CTRI Number	CTRI/2020/07/026668 [Registered on: 18/07/2020] Trial Registered Prospectively
Last Modified On:	03/02/2021
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Vaccine Preventive
Study Design	Randomized, Parallel Group, Placebo Controlled Trial
Public Title of Study Modification(s)	To study the effect of BCG vaccine in Reducing the Incidence and severity of COVID-19 in the high-risk population
Scientific Title of Study Modification(s)	To evaluate efficacy of Bacillus Calmette-Guerin (BCG) in Reducing the Incidence and severity of COVID-19 in the high-risk population (BRIC): a phase III, Multicentric, Quadruple blind Randomized controlled trial
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Dr Sanjeev Sinha  Address  Third floor, RN 17, SRB wing, Department of Medicine, Ansari Nagar, AIIMS, New Delhi E-61. Ansari Nagar East AIIMS, New Delhi-110029 New Delhi DELHI 110029 India  Phone  9810164416   Fax  011-26588918   Email  drsanjeevsinha@gmail.com
Details Contact Person Scientific Query Modification(s)	Name  Dr Sanjeev Sinha  Address  Third floor, RN 17, SRB wing, Department of Medicine, Ansari Nagar, AIIMS, New Delhi E-61, Ansari Nagar East, AIIMS, New Delhi-110029 New Delhi DELHI 110029 India  Phone  9810164416   Fax  011-26588918   Email  drsanjeevsinha@gmail.com
Details Contact Person Public Query Modification(s)	Name  Dr Sanjeev Sinha  Address  Third floor, RN 17, SRB wing, Department of Medicine, Ansari Nagar, AIIMS, New Delhi E-61, Ansari Nagar, East, AIIMS, New Delhi-110029 New Delhi DELHI 110029 India  Phone  9810164416   Fax  011-26588918   Email  drsanjeevsinha@gmail.com
Source of Monetary or Material Support Modification(s)	Indian Council of Medical Research V. Ramalingaswami Bhawan, Ansari Nagar, P.Box No. 4911 New Delhi – 110029
Primary Sponsor	Name  Indian Council of Medical Research  Address  Indian Council of Medical Research, V. Ramalingaswami Bhawan, Ansari Nagar, P.Box No. 4911 New Delhi – 110029   Type of Sponsor  Government funding agency
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 3   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Sanjeev Sinha  AIIMS, New Delhi  Room number 17, SRB wing, third floor, Department of Medicine, AIIMS, New Delhi-110029 New Delhi   9810164416 011-26588918 drsanjeevsinha@gmail.com  Dr Sushil Gupta  Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow   Second floor, Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Rai Bareli Road, Lucknow Lucknow   0522-2494395 0522-2668017 sushilguptasgpgi@gmail.com  Dr SK Guha  School of Tropical Medicine, Kolkata  Second floor, Department of Tropical Medicine, School of Tropical Medicine, 108, Chittaranjan Avenue, Kolkata, West Bengal- 700073 Kolkata   9831234802 9831234802 drskguha@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 3   Name of Committee  Approval Status  Clinical Research Ethics Committee (CREC-STM) Calcutta School of Tropical Medicine  Approved  Ethics Committee, AIIMS  Approved  SGPGI Lucknow  Submittted/Under Review
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Coronavirus as the cause of diseases classified elsewhere
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  Conventional BCG vaccine  Standard COVID-19 preventive practices along with BCG Vaccine. Participants will receive a single dose of BCG vaccine at base line. The adult dose of BCG vaccine is 0.1 mL injected intradermally over the distal insertion of the deltoid muscle in left arm.We will follow them for 9 months.   Comparator Agent  Standard COVID-19 preventive practices along with Inj Placebo (saline). Participants will receive a single dose will consist of 0.1 mL saline at baseline.   The adult dose of BCG vaccine is 0.1 mL injected intradermally over the distal insertion of the deltoid muscle in left arm.We will follow them for 9 months.
