BCG. Protection could not be proven | CNPq/MCTI | Brazil | [23] |
| NCT04373291 | 18.05.2020–01.10.2021 | III | 1293 | 180 days | Hospital personnel in participating hospital for more than 22 hours per week; male or female; 18 years or older | Absenteeism from work | Recruitment completed | No study results reported | Not measured directly – hospital admissions as secondary outcome indirect measures | Bandim Health Project | Denmark | [24] |
| NCT04327206 | 30.03.2020–27.05.2022 | III | 6828 controls vs BCG Danish | Every 3 months until 12 months, in person | HCWs; male or female; 18 years or older | Incidence of symptomatic or severe COVID- 19 at 6 months | Finalized | Only serology results available: BCG vaccination reduced cytokines associated with severe disease | Incidence and severity of febrile respiratory illness – no results available | Murdoch Childrens Research Institute | Australia, Netherlands, Spain, UK, and Brazil | [25,26] The BRACE trial |
|
NCT04328441 NCT03987919 |
24.03.2020–31.03.2021 | III | 758 placebo vs 753 BCG Danish | 12 months by weekly questionnaire via app | HCWs with exposure to SARS-CoV-2; 18 years or older; male or female | Reduce HCW absenteeism due to illness during the COVID-19 pandemic | Finalized | No significant difference in absenteeism due to any cause or incidence of documented SARS-CoV-2. Adverse events: only mild | No difference in incidence of respiratory symptoms | UMC Utrecht | Netherlands | [27] |
| NCT0441733 | 16.04.2020–01.05.2021 | IV | 1006 placebo vs 1008 BCG Danish or Denmark | 12 months by weekly or monthly questionnaire via app or phone | Male or female; elderly ≥60 years | Cumulative incidence of respiratory tract infection (RTI) requiring medical intervention | Finalized | No significant difference in incidence of RTI or documented SARS-CoV-2 infection. Adverse events: only mild | No difference in incidence of RTI or dyspnea | Radboud University Medical Center | Netherlands | [28] |
| NCT04414267 | 26.05.2020–19.04.2021 | III | 153 placebo vs 148 BCG Moscow or India | 6 months | Male or female; age ≥50 years plus history of at least one of the following: coronary heart disease; chronic obstructive pulmonary disease; Charlson’s comorbidity index (CCI) >3. Negative serum testing for immunoglobulin G and M against SARS-CoV-2; skin tuberculin test diameter less than 10 mm | Incidence of COVID-19 and presence of anti-SARS-CoV-2 antibody | Finalized | BCG revaccination resulted in 68% relative risk reduction of infection at 6 months. No difference in infection incidence at 3 months. Adverse event: only mild local lesion | Respiratory symptoms and their severity were asked about in questionnaires. No significant difference between groups | Hellenic Institute for the Study of Sepsis | Greece | [29] The ACTIVATE-2 trial |
| Clinical Trials Registry – India (CTRI number CTRI/2020/07/026668) | 10.2020–12.2021 | III | 249 placebo vs 246 BCG India | 1, 3, 6, and 9 months | Male or female with underlying conditions (poorly controlled diabetes, chronic kidney or lung disease, etc); 18–60 years old | Risk of SARS-CoV-2 infection | Finalized | BCG arm had 8.4% reduction in the incidence of probable infection | BCG arm had significantly lower incidence of severe COVID-19, oxygen requirement, and hospitalization (p=0.03) | Three hospitals in different areas of India | India | [30] The BRIC trial |
| NCT04632537 | 07.12.2020–23.03.2021 | III | – | 6 months | HCWs exposed to SARS-CoV-2; male or female; 18–64 years old | Risk of SARS-CoV-2 infection and disease severity | Withdrawn (funding issues) | – | Oxygen/intensive care/mechanical ventilation requirement; incidence of self-reported respiratory symptoms – no results available | Henry M. Jackson Foundation for the Advancement of Military Medicine | United States | – |
| NCT04348370 | 20.04.2020–05.2022 | IV | 1800 | 6 months | HCWs directly exposed to SARS-CoV-2; male or female; 18–75 years old | Risk of SARS-CoV-2 infection and disease severity | Active, not recruiting | No study results reported | Oxygen/intensive care/mechanical ventilation requirement – no results available | Texas A&M University | United States | The BADAS trial |
| NCT04362124 | 08.2020–11.2021 | III | – | 360 days | HCWs directly exposed to SARS-CoV-2; male or female; 18–65 years old; negative COVID-19 test and asymptomatic | Incidence of SARS-CoV-2 infection | Withdrawn (funding issues) | – | Severe COVID-9 – no results available | Universidad de Antioquia | Colombia | – |
| NCT04659941 | 01.10.2020–01.10.2022 | II | 752 | 6 months | HCWs never infected with SARS-CoV-2; male or female; 18 years or older | Incidence of SARS-CoV-2 infection | Active, not recruiting | No study results reported | Severe disease – no results available | Universidade Federal do Rio de Janeiro | Brazil | – |
| NCT04369794 | 01.10.2020–30.08.2023 | III | 186 placebo vs 175 BCG Brazil or India | Weekly for 4–6 weeks, in person | Infected with SARS-CoV-2 within the past 14 days; male or female; 18 years or older | Safety of BCG revaccination in COVID-19 convalescent patients | Active, not recruiting | Adverse events: mostly mild local lesions. Possibility of increased dyspnea in the second week post-BCG | Higher proportion of dyspnea in the BCG recipients in the second week, which may have been due to failed randomization | University of Campinas | Brazil | [10,31] The BATTLE trial |
| NCT04461379 | 21.07.2020–01.01.2021 | III | 908 | 6 months | HCWs directly exposed to SARS-CoV-2; male or female; 18 years or older; | Incidence of SARS-CoV-2 infection | Active, not recruiting | No study results reported | Oxygen/intensive care/mechanical ventilation requirement; mortality associated with respiratory disease – no results available | Hospital Universitario Dr. Jose E. Gonzalez | Mexico | – |
| NCT04350931 | 20.04.2020–01.12.2020 | III | 900 | Daily | HCWs exposed to SARS-CoV-2; male or female; 18 years or older | Incidence of SARS-CoV-2 infection | Unknown | No study results reported | Symptom of dyspnea | Ain Shams University | Egypt | – |