BMJ Open (Aug 2024)

PreVenTB trial: protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: phase III, randomised, double-blind, three-arm placebo-controlled trial

  • ,
  • Raman R Gangakhedkar,
  • Ravindra Mohan Pandey,
  • Rakesh Kumar,
  • Randeep Guleria,
  • Manjula Singh,
  • Soumya Swaminathan,
  • George D’Souza,
  • Rashmi Rodrigues,
  • Anand Krishnan,
  • Sanghamitra Pati,
  • Sudipta Mohakud,
  • Anant Mohan,
  • Ramesh Kumar,
  • Prasanta Raghab Mohapatra,
  • Parul Kodan,
  • Rohit Sarin,
  • Baijayantimala Mishra,
  • Geeta Yadav,
  • Deepak Gupta,
  • Anuj Bhatnagar,
  • Sriram Selvaraju,
  • Ritu Gupta,
  • Sandeep Patil,
  • Sourin Bhuniya,
  • Sanjay Mehendale,
  • Samiran Panda,
  • Subrata Kumar Palo,
  • Debasish Hota,
  • Sangeeta Sharma,
  • Srikanth Tripathy,
  • Kiran Katoch,
  • Sindhu Joshi,
  • Somashekar Narasimhaiah,
  • Sangeeta Bhaskar,
  • Rajni Rani,
  • Abdul Mabood Khan,
  • Urvashi B Singh,
  • D K Mitra,
  • Neelam Roy,
  • Amitva Sen Gupta,
  • Vikram Vohra,
  • Neeta Singla,
  • Vijaya Valluri Ansari,
  • Chitra Iravatham,
  • Shilpa Rakh,
  • D K Prudhula,
  • Chala Devi,
  • N Rupa,
  • K Sailaja,
  • Sheela Godbole,
  • Seema Sahay,
  • Suchit Kamble,
  • Megha Mamulwar,
  • Arati Kishor Mane,
  • Ashwini Vinod Shete,
  • Abhijit Vasantrao Kadam,
  • Vineet Chadha,
  • S Uma Shankar,
  • C Ravichandra,
  • S K Tripathy,
  • Dasarathi Das,
  • Tahziba Hussain,
  • B Dwibedi,
  • P R Mohapatra,
  • S C B Cuttack,
  • M R Pattnaik,
  • Sabita Mohapatra,
  • Banu Rekha,
  • Mohan Natarajan,
  • P K Bhavani,
  • D Bella Devaleenal,
  • Syed Hisar,
  • S Devarajulu Reddy,
  • Paul Kumaran,
  • Makhesh Kumar,
  • Poorna Ganga Devi,
  • Sunny Omkar Singh,
  • Devi Pratyush,
  • Vidushi Gupta,
  • Parvathi

DOI
https://doi.org/10.1136/bmjopen-2023-082916
Journal volume & issue
Vol. 14, no. 8

Abstract

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Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.