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

NCT04475302 | Completed Phase 3 DMC

• 1 other identifier: 2020010
• Study Type: interventional
• Target: 2,175
• Locations: 1 country
• Sites: 1

Brief 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. 1.To evaluate the effectiveness of BCG vaccination in terms of
2. 2.reducing the cumulative incidence of hospital admission and Intensive Care admission
3. 3.reducing the incidence of other respiratory febrile illness
4. 4.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.
5. 5.To measure biomarkers induced by BCG vaccination as correlates of risk/protection against SARS-Cov2 in a subset of individuals

Conditions

COVID

Outcome Measures

Primary Outcomes (1)

• Mortality due to COVID-19 disease

  Number of deaths due to COVID-19 disease

  6 months from study start date

Secondary Outcomes (1)

• Hospital admission and ICU admission due to Covid-19, Severity of Covid-19 (mild, moderate or severe), Hospital admission due to other respiratory febrile illness, immunological outcomes in the sub study

  10 months from study start date

Study Arms (2)

Intervention arm

EXPERIMENTAL

In the identified hotspots, BCG vaccine will be offered to all the elderly between 60 - 80 years of age. Those who get vaccinated will be followed for a period of 6-months.

Biological: BCG vaccine (Freeze-dried)

Control arm

NO INTERVENTION

1. in the hotspots, those who do not agree for vaccination, will be considered as controls. They will have an entry and exit interview at baseline and end of study period 2. in situations where we are unable to enrol the required number of controls from the vaccination hotspot zones, then hotspots in the neighbouring area / wards where BCG is not offered will be taken as control sites. Elderly between 60-80 years in those areas would be considered as control sites for the study. The elderly participants will be approached for an entry and exit interview, if they agree. If they do not agree for an exit interview at the end of 6-months, then the status of those in the control group would be collected either from the corporation records / other medical database.

Interventions

BCG vaccine (Freeze-dried) BIOLOGICAL

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.)

Intervention arm

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 60 years of age or older (\<100 years) with general good health, as confirmed by history and physical examination.
• No known history of HIV or on immunosuppressive drugs for malignancy or transplant
• Provide a signed and dated informed consent form

You may not qualify if:

• Positive for SARS-Cov2 infection
• Known HIV or other immune-suppressive treatments for malignancy or transplant
• Recently diagnosed as TB or currently on anti-TB treatment or anti-psychiatric medications
• Has any BCG vaccine contraindication
• H/o of previous administration of experimental MTB vaccines within the past 6 months.
• Sick and moribund individuals with Karnofsky score \<50
• Elderly individuals with or without co-morbid conditions like Diabetes mellitus, or Hypertension or Hyperlipidemia will be considered for this study, if they are on regular treatment.

Sponsors & Collaborators

• Tuberculosis Research Centre, India: lead
• ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu: collaborator
• All India Institute of Medical Sciences: collaborator
• National Institute for Research in Environmental Health, Bhopal, Madhya Pradesh: collaborator
• National Institute of Occupational Health, Ahmedabad, Gujarat: collaborator
• King Edward Memorial Hospital: collaborator
• National Institute for Implementation Research on Non-Communicable Disease: collaborator

Study Sites (1)

Tuberculosis Research Centre

Chennai, Tamil Nadu, 600031, India

Location

MeSH Terms

Interventions

BCG Vaccine; Freeze Drying

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Cryopreservation; Tissue Preservation; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Preservation, Biological; Therapeutics; Investigative Techniques

Study Officials

• Padmapriyadarsini Chandrasekaran, MBBS,DNB,MS

  National Institute for Research in Tuberculosis

  PRINCIPAL INVESTIGATOR

• Anant Mohan

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Randeep Guleria

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Tiwari R R.

  National Institute for Research in Environmental Health

  PRINCIPAL INVESTIGATOR

• Yogesh Sabde

  National Institute for Research in Environmental Health

  PRINCIPAL INVESTIGATOR

• Kamalesh Sarkar

  National Institute of Occupational Health

  PRINCIPAL INVESTIGATOR

• Asha Keetharam

  National Institute of Occupational Health

  PRINCIPAL INVESTIGATOR

• Hemant Deshmukh

  KEM Hospital

  PRINCIPAL INVESTIGATOR

• Rujuta Hadaye

  GSMC and KEM Hospital

  PRINCIPAL INVESTIGATOR

• Toteja G.S.

  National Institute for Implementation Research on Non-Communicable Disease

  PRINCIPAL INVESTIGATOR

• Subash Babu, MBBS, PhD

  NIH-International Center for Excellence in Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: In this study, as we are employing a control group that is not vaccinated against the disease to be prevented, but some clinical data are available to support the likely efficacy of the candidate vaccine, we will use unbalanced randomization and enrol participants to control group in the ratio of 2:1, so that majority of the study participant will receive the vaccine

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 17, 2020
• Study Start: July 1, 2020
• Primary Completion: September 20, 2021
• Study Completion: September 20, 2021
• Last Updated: July 8, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)