MortalityPhase 4AVENIRNCT04224987
Azithromycin for Child Survival in Niger: Mortality and Resistance Trial
A Phase 4 study testing Azithromycin in people with Mortality and Resistance Bacterial, run by University of California, San Francisco at 1 site in Niger.
Trial summary
The MORDOR trial found that biannual distribution of azithromycin to children 1-59 months old reduced child mortality. The World Health Organization (WHO) released conditional guidelines for this intervention, which include targeting azithromycin distributions to children 1-11 months of age in high mortality… 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, Resistance Bacterial, Child, Only
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 864,493 participants
- Where
- 1 siteNiger
- Study dates
- 24 Nov 2020to 31 Jul 2024
- 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
- Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions
- Population 250 to 2,499*
- Distance > 5 km from district headquarters town
- Distinguishable from neighboring communities
- Verbal consent of community leader(s)
- Age 1-59 months
Show all 15Show fewer
- Primary residence in a study community
- Verbal consent of caregiver/guardian for study participation
- Weight ≥ 3.0 kg (*no weight limits in communities using age-based dosing)
- Location in Dosso
- Distinguishable from neighboring communities
- Verbal consent of community leader(s)
- Age 1-59 months or 7-12 years or caregiver/guardian of a child eligible for treatment
- Primary residence in a study community selected for sample collections
- Verbal consent of caregiver/guardian for study participation
Who cannot join
- Inaccessible or unsafe for study team
- "Quartier" designation on national census *Population size as estimated from the most recent national census or projections
- At the individual-level, eligibility includes:
- Known allergy to macrolides
- Population-based sample collections
- At the community-level, eligibility includes:
Show all 12Show fewer
- Inaccessible or unsafe for the study team
- Included in MORDOR trials
- Not randomly selected
- Received treatment prior to sample collection
- At the individual-level, eligibility includes:
- An individual is not on the list of randomly selected participants from the census
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Azithromycine Pour la Vie Des Enfants au Niger - Implémentation et Recherche: Essai mortalité et résistance (Azithromycin for Child Survival in Niger: Mortality Trial and Resistance Trial)
The MORDOR trial found that biannual distribution of azithromycin to children 1-59 months old reduced child mortality. The World Health Organization (WHO) released conditional guidelines for this intervention, which include targeting azithromycin distributions to children 1-11 months of age in high mortality settings.Targeting treatment to children 1-11 months old could reduce antimicrobial resistance by limiting antibiotic distributions while treating children at the highest mortality risk. However, this targeted intervention has not yet been tested.
The AVENIR mortality/resistance trial aims to assess the efficacy of age-based targeting of biannual azithromycin distribution on mortality as well as determine the impact of age-based targeting on antimicrobial resistance.
Read the detailed description
In the Mortality/Resistance trial, 3,000 communities in the Dosso and Tahoua regions of Niger will be randomized to one of three arms: 1) azithro 1-11: biannual oral azithromycin to children 1-11 months old with biannual oral placebo to children 12-59 months old, 2) azithro 1-59: biannual oral azithromycin to children 1-59 months old, or 3) placebo: biannual oral placebo to children 1-59 months old. Interventions will be delivered biannually through a door-to-door census. Mortality will also be monitored through biannual census data collection, which will be used to adaptively allocate treatment assignments after the first year. Communities will retain an allocation for 4 distributions before being re-randomized.
Antimicrobial resistance will be monitored using cluster sampling of treated and untreated children and adults in the Dosso region.
To compare costs, coverage, and acceptability of treating 1-11-month-old children only vs children 1-59 months old, an additional 80 communities in the Dosso region will be selected. These communities will be randomized in a 1:1 fashion to either receive 1) distribution of open-label azithromycin to children 1-11 months old with no intervention to children 12-59 months old or 2) distribution of open-label azithromycin to children 1-59 months old. The primary outcome for this substudy will be community-level costs per dose delivered. Secondary outcomes include program costs, treatment coverage, and acceptability of the intervention according to community leaders, community health workers, and caregivers of eligible children.
- Conditions
- Mortality, Resistance Bacterial, Child, Only
- Being tested
- Azithromycin, Placebo
- 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.
