MortalityPhase 4AVENIR IINCT06358872
Azithromycin for Child Survival in Niger II
A Phase 4 study testing Azithromycin for Oral Suspension in people with Mortality and Antimicrobial Resistance, run by University of California, San Francisco at 1 site in Niger.
Trial summary
Several randomized controlled trials have demonstrated that azithromycin mass drug administration (MDA) reduces child mortality, but increases antimicrobial resistance (AMR). The World Health Organization (WHO) guidelines for this intervention specify that implementation must be accompanied by continued monitoring of… Read more about this study
- Who is it for?
- Ages 1 month to 59 monthsHealthy volunteers can take part
- Conditions the study is for
- Mortality, Antimicrobial Resistance
- What is being tested?
- Azithromycin for Oral Suspension
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,300,000 participants
- Where
- 1 siteNiger
- Study dates
- 29 Apr 2024to 29 Apr 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 59 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- CSI-level for mortality and AMR monitoring:
- Located in a region participating in the program
- Designated as rural by local study team
- Selected for participation in monitoring activities
- Safe and accessible for study teams
- Verbal approval from community leaders
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- Individual level for mortality monitoring:
- Residing in the catchment area of an eligible CSI
- Selected for participation in monitoring activities
- Female
- Age between 12 and 55 years old
- Verbal approval from participant
- Individual-level for AMR monitoring:
- Residing in the catchment area of an eligible CSI
- Selected for participation in monitoring activities
- Age between 1 and 59 months old
- Verbal approval from a caregiver or guardian
Who cannot join
- At the community-level:
- Designated as urban by local study team
- Inaccessible or unsafe for study team
- At the individual-level:
- Known allergy to macrolides
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Elodie Lebas contact
Niger1 site, 1 recruiting
- Recruiting
Program National de Santé Oculaire
Niamey
Amza Abdou, MD, +011 227-96-96-16-96, dr.amzaabdou@gmail.com
Ahmed Arzika, mamaneahmed@yahoo.fr
About this study
Official title: Azithromycine Pour la Vie Des Enfants au Niger II
Several randomized controlled trials have demonstrated that azithromycin mass drug administration (MDA) reduces child mortality, but increases antimicrobial resistance (AMR). The World Health Organization (WHO) guidelines for this intervention specify that implementation must be accompanied by continued monitoring of mortality and AMR. Niger is expanding the azithromycin MDA program nationwide. To establish monitoring of mortality and AMR as part of this program as well as to leverage the infrastructure to evaluate other child health interventions, AVENIR II is designed as an adaptive platform trial with monitoring and re-randomization every 2 years.
Read the detailed description
AVENIR II is a cluster-randomized adaptive platform trial designed to evaluate community health interventions in Niger. The initial focus is to monitor under-5 mortality and antimicrobial resistance as the azithromycin MDA for child survival program expands in Niger, with the following specific aims:
- Mortality.
- To conduct surveillance of mortality over time compared to the Sustainable Development Goal targets for under-5 mortality reduction. As this intervention is not intended to continue indefinitely, surveillance against a target is needed to determine when to stop.
- To continue to evaluate the effectiveness of azithromycin MDA to reduce under-5 mortality. Given the risk of AMR, the effectiveness of the intervention over time is needed to fully weigh the risks against the benefits.
- Antimicrobial Resistance. To determine the impact of azithromycin MDA on AMR in population- and clinic-based samples.
- Conditions
- Mortality, Antimicrobial Resistance
- Being tested
- Azithromycin for Oral Suspension
- Keywords
- Mass Treatment, Azithromycin, Childhood Mortality Rate, Antimicrobial Resistance, Implementation and Cost Analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin for Oral SuspensionDrug
Also called Zithromax
Azithromycin will be administered as a single dose, in oral suspension form for children. The dose will be calculated by age or height depending on the child's age Both dosing cups and syringes will be used to administer treatment. For children too young to drink out of a dosing cup, a 1 ml or 5 ml syringe will be used, and the calculated dose will be rounded upwards to the nearest 0.2 ml.
