A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants

Prasad S. Kulkarni, Sajjad Desai, Tushar Tewari, Anand Kawade, Nidhi Goyal, Bishan Swarup Garg, Dinesh Kumar, Suman Kanungo, Veena Kamat, Gagandeep Kang, Ashish Bavdekar, Sudhir Babji, Sanjay Juvekar, Byomkesh Manna, Shanta Dutta, Rama Angurana, Deepika Dewan, Abhijeet Dharmadhikari, Jagdish K. Zade, Rajeev M. DhereAlan Fix, Maureen Power, Vidyasagar Uprety, Varsha Parulekar, Iksung Cho, Temsunaro R. Chandola, Vikash K. Kedia, Abhishek Raut, Jorge Flores, Hanif Shaikh, Lalit Gupta, Rakesh Patil, Mohd Aslam, Alok Arya, Farhana Rafiqi, Subodh S. Gupta, Chetna H. Maliye, P. V. Bahulekar, Kiran Bala, Tajali Nazir Shora, Shahid Hussain, Mihir Kumar Bhattacharya, Ashis K. Mukhopadhyay, Dilip Kumar Pal, Jayanta Saha, Ranjitha S. Shetty, Muralidhar M. Kulkarni, Chythra V. Raj, SII BRV-PV author group

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8 weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14 weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p = 0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p = 0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p < 0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p < 0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score ≥ 16) was 60.5% (95% CI 17.7, 81, p = 0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p = 0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).

Original languageEnglish
Pages (from-to)6228-6237
Number of pages10
JournalVaccine
Volume35
Issue number45
DOIs
Publication statusPublished - 27-10-2017

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Rotavirus Vaccines
Phase III Clinical Trials
Rotavirus
clinical trials
Vaccines
Randomized Controlled Trials
vaccines
cattle
placebos
Placebos
India
Gastroenteritis
gastroenteritis
Clinical Trials
House Calls
Intussusception
Developing Countries
Registries
Diarrhea
morbidity

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Kulkarni, P. S., Desai, S., Tewari, T., Kawade, A., Goyal, N., Garg, B. S., ... SII BRV-PV author group (2017). A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine, 35(45), 6228-6237. https://doi.org/10.1016/j.vaccine.2017.09.014
Kulkarni, Prasad S. ; Desai, Sajjad ; Tewari, Tushar ; Kawade, Anand ; Goyal, Nidhi ; Garg, Bishan Swarup ; Kumar, Dinesh ; Kanungo, Suman ; Kamat, Veena ; Kang, Gagandeep ; Bavdekar, Ashish ; Babji, Sudhir ; Juvekar, Sanjay ; Manna, Byomkesh ; Dutta, Shanta ; Angurana, Rama ; Dewan, Deepika ; Dharmadhikari, Abhijeet ; Zade, Jagdish K. ; Dhere, Rajeev M. ; Fix, Alan ; Power, Maureen ; Uprety, Vidyasagar ; Parulekar, Varsha ; Cho, Iksung ; Chandola, Temsunaro R. ; Kedia, Vikash K. ; Raut, Abhishek ; Flores, Jorge ; Shaikh, Hanif ; Gupta, Lalit ; Patil, Rakesh ; Aslam, Mohd ; Arya, Alok ; Rafiqi, Farhana ; Gupta, Subodh S. ; Maliye, Chetna H. ; Bahulekar, P. V. ; Bala, Kiran ; Nazir Shora, Tajali ; Hussain, Shahid ; Kumar Bhattacharya, Mihir ; Mukhopadhyay, Ashis K. ; Kumar Pal, Dilip ; Saha, Jayanta ; Shetty, Ranjitha S. ; Kulkarni, Muralidhar M. ; Raj, Chythra V. ; SII BRV-PV author group. / A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. In: Vaccine. 2017 ; Vol. 35, No. 45. pp. 6228-6237.
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abstract = "Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8 weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14 weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36{\%} (95{\%} CI 11.7, 53.6, p = 0.0067) in the per protocol (PP) analysis, and 41.9{\%} (95{\%} CI 21.1, 57.3, p = 0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5{\%} (95{\%} CI 26.7, 50, p < 0.0001) in the PP analysis and 38.8{\%} (95{\%} CI, 26.4, 49, p < 0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score ≥ 16) was 60.5{\%} (95{\%} CI 17.7, 81, p = 0.0131) at the time of the primary analysis and 54.7{\%} (95{\%} CI 29.7, 70.8, p = 0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).",
author = "Kulkarni, {Prasad S.} and Sajjad Desai and Tushar Tewari and Anand Kawade and Nidhi Goyal and Garg, {Bishan Swarup} and Dinesh Kumar and Suman Kanungo and Veena Kamat and Gagandeep Kang and Ashish Bavdekar and Sudhir Babji and Sanjay Juvekar and Byomkesh Manna and Shanta Dutta and Rama Angurana and Deepika Dewan and Abhijeet Dharmadhikari and Zade, {Jagdish K.} and Dhere, {Rajeev M.} and Alan Fix and Maureen Power and Vidyasagar Uprety and Varsha Parulekar and Iksung Cho and Chandola, {Temsunaro R.} and Kedia, {Vikash K.} and Abhishek Raut and Jorge Flores and Hanif Shaikh and Lalit Gupta and Rakesh Patil and Mohd Aslam and Alok Arya and Farhana Rafiqi and Gupta, {Subodh S.} and Maliye, {Chetna H.} and Bahulekar, {P. V.} and Kiran Bala and {Nazir Shora}, Tajali and Shahid Hussain and {Kumar Bhattacharya}, Mihir and Mukhopadhyay, {Ashis K.} and {Kumar Pal}, Dilip and Jayanta Saha and Shetty, {Ranjitha S.} and Kulkarni, {Muralidhar M.} and Raj, {Chythra V.} and {SII BRV-PV author group}",
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Kulkarni, PS, Desai, S, Tewari, T, Kawade, A, Goyal, N, Garg, BS, Kumar, D, Kanungo, S, Kamat, V, Kang, G, Bavdekar, A, Babji, S, Juvekar, S, Manna, B, Dutta, S, Angurana, R, Dewan, D, Dharmadhikari, A, Zade, JK, Dhere, RM, Fix, A, Power, M, Uprety, V, Parulekar, V, Cho, I, Chandola, TR, Kedia, VK, Raut, A, Flores, J, Shaikh, H, Gupta, L, Patil, R, Aslam, M, Arya, A, Rafiqi, F, Gupta, SS, Maliye, CH, Bahulekar, PV, Bala, K, Nazir Shora, T, Hussain, S, Kumar Bhattacharya, M, Mukhopadhyay, AK, Kumar Pal, D, Saha, J, Shetty, RS, Kulkarni, MM, Raj, CV & SII BRV-PV author group 2017, 'A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants', Vaccine, vol. 35, no. 45, pp. 6228-6237. https://doi.org/10.1016/j.vaccine.2017.09.014

