CTRI Number	CTRI/2020/06/025854 [Registered on: 13/06/2020] Trial Registered Prospectively
Last Modified On:	15/09/2021
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Vaccine
Study Design	Non-randomized, Active Controlled Trial
Public Title of Study Modification(s)	BCG vaccination against COVID-19
Scientific Title of Study	Study to Evaluate the Effectiveness of BCG vaccine in Reducing Morbidity and Mortality in Elderly individuals in COVID-19 Hotspots in India
Secondary IDs if Any Modification(s)	Secondary ID  Registry  Version 3.2, 17/05/2020  Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  C Padmapriyadarsini  Address  Department of Clinical Research ICMR-National Institute for Research in Tuberculosis No.1, Satyamoorthy Road Chetput, Chennai Chennai TAMIL NADU 600031 India  Phone  9498022949   Fax  044-28362528   Email  pcorchids@gmail.com
Details Contact Person Scientific Query Modification(s)	Name  C Padmapriyadarsini  Address  Department of Clinical Research ICMR-National Institute for Research in Tuberculosis, No.1, Satyamoorthy Road Chetput, Chennai Chennai TAMIL NADU 600031 India  Phone  9498022949   Fax  044-28362528   Email  pcorchids@gmail.com
Details Contact Person Public Query Modification(s)	Name  Srikanth Tripathy  Address  ICMR-National Institute for Research in Tuberculosis No.1, Satyamoorthy Road Chetput, Chennai Chennai TAMIL NADU 600031 India  Phone  28369500   Fax  044-28362528   Email  srikanthtripathy@gmail.com
Source of Monetary or Material Support Modification(s)	Indian Council of Medical Research V. Ramalingaswami Bhawan, P.O. Box No. 4911 Ansari Nagar, New Delhi - 110029, India
Primary Sponsor	Name  Indian Council of Medical Research  Address  V. Ramalingaswami Bhawan, Ansari Nagar, New Delhi, Delhi 110029  Type of Sponsor  Research institution
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 6   Contact Person  Name of Site  Site Address  Phone/Fax/Email  DrAnant Mohan  All India Institute of Medical Science, New Delhi  Department of Pulmonary, Critical Care & Sleep Medicine, All India Institute of Medical Sciences,Ansari Nagar, New Delhi, Delhi 110029 New Delhi   09810048204 anantmohan@yahoo.com  Dr Rujuta Hadaye  GS medical College & KEM Hospital  Professor, Department of Community Medicine, Seth GSMC and KEM Hospital, Kacharya Donde Marg, Parel, Mumbai, Maharashtra 400012 Mumbai (Suburban)   09869352260 rujutahadaye@gmail.com  DrToteja  ICMR-National Institute for Implementation Research on Non-Communicable Disease, Jodhpur  207, 2nd Flr, Sonal Apt Paota-b Rd Paota, Jodhpur, Rajasthan 342006 Jodhpur   09868368075 gstoteja@gmail.com  DrRRTiwari  ICMR-National Institute for Research in Environmental Health  Director ICMR-National Institute for Research in Environmental Health Bhauri Bypass Rd, Bhopal - 460066 Bhopal   09225224605 tiwari.rr@gov.in  DrCPadmapriyadarsini  ICMR-National Institute for Research in Tuberculosis  Room No. 5, Department of Clinical Research, No.1, Mayor Sathyamoorthy Road Chetput, Chennai Chennai   044-28369539 pcorchids@gmail.com  DrAsha Keetharam  ICMR-National Institute of Occupational Health  Department of clinical epidemiology ICMR-National Institute of Occupational Health, Meghani Nagar, Ahmedabad, Gujarat 380016 Ahmadabad   08197080581 ashaketharam@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 10   Name of Committee  Approval Status  All India Institute of Medical Science, New Delhi  Approved  Amrita Institute of Medical Sciences  Approved  ICMR-National Institute for Implementation Research on Non-Communicable Disease, Jodhpur  Approved  ICMR-National Institute for Research in Environmental Health, Bhopal  Approved  ICMR-National Institute of Occupational Health, Ahmedabad  Approved  JSS Medical College  Approved  KEM Hospital, Mumbai Municipal Corporation of Greater Mumbai  Approved  Mysore Medical College & Reserach Institute  Approved  National Institute for Research in Tuberculosis, Chennai  Approved  Rajarajeswari Medical College Hospital  Approved
Regulatory Clearance Status from DCGI	Status  Notified
Health Condition / Problems Studied	Health Type  Condition  Healthy Human Volunteers  COVID-19
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  BCG vaccine   Single dose of 0.1ml of BCG vaccine given intradermally (BCG-Serum Institute of India) over the distal insertion of the deltoid muscle onto the left humerus (approximately one third down the left upper arm) Frequency : Once Duration of therpay: Once  Comparator Agent  None  No intervention
Inclusion Criteria Modification(s)	Age From  60.00 Year(s) Age To  95.00 Year(s) Gender  Both  Details  1)Elderly individuals 60 years – 95 years of age with general good health, as confirmed by history and physical examination. 2) No known history of HIV or on immunosuppressive drugs for malignancy or transplant 3) Provide a signed and dated informed consent form 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.