| Study group | Role | What they receive |
|---|---|---|
| Continuous Distribution | Active comparator | Azithromycin distribution to children 1-59 months of age for four years using a door-to-door delivery approach via existing community health workers Receives: Drug: Azithromycin for Oral Suspension |
| Delayed Distribution | Active comparator | Delayed, by two years, azithromycin distribution to children 1-59 months of age using a door-to-door delivery approach via existing community health workers Receives: Drug: Azithromycin for Oral Suspension |
| Stop Distribution | Active comparator | Stopping azithromycin distribution after two years to children 1-59 months of age using a door-to-door delivery approach via existing community health workers Receives: Drug: Azithromycin for Oral Suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality
Under-5 mortality rate (U5MR, deaths per 1,000 live births) assessed by pregnancy history at 2 years from the first treatment distribution, comparing the intervention and delayed arms
Measured: 2 years
All-cause mortality
Under-5 mortality rate (U5MR, deaths per 1,000 live births) assessed by pregnancy history at 4 years, comparing the continue and stop arms
Measured: 4 years
Prevalence of resistance to macrolides - nasopharyngeal swabs
Prevalence of macrolide-resistant pneumococcus from nasopharyngeal swabs in children 1-59 months old after 2 years of distributions, comparing the intervention and delayed arms
Measured: 2 years
Prevalence of resistance to macrolides - nasopharyngeal swabs
Prevalence of macrolide-resistant pneumococcus from nasopharyngeal swabs in children 1-59 months old after 4 years of distributions, comparing the continue and stop arms
Measured: 4 years
Load of genetic determinants of resistance to macrolides - rectal swabs
Load of genetic determinants of resistance to macrolides from rectal swabs in children 1-59 months old after 2 years of distributions, comparing the intervention and delayed arms
Measured: 2 years
Load of genetic determinants of resistance to macrolides - rectal swabs
Load of genetic determinants of resistance to macrolides from rectal swabs in children 1-59 months old after 4 years of distributions, comparing the continue and stop arms
Measured: 4 years
Secondary outcomes (6)
Number of clinic visits - infectious
All infectious clinic visits among children 1-59 months of age in the program catchment area during the distribution period as assessed through passive surveillance of CSI records
Measured: 2 years
Number of clinic visits - infectious
All infectious clinic visits among children 1-59 months of age in the program catchment area during the distribution period as assessed through passive surveillance of CSI records
Measured: 4 years
Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs
Prevalence of genetic determinants of resistance from nasopharyngeal swabs in children 1-59 months old after 2 years of distributions, comparing the intervention and delayed arms
Measured: 2 years
Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs
Prevalence of genetic determinants of resistance from nasopharyngeal swabs in children 1-59 months old after 4 years of distributions, comparing the continue and stop arms
Measured: 4 years
Program Cost Per Dose Delivered
Program costs will be tracked using routine expenditure reporting and micro-costing activities.
Measured: 2 years
Prevalence of Reported Illness
Prevalence of caregiver reported illness among children 1-59 months of age in the program's catchment area in the 2 weeks following MDA as assessed through a household survey in a random subset of the population
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2024
- Study start29 Apr 2024
- Primary completion29 Apr 2028 (estimated)
- Study completion29 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for MortalityStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The intervention will involve biannual oral azithromycin MDA to children 1-59 months old distributed by community health workers. The Centre de Santé Integré (CSI) will be randomized to receive azithromycin MDA or delayed treatment in a stepped wedge design for the first 2 years. The delayed intervention arm will receive usual care for the first 2 years, then will receive the intervention for the next 2 years.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3,300,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de recherche et interventions en santé publique (CRISP), Ministère de la Santé Publique du Niger, Le Programme National de Santé Oculaire, Centre de Recherche Médicale et Sanitaire, Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Kieran S O'Brien, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06358872
- Sponsor's protocol ID
- 23-39839
- Acronym
- AVENIR II
- Status last verified
- Aug 2026
- First submitted
- 3 Apr 2024
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data underlying outcomes publications will be made publicly available.
Publications
Oldenburg CE, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Zakane A, Coulibaly B, Bagagnan C, Hu H, O'Brien KS, Nyatigo F, Keenan JD, Doan T, Porco TC, Arnold BF, Lebas E, Sie A, Lietman TM. Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial. JAMA. 2024 Feb 13;331(6):482-490. doi: 10.1001/jama.2023.27393.
PubMed 38349371Sie A, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Bagagnan C, Lebas E, Hu H, Rice J, Porco TC, Arnold BF, Lietman TM, Oldenburg CE. Azithromycin during Routine Well-Infant Visits to Prevent Death. N Engl J Med. 2024 Jan 18;390(3):221-229. doi: 10.1056/NEJMoa2309495.
