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| Name | Class |
|---|---|
| Bill and Melinda Gates Foundation | OTHER |
| Johns Hopkins University | OTHER |
| London School of Hygiene and Tropical Medicine | OTHER |
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Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood mortality. We propose a single multi-site (multi-country), cluster-randomized trial comparing communities randomized to oral azithromycin with those randomized to placebo. We hypothesize that mass azithromycin treatments will reduce childhood mortality.
We will assess childhood mortality over three years, comparing communities where children aged 1-60 months receive biannual oral azithromycin ("Azithromycin" arm) for two years, to communities where the children receive biannual oral placebo ("Control" arm) for two years. During the third year at the Niger site only, everyone will receive azithromycin.
This is a cluster-randomized trial; at each site, communities within a contiguous area of 300,000 to 600,000 individuals will be randomized to azithromycin or placebo using simple random sampling.
Niger contingency study: In the event that mass distributions of oral azithromycin are proven to reduce mortality in 1-60 month-old children, then we will treat all communities in Niger with mass azithromycin distributions to test whether the intervention continues to reduce childhood mortality after the initial 2 years of mass treatments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Biannual mass oral azithromycin | Active Comparator | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
|
| Biannual mass oral placebo | Placebo Comparator | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years In Niger during year 3, all communities will be offered azithroymcin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin | Drug | Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause Mortality Rate in Children Aged 1-60 Months | This is a single multi-site trial, with each country as a secondary analysis. Also, an interim analysis of efficacy and futility will be conducted according to a pre-specified plan in the Statistical Analysis Plan. | 24 Months |
| All-cause Mortality Rate in Children Aged 1-60 Months | This was a pre-specified contingency study in Niger only in which all communities were treated with mass azithromycin during the third year of the study following the primary 24-month endpoint. | 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only) | Deaths were assessed via biannual population census. A pre-specified outcome was cause of death, assessed by verbal autopsy. | 24 Months |
| Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death |
Not provided
Inclusion Criteria:
Communities
Individuals - All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census.
Exclusion Criteria:
Individuals
- Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)
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| Name | Affiliation | Role |
|---|---|---|
| Tom M Lietman, MD | University of California, San Francisco | Principal Investigator |
| Elodie J Lebas, RN | University of California, San Francisco | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Proctor Foundation | San Francisco | California | 94143 | United States | ||
| Johns Hopkins University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41432154 | Derived | Hinterwirth A, Chen C, Yan D, Zhong L, Zhou Z, Liu Y, Keenan J, O'Brien KS, Lebas E, Porco TC, Lietman TM, Doan T. Co-selection of genetic antibiotic resistance in Streptococcus pneumoniae after repeated azithromycin mass drug administrations in Niger. Antimicrob Agents Chemother. 2026 Feb 4;70(2):e0156225. doi: 10.1128/aac.01562-25. Epub 2025 Dec 23. | |
| 38739754 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Biannual Mass Oral Azithromycin | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
| FG001 | Biannual Mass Oral Placebo | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years In Niger during year 3, all communities will be offered azithroymcin. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MORDOR Stage I Year 1-2 |
| |||||||||||||
| MORDOR Stage II Year 3 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Biannual Mass Oral Azithromycin | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | All-cause Mortality Rate in Children Aged 1-60 Months | This is a single multi-site trial, with each country as a secondary analysis. Also, an interim analysis of efficacy and futility will be conducted according to a pre-specified plan in the Statistical Analysis Plan. | Posted | Number | deaths per 1000 person-years | 24 Months |
|
36 months.