ExclusionCriteria	Details  1) Positive for SARS-Cov2 infection, by either antibody (serology) or PCR test 2) Known HIV or malignancy or Transplant recipient or on Dialysis 3) Individuals on immune-suppressive therapies or treatments for malignancy or transplant / dialysis / anti-retroviral treatment 4) Recently (in the last 6-months) diagnosed with TB or currently on anti-TB treatment or anti-psychiatric medications 5) Has any BCG vaccine contraindication like allergy or hypersensitivity to BCG, individuals with HIV infection, leukaemia, malignant lymphoma, chronic granulomatous disease, 6) H/o of previous administration of experimental MTB vaccines within the past 6 months. 7) Sick and moribund individuals with Karnofsky score <50
Method of Generating Random Sequence	Not Applicable
Method of Concealment	Not Applicable
Blinding/Masking	Not Applicable
Primary Outcome	Outcome  TimePoints  Proportion of patients with Severe COVID disease based on COVID Severity Scale and proportion of death due to Covid 19 disease   6 months post vaccination
Secondary Outcome	Outcome  TimePoints  1. Proportion of Hospital admission and ICU admission due to Covid-19 2. Proportion of participants in various Severity stages of Covid-19 (mild, moderate or severe) 3. Proportion of participants requiring hospital admission due to other respiratory febrile illness 4. Immunological outcomes in the sub study   At 6 months post vaccination
Target Sample Size	Total Sample Size="1450" Sample Size from India="1450"
Phase of Trial	N/A
Date of First Enrollment (India)	25/06/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="11" Days="30"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Closed to Recruitment of Participants
Publication Details Modification(s)	Nil
Brief Summary Modification(s)	1. Rationale: SARS-CoV2 viral infection is spreading rapidly throughout the world. A large epidemic in India poses a major threat to the public health system. Elderly individuals, especially those with diabetes, hypertension and other chronic diseases are especially at high risk of mortality. Strategies to protect these individuals are, therefore, 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.   2. Primary objective: To evaluate the effectiveness of BCG vaccination in preventing morbidity due to COVID-19 in elderly individuals between 60 to 80 years of age   living in COVID-19 hotspots in India. Secondary objective: a) To evaluate the effectiveness of BCG vaccination in preventing mortality due to COVID-19 in elderly individuals between 60 to 80 years of age   living in COVID-19 hotspots in India. b) To evaluate the effectiveness of BCG vaccination in reducing the cumulative incidence of hospital admission, intensive Care admission and the incidence of other respiratory febrile illness c) To determine the innate and adaptive immune responses, IgM, IgG and IgA antibody titers and measure biomarkers generated by BCG vaccination  in a subset of individuals.  Study design: Intervention study Study population: Elderly 60 – 80 years of age residing in designated red and orange zones (hotspots) for SARS-Cov2 infection       Study Intervention: One dose of intradermal BCG vaccine.                                         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, New Delhi, Mysuru, Bangluru and Kochi        Study Sample size: 1555 individuals between 60-80 years of age will receive BCG vaccination while 778 individuals will be controls without vaccination       Study duration: Six months per participant. Enrolment at each site will be over: 4 months. Each participant will be followed for 6 months post vaccination           Study Outcomes Primary outcome will be reduction of morbidity and mortality due to COVID-19 disease. Secondary endpoints include cumulative incidence of hospital admission and Intensive Care Admission. We will also look at immunological outcome in a sub-set of study participants. Multivariable regression will be used to produce estimates of vaccine effectiveness adjusted for confounders.