PubMed 38231623Chao DL, Arzika AM, Abdou A, Maliki R, Karamba A, Galo N, Beidi D, Harouna N, Abarchi M, Root E, Mishra A, Lebas E, Arnold BF, Oldenburg CE, Keenan JD, Lietman TM, O'Brien KS. Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2346840. doi: 10.1001/jamanetworkopen.2023.46840.
PubMed 38100110Keenan JD, Ayele B, Gebre T, Zerihun M, Zhou Z, House JI, Gaynor BD, Porco TC, Emerson PM, Lietman TM. Childhood mortality in a cohort treated with mass azithromycin for trachoma. Clin Infect Dis. 2011 Apr 1;52(7):883-8. doi: 10.1093/cid/cir069.
PubMed 21427395O'Brien KS, Cotter SY, Amza A, Kadri B, Nassirou B, Stoller NE, Zhou Z, West SK, Bailey RL, Keenan JD, Porco TC, Lietman TM. Childhood Mortality After Mass Distribution of Azithromycin: A Secondary Analysis of the PRET Cluster-randomized Trial in Niger. Pediatr Infect Dis J. 2018 Nov;37(11):1082-1086. doi: 10.1097/INF.0000000000001992.
PubMed 29561511Keenan JD, Bailey RL, West SK, Arzika AM, Hart J, Weaver J, Kalua K, Mrango Z, Ray KJ, Cook C, Lebas E, O'Brien KS, Emerson PM, Porco TC, Lietman TM; MORDOR Study Group. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. N Engl J Med. 2018 Apr 26;378(17):1583-1592. doi: 10.1056/NEJMoa1715474.
PubMed 29694816Doan T, Hinterwirth A, Worden L, Arzika AM, Maliki R, Abdou A, Kane S, Zhong L, Cummings ME, Sakar S, Chen C, Cook C, Lebas E, Chow ED, Nachamkin I, Porco TC, Keenan JD, Lietman TM. Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution. Nat Med. 2019 Sep;25(9):1370-1376. doi: 10.1038/s41591-019-0533-0. Epub 2019 Aug 12.
PubMed 31406349Keenan JD, Arzika AM, Maliki R, Elh Adamou S, Ibrahim F, Kiemago M, Galo NF, Lebas E, Cook C, Vanderschelden B, Bailey RL, West SK, Porco TC, Lietman TM; MORDOR-Niger Study Group. Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial. Lancet Glob Health. 2020 Feb;8(2):e288-e295. doi: 10.1016/S2214-109X(19)30540-6.
PubMed 31981558WHO Guideline on Mass Drug Administration of Azithromycin to Children under Five Years of Age to Promote Child Survival [Internet]. Geneva: World Health Organization; 2020. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK561641/
PubMed 32924384Doan T, Worden L, Hinterwirth A, Arzika AM, Maliki R, Abdou A, Zhong L, Chen C, Cook C, Lebas E, O'Brien KS, Oldenburg CE, Chow ED, Porco TC, Lipsitch M, Keenan JD, Lietman TM. Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution. N Engl J Med. 2020 Nov 12;383(20):1941-1950. doi: 10.1056/NEJMoa2002606.
PubMed 33176084Arzika AM, Amza A, Ousmane S, Maliki R, Almou I, Galo N, Harouna N, Mankara A, Aichatou B, Boubacar O, Lebas E, Peterson B, Brandt C, Picariello A, Cheng A, Porco TC, Doan T, Arnold BF, Lietman TM, O'Brien KS. Azithromycin mass drug administration to reduce child mortality in Niger (AVENIR II): a master protocol for a cluster-randomized adaptive platform trial to evaluate community-based health interventions. Trials. 2026 Feb 18;27(1):235. doi: 10.1186/s13063-026-09561-2.
PubMed 41709349Arzika AM, Amza A, Ousmane S, Maliki R, Almou I, Galo N, Harouna N, Mankara A, Aichatou B, Boubacar O, Lebas E, Peterson B, Brandt C, Picariello A, Cheng A, Porco TC, Doan T, Arnold BF, Lietman TM, O'Brien KS. Azithromycin mass drug administration to reduce child mortality in Niger (AVENIR II): a master protocol for a cluster-randomized adaptive platform trial to evaluate community-based health interventions. medRxiv [Preprint]. 2025 Jun 18:2025.06.17.25329431. doi: 10.1101/2025.06.17.25329431.
PubMed 40585143