NCT04414267

Brief Summary

Based on findings of the interim analysis of the ACTIVATE study showing 53% decrease of the incidence of all new infections with BCG vaccination, a new trial is designed aiming to validate if BCG can protect against COVID-19 (Corona Virus Disease-19).The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of participants susceptible to COVID-19 with BCG vaccine may modulate their disease susceptibility for COVID-19. This will be validated using both clinical and immunological criteria. At the same time, a sub-study will be conducted and the mechanism of benefit from BCG vaccination by assessing its effect on vascular endothelial function and mononuclear blood cells will be studied

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
301

participants targeted

Target at P50-P75 for phase_4 covid19

Timeline
Completed

Started May 2020

Typical duration for phase_4 covid19

Geographic Reach
1 country

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 26, 2020

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

June 1, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 4, 2020

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 28, 2021

Completed
9 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 7, 2021

Completed
Last Updated

May 11, 2021

Status Verified

May 1, 2021

Enrollment Period

11 months

First QC Date

June 1, 2020

Last Update Submit

May 9, 2021

Conditions

Keywords

COVID-19SARS-CoV-2VaccinationBacillus Calmette-Guérin vaccination

Outcome Measures

Primary Outcomes (1)

  • Positive for the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 3.

    This is set on visit 3 (90 ± 5 days from the date of visit 1). The two groups of vaccination are compared for the primary endpoints which is composite. Patients who meet any of the following will be considered to meet the primary endpoint: * Positive for the respiratory questionnaire endpoint when at least one of the following combination is met either at visit 2 and/or at visit 3: * One situation definitively related to COVID-19 * All four questions of symptoms possibly related to COVID-19 * At least two questions of symptoms possibly related to COVID-19 as well as need for admission at the emergency department of any hospital and/or need for intake of antibiotics * At least four questions of symptoms probably related to COVID-19 one of which is "need for admission at the emergency department of any hospital and/or need for intake of antibiotics" * Positive IgG or IgM antibodies against SARS-CoV-2

    Visit 3 (90 +/- 5 days)

Secondary Outcomes (15)

  • Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 4

    Visit 4 (135 +/- 5 days)

  • Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 5

    Visit 5 (180 +/- 5 days)

  • Prevalence of IgG/IgM against SARS-CoV-2

    Screening Visit and Visit 3 (90 +/- 5 days)

  • Analysis of each of the components of the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19.

    Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

  • The impact of new cardiovascular events between the two study groups

    Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

  • +10 more secondary outcomes

Study Arms (2)

BCG vaccine

EXPERIMENTAL

One intradermal injection of 0.1ml of BCG (BCG vaccine Moscow strain 361-1; Serum Institute of India Pvt. Ltd)

Biological: BCG vaccine

Placebo

PLACEBO COMPARATOR

One intradermal injection of 0.1ml of sodium chloride 0.9%

Biological: Placebo

Interventions

BCG vaccineBIOLOGICAL

Patients susceptible to SARS-CoV-2 infection will be vaccinated with one intradermal injection of 0.1ml of BCG vaccine

Also known as: BCG Vaccine (Freeze Dried)
BCG vaccine
PlaceboBIOLOGICAL

Patients susceptible to SARS-CoV-2 infection will be vaccinated with one intradermal injection of 0.1ml of sodium chloride 0.9%

Also known as: Saline
Placebo

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent
  • Male or female
  • Age more than or equal to 50 years based on the precise date of birth. Female participants are allowed on the premise that they are post-menopausal.
  • History of at least one of the following:
  • coronary heart disease;
  • chronic obstructive pulmonary disease;
  • Charlson's comorbidity index (CCI) more than 3
  • Negative serum testing for immunoglobulin G and M against SARS-CoV-2
  • Skin tuberculin test diameter less than 10mm

You may not qualify if:

  • Deny to written informed consent
  • Age less than 50 years
  • Known infection by the Human Immunodeficiency Virus-1 (HIV-1)
  • History of congenital immunodeficiency
  • History of solid organ transplantation
  • History of bone marrow transplantation
  • Intake of chemotherapy the last two months
  • Intake of radiotherapy the last two months
  • Active hematological or solid tumor malignancy
  • History of any anti-cytokine therapies
  • History of oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than the last 3 months

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

General Hospital of Argolida - Nafplion Unit

Nafplion, Argos, 21100, Greece

Location

2nd Department of Internal Medicine, University General Hospital of Alexandroupolis

Alexandroupoli, 68100, Greece

Location

Department of Therapeutics, Alexandra General Hospital

Athens, 115 28, Greece

Location

1st Department of Internal Medicine, General Hospital of Athens G. GENNIMATAS

Athens, 11527, Greece

Location

2nd University Department of Internal Medicine, IPPOKRATEION General Hospital of Athens

Athens, 11527, Greece

Location

3rd University Department of Internal Medicine, General Hospital of Chest Diseases of Athens I SOTIRIA

Athens, 11527, Greece

Location

4th Department of Internal Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School

Athens, 12462, Greece

Location

Department of Pulmonary Medicine- General Hospital of Kerkyra

Corfu, 49100, Greece

Location

General Hospital of Korinthos

Corinth, 20100, Greece

Location

1st Department of Internal Medicine, General University Hospital of Ioannina

Ioannina, 45500, Greece

Location

Department of Internal Medicine, General Hospital of Karditsa

Karditsa, 43100, Greece

Location

Department of Internal Medicine, Patras University Hospital

Pátrai, Greece

Location

General Hospital of Ptolemaida MPODOSAKEIO

Ptolemaida, 50200, Greece

Location

1st Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki

Thessaloniki, 54621, Greece

Location

General Hospital of Imathia - Veria Unit

Véria, 59100, Greece

Location

MeSH Terms

Conditions

COVID-19Virus DiseasesCoronavirus InfectionsCoronary DiseasePulmonary Disease, Chronic Obstructive

Interventions

BCG VaccineFreeze DryingSodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesMyocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesLung Diseases, ObstructiveChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tuberculosis VaccinesBacterial VaccinesVaccinesBiological ProductsComplex MixturesCryopreservationTissue PreservationHistocytological Preparation TechniquesCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesPreservation, BiologicalTherapeuticsInvestigative TechniquesChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Antonios Papadopoulos, MD, PhD

    National Kapodistrian University of Athens, Medical School

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Patients vaccinated with placebo or BCG
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 1, 2020

First Posted

June 4, 2020

Study Start

May 26, 2020

Primary Completion

April 28, 2021

Study Completion

May 7, 2021

Last Updated

May 11, 2021

Record last verified: 2021-05

Data Sharing

IPD Sharing
Will not share

Locations