BCG Vaccine in Reducing Morbidity and Mortality in Elderly Individuals in COVID-19 Hotspots

Summary

Rationale: SARS-CoV2 viral infection is spreading rapidly throughout the world and in India the epidemic poses a major threat to the public health system. Elderly individuals, especially those with diabetes, hypertension, other chronic diseases are at high risk of mortality. Strategies to protect these individuals are 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. Based on the capacity of BCG to reduce the incidence of respiratory tract infections in children and adults, to exert antiviral effects in experimental models; and to reduce viremia in an experimental human model of viral infection, the hypothesis is that BCG vaccination will partially protect against mortality in high-risk, elderly individuals.

Primary Objective: To evaluate the effectiveness of BCG vaccination in preventing morbidity and mortality due to COVID-19 in elderly individuals aged between 60 to 80 years living in COVID-19 hotspots in India.

Secondary objectives:

1. To evaluate the effectiveness of BCG vaccination in terms of

1. reducing the cumulative incidence of hospital admission and Intensive Care admission
2. reducing the incidence of other respiratory febrile illness
2. To determine the innate and adaptive immune responses, IgM, IgG and IgA antibody titers generated by BCG vaccination (both total and SARS-Cov2 specific) in a subset of individuals.
3. To measure biomarkers induced by BCG vaccination as correlates of risk/protection against SARS-Cov2 in a subset of individuals

Method and Analysis:

Study design: Intervention study Study population: Elderly 60 - 80 years of age residing in designated hotspots for SARS-Cov2 infection Study Intervention: One dose of 0.1ml BCG vaccine, given intradermally. Elderly individuals not vaccinated from the same hotspot area or from neighbouring hotspot wards areas will be considered as the controls. Study sites: Chennai, Mumbai, Ahmedabad, Bhopal, Jodhpur and New Delhi. Study Sample size: 1450 individuals between 60-80 years of age will receive BCG vaccination while 725 individuals will be controls without vaccination Study duration: 6 months/participant. Enrolment at each site will be over: 4 months. Each participant will be followed for 6 months post vaccination. Primary Outcome Measures: During the study period (6-months), Proportion of individuals receiving the BCG vaccination who are asymptomatic but become PCR-positive or seroconvert during the 6-month of study period. Proportion of patients with development of COVID-19 disease (either PCR-positive or seroconvert with symptoms) during the study period. Proportion of patients with Severe COVID-19 disease and death due to Covid-19 disease

Conditions

• COVID

Interventions

BIOLOGICAL

BCG vaccine (Freeze-dried)

single dose of BCG vaccine (Freeze-dried) manufactured by Serum Institute of India, Pune. The composition of BCG vaccine is Live, attenuated BCG (Bacillus Calmette-Guerin Strain). (Each 1 ml contains between 2 x 106 and 8 x 106 Colony Forming Units (C.F.U.) with Diluent: Sodium Chloride Injection I.P.)

Sponsors & Collaborators

• ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu

  collaborator UNKNOWN

• All India Institute of Medical Sciences

  collaborator OTHER

• National Institute for Research in Environmental Health, Bhopal, Madhya Pradesh

  collaborator UNKNOWN

• National Institute of Occupational Health, Ahmedabad, Gujarat

  collaborator UNKNOWN

• King Edward Memorial Hospital

  collaborator OTHER

• National Institute for Implementation Research on Non-Communicable Disease

  collaborator UNKNOWN

• Tuberculosis Research Centre, India

  lead OTHER_GOV

Principal Investigators

• Padmapriyadarsini Chandrasekaran, MBBS,DNB,MS · National Institute for Research in Tuberculosis

• Anant Mohan · All India Institute of Medical Sciences

• Randeep Guleria · All India Institute of Medical Sciences

• Tiwari R R. · National Institute for Research in Environmental Health

• Yogesh Sabde · National Institute for Research in Environmental Health

• Kamalesh Sarkar · National Institute of Occupational Health

• Asha Keetharam · National Institute of Occupational Health

• Hemant Deshmukh · KEM Hospital

• Rujuta Hadaye · GSMC and KEM Hospital

• Toteja G.S. · National Institute for Implementation Research on Non-Communicable Disease

• Subash Babu, MBBS, PhD · NIH-International Center for Excellence in Research

Study Design

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

60 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-07-01

Primary Completion

2021-09-20

Completion

2021-09-20

Countries

• India

Study Locations