A SAE is any adverse event that:
Or that is considered to be:
· An important medical event
SAE reporting excludes mortality as measured for the primary outcome.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Biannual Mass Oral Azithromycin | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suspected ileus | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ying Lin | UCSF F.I. Proctor Foundation | 4155144709 | ying.lin@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2018 | Jul 31, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 15, 2019 | Jul 24, 2019 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D007239 | Infections |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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|
| Placebo | Drug | Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
|
Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death during the 24 month phase |
| 24 months |
| All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children | We recorded clinic visits one year prior the study and during the first year of the study and collected outcomes of these visit. | 24 months |
| Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only) | At 6-monthly intervals a census of the communities was conducted, and for child deaths a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. Mortality due to pneumonia or diarrhea by age group and arm are shown in the outcome measure data table below. | 24 Months |
| Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only) | Cause-specific mortality by intention-to-treat for the four main inferred causes of death in the study area. | 24 Months |
| Baltimore |
| Maryland |
| 21205 |
| United States |
| College of Medicine at the University of Malawi, Blantyre | Blantyre | Malawi |
| The Carter Center, Niger | Niamey | Niger |
| Kongwa Trachoma Project | Kongwa | Tanzania |
| London School of Hygiene & Tropical Medicine | London | United Kingdom |
| Peterson B, Arzika AM, Amza A, Maliki R, Karamba AM, Moussa M, Kemago M, Liu Z, Houpt E, Liu J, Pholwat S, Doan T, Porco TC, Keenan JD, Lietman TM, O'Brien KS. Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial. Clin Infect Dis. 2024 Nov 22;79(5):1136-1143. doi: 10.1093/cid/ciae267. |
| 38709718 | Derived | Arzika AM, Abdou A, Maliki R, Beido N, Kadri B, Harouna AN, Galo AN, Alio MK, Lebas E, Oldenburg CE, O'Brien KS, Chen C, Zhong L, Zhou Z, Yan D, Hinterwirth A, Keenan JD, Porco TC, Lietman TM, Doan T; MORDOR Study Group. Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR). PLoS Med. 2024 May 6;21(5):e1004386. doi: 10.1371/journal.pmed.1004386. eCollection 2024 May. |
| 38100110 | Derived | Chao 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. |
| 34991704 | Derived | Pickering H, Hart JD, Burr S, Stabler R, Maleta K, Kalua K, Bailey RL, Holland MJ. Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome in children: a randomized, controlled trial. Gut Pathog. 2022 Jan 6;14(1):5. doi: 10.1186/s13099-021-00478-6. |
| 34037753 | Derived | Arzika AM, Maliki R, Abdou A, Mankara AK, Harouna AN, Cook C, Hinterwirth A, Worden L, Zhong L, Chen C, Ruder K, Zhou Z, Lebas E, O'Brien KS, Oldenburg CE, Le V, Arnold BF, Porco TC, Keenan JD, Lietman TM, Doan T. Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial. Clin Infect Dis. 2021 Oct 5;73(7):1292-1295. doi: 10.1093/cid/ciab485. |
| 33176084 | Derived | Doan 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. |
| 32931496 | Derived | O'Brien KS, Arzika AM, Maliki R, Manzo F, Mamkara AK, Lebas E, Cook C, Bailey RL, West SK, Oldenburg CE, Porco TC, Arnold B, Keenan JD, Lietman TM; MORDOR Study Group. Biannual azithromycin distribution and child mortality among malnourished children: A subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med. 2020 Sep 15;17(9):e1003285. doi: 10.1371/journal.pmed.1003285. eCollection 2020 Sep. |
| 32426812 | Derived | Doan T, Hinterwirth A, Arzika AM, Worden L, Chen C, Zhong L, Oldenburg CE, Keenan JD, Lietman TM. Reduction of Coronavirus Burden With Mass Azithromycin Distribution. Clin Infect Dis. 2020 Nov 19;71(16):2282-2284. doi: 10.1093/cid/ciaa606. |
| 31981558 | Derived | Keenan 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. |
| 31443654 | Derived | Bloch EM, Munoz B, Mrango Z, Weaver J, Mboera LEG, Lietman TM, Sullivan DJ Jr, West SK. The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study. Malar J. 2019 Aug 23;18(1):284. doi: 10.1186/s12936-019-2914-8. |
