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Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR)

Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR)
Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR)

Background: biannual distribution of azithromycin to children 1–59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1–11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. 

Methods: AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1–11: biannual azithromycin to children 1–11 months old with placebo to children 12–59 months old, 2) azithromycin 1–59: biannual azithromycin to children 1–59 months old, or 3) placebo: biannual placebo to children 1–59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1–59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1–59 months old comparing the azithromycin 1–59 and placebo arms, 2) children 1–11 months old comparing the azithromycin 1–11 and placebo arm, and 3) children 12–59 months in the azithromycin 1–11 and azithromycin 1–59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1–59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1–59 months old. 

Discussion: as high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. Trial registration: This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987).

Adaptive trial, Azithromycin, Cluster-randomized trial, Mass drug administration, Mortality
1471-2458
O’Brien, Kieran S.
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Dresse, Stephane
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Monchy, Léa
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De Wulf, Martin
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Brander, Rebecca
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Chao, Dennis
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Heine, James
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Izadnegahdar, Rasa
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Lamberti, Laura
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Oron, Assaf
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Rajaram, Surabhi
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Steele, Matthew
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Seyfoule, Amina
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Arzika, Ahmed
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Bello, Fati
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Boubacar, Diallo
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Harouna, Amadou
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Karamba, Alio
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Nomao, Farissat
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Omar, Abraham
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Issa, Ibrahima
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Jambou, Ronan
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Labbo, Rabiou
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Lamine, S’ Hooshim N.
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Rakia, Boubakar
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Boo, Gianluca
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Darin, Edith
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the AVENIR Study Group
O’Brien, Kieran S.
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Arzika, Ahmed M.
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Amza, Abdou
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Maliki, Ramatou
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Ousmane, Sani
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Nassirou, Beido
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Mankara, Alio Karamba
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Harouna, Abdoul Naser
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Colby, Emily
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Lebas, Elodie
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Liu, Zijun
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Le, Victoria
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Nguyen, William
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Keenan, Jeremy D.
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Oldenburg, Catherine E.
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Porco, Travis C.
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Doan, Thuy
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Arnold, Benjamin F.
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Lietman, Thomas M.
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Chao, Dennis
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Heine, James
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Rajaram, Surabhi
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Arzika, Ahmed
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Boubacar, Diallo
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Harouna, Amadou
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Karamba, Alio
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Issa, Ibrahima
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Jambou, Ronan
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Labbo, Rabiou
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Lamine, S’ Hooshim N.
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Rakia, Boubakar
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Boo, Gianluca
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Darin, Edith
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Tatem, Andy
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O’Brien, Kieran S., Arzika, Ahmed M., Amza, Abdou, Maliki, Ramatou, Ousmane, Sani, Kadri, Boubacar, Nassirou, Beido, Mankara, Alio Karamba, Harouna, Abdoul Naser, Colby, Emily, Lebas, Elodie, Liu, Zijun, Le, Victoria, Nguyen, William, Keenan, Jeremy D., Oldenburg, Catherine E., Porco, Travis C., Doan, Thuy, Arnold, Benjamin F. and Lietman, Thomas M. , the AVENIR Study Group (2021) Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR). BMC Public Health, 21 (1), [822]. (doi:10.1186/s12889-021-10824-7).

Record type: Article

Abstract

Background: biannual distribution of azithromycin to children 1–59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1–11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. 

Methods: AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1–11: biannual azithromycin to children 1–11 months old with placebo to children 12–59 months old, 2) azithromycin 1–59: biannual azithromycin to children 1–59 months old, or 3) placebo: biannual placebo to children 1–59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1–59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1–59 months old comparing the azithromycin 1–59 and placebo arms, 2) children 1–11 months old comparing the azithromycin 1–11 and placebo arm, and 3) children 12–59 months in the azithromycin 1–11 and azithromycin 1–59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1–59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1–59 months old. 

Discussion: as high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. Trial registration: This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987).

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Accepted/In Press date: 13 April 2021
Published date: 29 April 2021
Keywords: Adaptive trial, Azithromycin, Cluster-randomized trial, Mass drug administration, Mortality

Identifiers

Local EPrints ID: 488247
URI: http://eprints.soton.ac.uk/id/eprint/488247
ISSN: 1471-2458
PURE UUID: 2411f9e1-eb98-4373-a669-d9c1e8abaebe
ORCID for Gianluca Boo: ORCID iD orcid.org/0000-0002-4078-8221
ORCID for Edith Darin: ORCID iD orcid.org/0000-0002-8176-092X
ORCID for Andy Tatem: ORCID iD orcid.org/0000-0002-7270-941X

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Date deposited: 19 Mar 2024 17:37
Last modified: 01 Aug 2024 01:56

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Contributors

Author: Kieran S. O’Brien
Author: Ahmed M. Arzika
Author: Abdou Amza
Author: Ramatou Maliki
Author: Sani Ousmane
Author: Boubacar Kadri
Author: Beido Nassirou
Author: Alio Karamba Mankara
Author: Abdoul Naser Harouna
Author: Emily Colby
Author: Elodie Lebas
Author: Zijun Liu
Author: Victoria Le
Author: William Nguyen
Author: Jeremy D. Keenan
Author: Catherine E. Oldenburg
Author: Travis C. Porco
Author: Thuy Doan
Author: Benjamin F. Arnold
Author: Thomas M. Lietman
Author: Nicolas De Borman
Author: Stephane Dresse
Author: Romain Olekhnovitch
Author: Grégoire Lurton
Author: Léa Monchy
Author: Martin De Wulf
Author: Rebecca Brander
Author: Dennis Chao
Author: James Heine
Author: Rasa Izadnegahdar
Author: Laura Lamberti
Author: Assaf Oron
Author: Surabhi Rajaram
Author: Matthew Steele
Author: Amina Seyfoule
Author: Ahmed Arzika
Author: Fati Bello
Author: Diallo Boubacar
Author: Amadou Harouna
Author: Alio Karamba
Author: Farissat Nomao
Author: Abraham Omar
Author: Ibrahima Issa
Author: Ronan Jambou
Author: Rabiou Labbo
Author: S’ Hooshim N. Lamine
Author: Boubakar Rakia
Author: Gianluca Boo ORCID iD
Author: Edith Darin ORCID iD
Author: Andy Tatem ORCID iD
Corporate Author: the AVENIR Study Group

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