Inclusion Criteria	Age From  18.00 Year(s) Age To  60.00 Year(s) Gender  Both  Details  I. High-risk groups which include: adults (Male and female ≥18 to 60 years) with underlying medical conditions, particularly if not well controlled, including: 1. Diabetes mellitus 2. Chronic kidney disease (both dialysis dependent and independent) 3. Chronic heart conditions (coronary artery disease and hypertension) 4. Chronic lung disease (included asthma, COPD and bronchiectasis)
ExclusionCriteria	Details  i. History of allergy to (components of) the BCG vaccine or serious adverse events to prior BCG administration ii. Any signs or symptoms of COVID-19 within the past 24 hours iii. Pregnancy or planning pregnancy iv. Breastfeeding v. Suspicion of active viral or bacterial infection vi. Any Immunocompromised subjects including o Human immunodeficiency virus (HIV-1), o Neutropenic with less than 1500 neutrophils/mm3, o Solid organ or bone marrow transplantation, o Chemotherapy or radiotherapy, and o Primary immunodeficiency vii. Subject on immunosuppressed or taking immunosuppressive drugs viii. Documented history of COVID-19 infection ix. Active malignancy within the prior two years o Active skin disease such as eczema, dermatitis or psoriasis at or near site of vaccination o Direct involvement in the design or the execution of the study o Not willing to give consent
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	On-site computer system
Blinding/Masking	Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome	Outcome  TimePoints  Incidence of COVID-19 by 9 months of follow-up.  Incidence of COVID-19 by 9 months of follow-up.
Secondary Outcome	Outcome  TimePoints  1. Incidence of severe COVID-19 by 9 months of follow-up. 2. Incidence of Adverse events following immunization (AEFIs) associated with BCG vaccine. 3. The change of titers of PPD-specific IgM and IgG following BCG vaccination   9 months
Target Sample Size	Total Sample Size="800" Sample Size from India="800"
Phase of Trial	N/A
Date of First Enrollment (India)	05/08/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Open to Recruitment
Publication Details	nil
Brief Summary Modification(s)	Title of the project:  : “To evaluate efficacy of Bacillus Calmette-Guerin (BCG) in Reducing the Incidence and severity of COVID-19 in the high-risk population (BRIC): a phase III, Multicentric, Quadruple blind Randomized controlled trial”.   Objectives: Primary: 1.    To evaluate efficacy of BCG vaccine as an adjunct to standard prevention practices in reducing the incidence of COVID-19 in the high-risk individuals. Secondary: 1.    To evaluate efficacy of BCG vaccine as an adjunct to standard prevention practices in reducing the incidence of severe COVID-19 in the high-risk individuals. Summary:          Background:                 On December 2019 the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China’s Hubei province, during an outbreak of viral pneumonia. Some epidemiological studies have proposed universal policies of BCG vaccination may have reduced the number of reported COVID-19 cases in a country. This makes a combined strategy of universal BCG vaccination and combination of healthcare safety may reduce morbidity and mortality. However, the association between vaccine-induced cell-mediated immunity and protection against COVID-19 is unclear. Novelty:              As the previous studies suggest high-risk population which include adults with comorbidities (like hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, chronic lung disease, and chronic kidney diseases, chronic liver diseases, and malignancy) are at higher risk of SARS-CoV-2 infection. BCG vaccine effectively induces T-helper 1 (Th1) that secrete high levels of IFN-γ and that are active against intracellular pathogens. Recently described, a memory phenotype in innate immune cells, known as “trained immunity”. BCG vaccine induces “trained immunity” thus, providing may provide non-specific protection against respiratory infections. Methods: Study Type: Interventional (Clinical Trial) Estimated Enrolments: 800 (from all sites) Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Phase III, two group, multicentric, Quadruple blind Randomized controlled trial Masking: Quadruple blind Randomized controlled trial Primary Purpose: Prevention   Study End points: a Primary end point: 1.    Reduction in incidence of COVID-19          b Secondary end point: 1.    Reduction in incidence of severe pneumonia and ARDS related to COVID-19 2.    Reduction in incidence of hospital admission and intensive care admission related to COVID-19 3.    To see the safety of BCG vaccine for prevention and incidence of COVID-19 *** COVID-19 case defined as per Revised Guidelines on Clinical Management of COVID-19 by Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) Keywords: COVID-19, Bacillus Calmette-Guerin (BCG) vaccine, Prevention, and randomized controlled trial