| 31167060 | Derived | Doan 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. |
| 31167050 | Derived | Keenan 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. |
| 30561577 | Derived | Porco TC, Hart J, Arzika AM, Weaver J, Kalua K, Mrango Z, Cotter SY, Stoller NE, O'Brien KS, Fry DM, Vanderschelden B, Oldenburg CE, West SK, Bailey RL, Keenan JD, Lietman TM; Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) Study Group. Mass Oral Azithromycin for Childhood Mortality: Timing of Death After Distribution in the MORDOR Trial. Clin Infect Dis. 2019 May 30;68(12):2114-2116. doi: 10.1093/cid/ciy973. |
| 29694816 | Derived | 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. |
| 25858004 | Derived | Porco TC, Stoller NE, Keenan JD, Bailey RL, Lietman TM. Public key cryptography for quality assurance in randomization for clinical trials. Contemp Clin Trials. 2015 May;42:167-8. doi: 10.1016/j.cct.2015.03.016. Epub 2015 Apr 7. No abstract available. |
| NOT COMPLETED |
|
| BG001 | Biannual Mass Oral Placebo | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years In Niger during year 3, all communities will be offered azithroymcin. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Number of communities | Number | communities |
|
| OG001 | Biannual Mass Oral Placebo | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years In Niger during year 3, all communities will be offered azithroymcin. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. |
|
|
| Primary | All-cause Mortality Rate in Children Aged 1-60 Months | This was a pre-specified contingency study in Niger only in which all communities were treated with mass azithromycin during the third year of the study following the primary 24-month endpoint. | Posted | Number | 95% Confidence Interval | deaths per 1000 person-years | 36 months |
|
|
|
| Secondary | Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only) | Deaths were assessed via biannual population census. A pre-specified outcome was cause of death, assessed by verbal autopsy. | Posted | Number | 95% Confidence Interval | Deaths per 1000 person years | 24 Months |
|
|
|
| Secondary | Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death | Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death during the 24 month phase | all children 1-59 months treated | Posted | Mean | 95% Confidence Interval | usd per death averted | 24 months |
|
|
|
| Secondary | All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children | We recorded clinic visits one year prior the study and during the first year of the study and collected outcomes of these visit. | Number of children visiting health centers | Posted | Number | post-treatment clinical visits | 24 months |
|
|
|
| Secondary | Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only) | At 6-monthly intervals a census of the communities was conducted, and for child deaths a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. Mortality due to pneumonia or diarrhea by age group and arm are shown in the outcome measure data table below. | Posted | Number | deaths per 100 person-years | 24 Months |
|
|
|
| Secondary | Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only) | Cause-specific mortality by intention-to-treat for the four main inferred causes of death in the study area. | Posted | Number | 95% Confidence Interval | deaths per 1000 person-years | 24 Months |
|
|
|
| 3,262 |
| 97,047 |
| 3,273 |
| 97,047 |
| 0 |
| 97,047 |
| EG001 | Biannual Mass Oral Placebo | Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years In Niger during year 3, all communities will be offered azithroymcin. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin. | 3,392 | 93,191 | 3,400 | 93,191 | 0 | 93,191 |
| Suspected dehydration | General disorders | Systematic Assessment |
|
| Malaria | Infections and infestations | Systematic Assessment |
|
| Coma | General disorders | Systematic Assessment |
|
| ARI | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| General disorders | Systematic Assessment |
|
| Death | General disorders | Systematic Assessment |
|
Not provided
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| Organic Chemicals |
| AIDS |
|
| Measles |
|
| Meningitis |
|
| Dysentery |
|
| Diarrhea |
|
| Pertussis |
|
| Pneumonia |
|
| Malaria |
|
| Hemorrhagic fever |
|
| Other infection |
|
| Unspecified |
|
| Total |
|
| Age group Mortality: 12 - 23 months |
|
| Age group Mortality: 24 - 59 months |
|
| HIV/AIDS |
|
| Diarrhoea |
|