AzithromycinDrug
Also called Zithromax
Azithromycin will be administered as a directly observed dose in oral suspension form for children:
- Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
- For children 1-11 months of age, weight or age-based dosing will be used
- For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program
PlaceboOther
Placebo will be administered as a directly observed dose in oral suspension form for children:
- Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
- For children 1-11 months of age, weight-based dosing will be used
- For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program
| Study group | Role | What they receive |
|---|---|---|
| Azithro 1-11 | Active comparator | Biannual weight- or height-based dose of oral azithromycin suspension to children 1-11 months old and oral placebo or no intervention to children 12-59 months old Receives: Drug: Azithromycin; Other: Placebo |
| Azithro 1-59 | Active comparator | Biannual age, weight- or height-based dose of oral azithromycin suspension to children 1-59 months old Receives: Drug: Azithromycin |
| Placebo | Placebo comparator | Biannual weight- or height-based dose of oral placebo to children 1-59 months old Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause Mortality (1-59 Months Old)
Mortality rate (deaths per 1,000 person-years at risk) among children 1-59 months of age, comparing the azithro 1-59 and placebo arms.
Measured: from 6 months up to 2.5 years
All-cause Mortality (1-11 Months Old)
Mortality rate (deaths per 1,000 person-years at risk) among children 1-11 months of age, comparing the azithro 1-11 and placebo arms.
Measured: from 6 months up to 2.5 years
All-cause Mortality (12-59 Months Old)
Mortality rate (deaths per 1,000 person-years at risk) among children 12-59 months of age with rates compared between azithro 1-11 and azithro 1-59 communities.
Measured: from 6 months up to 2.5 years
Prevalence of Resistance to Macrolides - Nasopharyngeal Swabs (1-59 Months Old)
Prevalence of macrolide resistance among pneumococcus-positive nasopharyngeal swabs collected from children aged 1-59 months after 4 distributions. Resistance was assessed among culture-positive pneumococcal isolates from nasopharyngeal swabs.
Measured: After 4 distributions (approximately 24 months)
Load of Genetic Determinants of Resistance to Macrolides - Rectal Swabs (1-59 Months Old)
Community-level load of macrolide antimicrobial resistance determinants in pooled rectal swabs collected from children aged 1-59 months after four biannual distributions. Rectal swabs from each community were pooled and analyzed using metagenomic DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts.
Measured: After 4 distributions (approximately 24 months)
Secondary outcomes (4)
Mortality Rate by Weight-for-age Z-score Subgroup Among Infants Aged 1-11 Months
All-cause mortality incidence rate among children aged 1-11 months who had weight measured during at least one census round and had a valid weight-for-age z-score calculated using the World Health Organization Child Growth Standards. Nutritional status was assessed at the beginning of each census interval. This measure reports the overall mortality rate for this analysis population by randomized treatment arm and is not stratified by weight-for-age z-score subgroup. Mortality rates are reported as deaths per 1,000 person-years.
Measured: After 4 distributions (approximatively 24 month after first distribution)
Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Guardians
Community-level loads of macrolide antimicrobial resistance determinants in nasopharyngeal swabs collected from guardians of children eligible for treatment after four biannual distributions. Nasopharyngeal swabs from each community were pooled and analyzed using DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts; log-transformed values were used only for inferential statistical analyses.
Measured: After 4 distributions (approximatively 24 month after first distribution)
Program Costs Per Dose Delivered
Program cost per dose delivered was estimated using routine administrative data and micro-costing activities. Costs were calculated per dose delivered and were not stratified by randomized treatment arm.
Measured: 1 year
Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Children Aged 7-12 Years
Community-level loads of macrolide antimicrobial resistance determinants in nasopharyngeal swabs collected from children aged 7-12 years after four biannual distributions. Nasopharyngeal swabs from each community were pooled and analyzed using DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts; log-transformed values were used only for inferential statistical analyses.
Measured: After 4 distributions, approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start24 Nov 2020
- Primary completion31 Jul 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)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 AVENIR mortality/resistance trial is a large simple double-masked cluster-randomized trial with response-adaptive allocation in Niger.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 864,493 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Ministry of Health, Niger
- Responsible party
- Sponsor
- Investigators
- Tom M Lietman, MD, Principal investigator, University of California, San FranciscoKieran S O'Brien, PhD, MPH, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04224987
- Sponsor's protocol ID
- 19-28387A
- Acronym
- AVENIR
- Status last verified
- Jul 2026
- First submitted
- 17 Dec 2019
- Last updated
- 6 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- 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
Keenan 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, Arzika AM, Hinterwirth A, Maliki R, Zhong L, Cummings S, Sarkar S, Chen C, Porco TC, Keenan JD, Lietman TM; MORDOR Study Group. Macrolide Resistance in MORDOR I - A Cluster-Randomized Trial in Niger. N Engl J Med. 2019 Jun 6;380(23):2271-2273. doi: 10.1056/NEJMc1901535. No abstract available.
