TY - JOUR
T1 - Age-based targeting of biannual azithromycin distribution for child survival in Niger
T2 - an adaptive cluster-randomized trial protocol (AVENIR)
AU - the AVENIR Study Group
AU - O’Brien, Kieran S.
AU - Arzika, Ahmed M.
AU - Amza, Abdou
AU - Maliki, Ramatou
AU - Ousmane, Sani
AU - Kadri, Boubacar
AU - Nassirou, Beido
AU - Mankara, Alio Karamba
AU - Harouna, Abdoul Naser
AU - Colby, Emily
AU - Lebas, Elodie
AU - Liu, Zijun
AU - Le, Victoria
AU - Nguyen, William
AU - Keenan, Jeremy D.
AU - Oldenburg, Catherine E.
AU - Porco, Travis C.
AU - Doan, Thuy
AU - Arnold, Benjamin F.
AU - Lietman, Thomas M.
AU - De Borman, Nicolas
AU - Dresse, Stephane
AU - Olekhnovitch, Romain
AU - Lurton, Grégoire
AU - Monchy, Léa
AU - De Wulf, Martin
AU - Brander, Rebecca
AU - Chao, Dennis
AU - Heine, James
AU - Izadnegahdar, Rasa
AU - Lamberti, Laura
AU - Oron, Assaf
AU - Rajaram, Surabhi
AU - Steele, Matthew
AU - Seyfoule, Amina
AU - Arzika, Ahmed
AU - Bello, Fati
AU - Boubacar, Diallo
AU - Harouna, Amadou
AU - Karamba, Alio
AU - Nomao, Farissat
AU - Omar, Abraham
AU - Issa, Ibrahima
AU - Jambou, Ronan
AU - Labbo, Rabiou
AU - Lamine, S’ Hooshim N.
AU - Rakia, Boubakar
AU - Sadikou, Maikano
AU - Amouzou, Agbessi
AU - Black, Robert
N1 - Funding Information:
This work was supported by the Bill & Melinda Gates Foundation grants OPP1210548 and INV-002454, the Peierls Foundation, Research to Prevent Blindness, and That Man May See. Pfizer donated azithromycin and placebo for the trial. The Bill & Melinda Gates Foundation reviewed and approved the study design. The funders had no role in study implementation, data collection, analysis, or preparation of this manuscript.
Funding Information:
The authors would like to acknowledge the AVENIR study group for their many contributions to this work: Bluesquare, Brussels, Belgium ? Nicolas De Borman, Stephane Dresse, Romain Olekhnovitch, Gr?goire Lurton, L?a Monchy, Martin De Wulf; Bill & Melinda Gates Foundation, Seattle, WA, USA ? Rebecca Brander, Dennis Chao, James Heine, Rasa Izadnegahdar, Laura Lamberti, Assaf Oron, Surabhi Rajaram, Matthew Steele; Centre de m?re et d?enfant, Dosso, Niger ? Amina Seyfoule; Centre de recherche et interventions en sant? publique, Niamey, Niger ? Ahmed Arzika, Fati Bello, Diallo Boubacar, Amadou Harouna, Alio Karamba, Ramatou Maliki, Farissat Nomao, Abraham Omar; Centre de recherche m?dical et sanitaire, Niamey, Niger ? Ibrahima Issa, Ronan Jambou, Rabiou Labbo, S?Hooshim N. Lamine, Sani Ousmane, Boubakar Rakia, Maikano Sadikou; ClinEpiDB, Philadelphia, PA, USA ? Brianna Lindsay, Nupur Kittur, David Roos, Sheena Tomko; Comit? national ?thique pour la recherhce en sant?, Niamey, Niger ? Issa Adji, Djibo Ali, Souleymane Alzouma, Maidanda Boubacar, Diegou Boureima, Cheik Boureima Daouda, Idi Moussa Djatao, Ibrahim Jean Etienne, El Hadji Boubakar H Maiga, Amadou Oumarou, Ocquet Sakina, Sanoussi Samuila; Data and Safety Monitoring Committee ? Emory University, Task Force for Global Health ? David Addiss; Niger Ministry of Health ? Mourtala Assao; St. George?s University of London ? Julia Bielicki, Retired from CDC ? Allen Hightower, Children?s Hospital of Colorado ? Brian Jackson, University of Melbourne ? Fiona Russell; Global Health Strategies, New York, NY, USA ? Frances Hocking, Zied Mhirsi, Dan Pawson; Johns Hopkins University, Baltimore, MA, USA ? Agbessi Amouzou, Robert Black; Pfizer, New York, NY, USA ? Waqas Ahmed, Todd D. Hatajik, Julie Jenson, Chuck Knirsch, Chiao-Chin Lin; Programme national de sant? oculaire, Niamey, Niger ? Amza Abdou, Nassirou Beido, Boubacar Kadri, Boubacar Ma?danda; Speak Up Africa, Dakar, Senegal ? Maelle Ba, Yaye Sophi?tou Diop, Yacine Djibo, Gr?inne Hutton, Fara Ndiaye; University of California, San Francisco, San Francisco, CA, USA ? Benjamin Arnold, Cindi Chen, Emily Colby, Catherine A Cook, Thuy Doan, Jeremy D Keenan, Victoria Le, Elodie Lebas, Thomas M Lietman, Zijun Liu, William Nguyen, Kieran S O?Brien, Catherine E Oldenburg, Travis C Porco, Kevin Ruder, George W Rutherford, Lina Zhong, Zhaoxia Zhou; UCSF-UC Berkeley Center for Global Health Development, Diplomacy, and Economics, CA, USA ? Stefano M. Bertozzi, Jim G. Khan, Elliot Marseille; University of Southampton, Southampton, United Kingdom ? Gianluca Boo, Edith Darin, Andy Tatem.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - Adaptive trial
KW - Azithromycin
KW - Cluster-randomized trial
KW - Mass drug administration
KW - Mortality
UR - http://www.scopus.com/inward/record.url?scp=85105179356&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105179356&partnerID=8YFLogxK
U2 - 10.1186/s12889-021-10824-7
DO - 10.1186/s12889-021-10824-7
M3 - Article
C2 - 33926403
AN - SCOPUS:85105179356
VL - 21
JO - BMC Public Health
JF - BMC Public Health
SN - 1471-2458
IS - 1
M1 - 822
ER -