A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. / Kulkarni, Prasad S.; Desai, Sajjad; Tewari, Tushar; Kawade, Anand; Goyal, Nidhi; Garg, Bishan Swarup; Kumar, Dinesh; Kanungo, Suman; Kamat, Veena; Kang, Gagandeep; Bavdekar, Ashish; Babji, Sudhir; Juvekar, Sanjay; Manna, Byomkesh; Dutta, Shanta; Angurana, Rama; Dewan, Deepika; Dharmadhikari, Abhijeet; Zade, Jagdish K.; Dhere, Rajeev M.; Fix, Alan; Power, Maureen; Uprety, Vidyasagar; Parulekar, Varsha; Cho, Iksung; Chandola, Temsunaro R.; Kedia, Vikash K.; Raut, Abhishek; Flores, Jorge; Shaikh, Hanif; Gupta, Lalit; Patil, Rakesh; Aslam, Mohd; Arya, Alok; Rafiqi, Farhana; Gupta, Subodh S.; Maliye, Chetna H.; Bahulekar, P. V.; Bala, Kiran; Nazir Shora, Tajali; Hussain, Shahid; Kumar Bhattacharya, Mihir; Mukhopadhyay, Ashis K.; Kumar Pal, Dilip; Saha, Jayanta; Shetty, Ranjitha S.; Kulkarni, Muralidhar M.; Raj, Chythra V.; SII BRV-PV author group.

In: Vaccine, Vol. 35, No. 45, 27.10.2017, p. 6228-6237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants

AU - Kulkarni, Prasad S.

AU - Desai, Sajjad

AU - Tewari, Tushar

AU - Kawade, Anand

AU - Goyal, Nidhi

AU - Garg, Bishan Swarup

AU - Kumar, Dinesh

AU - Kanungo, Suman

AU - Kamat, Veena

AU - Kang, Gagandeep

AU - Bavdekar, Ashish

AU - Babji, Sudhir

AU - Juvekar, Sanjay

AU - Manna, Byomkesh

AU - Dutta, Shanta

AU - Angurana, Rama

AU - Dewan, Deepika

AU - Dharmadhikari, Abhijeet

AU - Zade, Jagdish K.

AU - Dhere, Rajeev M.

AU - Fix, Alan

AU - Power, Maureen

AU - Uprety, Vidyasagar

AU - Parulekar, Varsha

AU - Cho, Iksung

AU - Chandola, Temsunaro R.

AU - Kedia, Vikash K.

AU - Raut, Abhishek

AU - Flores, Jorge

AU - Shaikh, Hanif

AU - Gupta, Lalit

AU - Patil, Rakesh

AU - Aslam, Mohd

AU - Arya, Alok

AU - Rafiqi, Farhana

AU - Gupta, Subodh S.

AU - Maliye, Chetna H.

AU - Bahulekar, P. V.

AU - Bala, Kiran

AU - Nazir Shora, Tajali

AU - Hussain, Shahid

AU - Kumar Bhattacharya, Mihir

AU - Mukhopadhyay, Ashis K.

AU - Kumar Pal, Dilip

AU - Saha, Jayanta

AU - Shetty, Ranjitha S.

AU - Kulkarni, Muralidhar M.

AU - Raj, Chythra V.

AU - SII BRV-PV author group

PY - 2017/10/27

Y1 - 2017/10/27

N2 - Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8 weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14 weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p = 0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p = 0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p < 0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p < 0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score ≥ 16) was 60.5% (95% CI 17.7, 81, p = 0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p = 0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).

AB - Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8 weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14 weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p = 0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p = 0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p < 0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p < 0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score ≥ 16) was 60.5% (95% CI 17.7, 81, p = 0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p = 0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).

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