PubMed 31167060Keenan JD, Arzika AM, Maliki R, Boubacar N, Elh Adamou S, Moussa Ali M, Cook C, Lebas E, Lin Y, Ray KJ, O'Brien KS, Doan T, Oldenburg CE, Callahan EK, Emerson PM, Porco TC, Lietman TM. Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa. N Engl J Med. 2019 Jun 6;380(23):2207-2214. doi: 10.1056/NEJMoa1817213.
PubMed 31167050WHO 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 32924384Oldenburg CE, Arzika AM, Maliki R, Lin Y, O'Brien KS, Keenan JD, Lietman TM, For The Mordor Study Group. Optimizing the Number of Child Deaths Averted with Mass Azithromycin Distribution. Am J Trop Med Hyg. 2020 Sep;103(3):1308-1310. doi: 10.4269/ajtmh.19-0328.
PubMed 32067626Peterson B, Arzika AM, Maliki R, Amza A, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Lebas E, Liu Z, Brandt C, Colby E, Oldenburg CE, Porco TC, Arnold BF, Lietman TM, O'Brien KS. Predictors of home- vs. facility-based delivery among women living in rural Niger: a cross-sectional survey within the AVENIR cluster-randomised trial. J Glob Health. 2026 May 22;16:04167. doi: 10.7189/jogh.16.04167.
PubMed 42170714Doan T, Yan D, Arzika AM, Abdou A, Maliki R, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Zhong L, Chen C, Liu Y, Yu D, Abraham T, Cheng AS, Peterson B, Oldenburg CE, Porco TC, Arnold BF, Hinterwirth A, Lebas E, O'Brien KS, Lietman TM. Mass azithromycin distribution and antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial. Nat Med. 2026 Mar;32(3):859-868. doi: 10.1038/s41591-026-04217-9. Epub 2026 Mar 17.
PubMed 41845058Arzika AM, Amza A, Maliki R, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Brandt C, Lebas E, Peterson B, Liu Z, Oldenburg CE, Doan T, Porco TC, Arnold BF, Lietman TM, O'Brien KS. Spillover of Azithromycin Mass Drug Administration and Child Survival: A Secondary Analysis of a Cluster-Randomized Clinical Trial. JAMA Netw Open. 2025 Jul 1;8(7):e2519693. doi: 10.1001/jamanetworkopen.2025.19693.
PubMed 40638118Peterson B, Arzika A, Maliki R, Abdou A, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Lebas E, Liu Z, Brandt C, Colby E, Oldenburg CE, Porco TC, Arnold B, Lietman TM, O'Brien KS. Mass distribution of azithromycin and child mortality among underweight infants in rural Niger: a subgroup analysis of the AVENIR cluster-randomised trial. BMJ Open. 2025 Mar 27;15(3):e097916. doi: 10.1136/bmjopen-2024-097916.
PubMed 40147984O'Brien KS, Arzika AM, Amza A, Maliki R, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Lebas E, Peterson B, Liu Z, Le V, Colby E, Doan T, Keenan JD, Oldenburg CE, Porco TC, Arnold BF, Lietman TM; AVENIR study group. Azithromycin to Reduce Mortality - An Adaptive Cluster-Randomized Trial. N Engl J Med. 2024 Aug 22;391(8):699-709. doi: 10.1056/NEJMoa2312093.
PubMed 39167806O'Brien KS, Arzika AM, Amza A, Maliki R, Ousmane S, Kadri B, Nassirou B, Mankara AK, Harouna AN, Colby E, Lebas E, Liu Z, Le V, Nguyen W, Keenan JD, Oldenburg CE, Porco TC, Doan T, Arnold BF, Lietman TM; AVENIR Study Group. Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR). BMC Public Health. 2021 Apr 29;21(1):822. doi: 10.1186/s12889-021-10824-7.
PubMed 33926403